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INTRAMURAL RESEARCH AWARD WINNERS | ||||||
Dr. Castle, a Cancer Prevention fellow in the Environmental Epidemiology Branch, submitted a proposal to evaluate cytokine profiles in cervical secretions and determine their relationship to human papillomavirus (HPV) persistence and progression to neoplasia. Persistent HPV infections are the central cause of cervical cancer and its precursor lesion, high-grade cervical intraepithelial neoplasia (CIN). Most HPV infections, however, do not progress to high-grade CIN or cancer; instead, they tend to become inapparent within a year. The immune response to HPV infection is the most important known determinant of HPV persistence and, therefore, of cancer risk. Dr. Castle will use recycling immunoaffinity chromatography, an emerging technology for simultaneous ultramicroanalysis of multiple analytes in biologic fluids, to examine cytokines in cervical secretions collected from women participating in a prospective cohort study in Costa Rica. He will evaluate potential associations between baseline cytokine profiles and the risk of HPV progression to high-grade CIN. Dr. Anneclaire DeRoos and Dr. Erin Bell, of the Occupational Epidemiology Branch, intend to investigate the relationship of immunological biomarkers and the risk of non-Hodgkin's lymphoma (NHL). Populations with profound alterations in the immune system, such as organ transplant recipients and persons with HIV, are prone to NHL. Conditions with milder alterations have also been linked to NHL, but with inconsistent results. Drs. DeRoos and Bell propose a case-control study of NHL nested within a prospective cohort study of Northern California Kaiser Permanente members to assess cytokines, chemokines, and immunoglobulins in prediagnostic sera as risk factors for NHL. In the Nutritional Epidemiology Branch, Dr. Andrew Flood and Dr. Volker Mai will investigate whether dietary patterns associated with high glycemic load play a role in the etiology of colorectal polyps. Using data and blood samples from the Polyp Prevention Trial, they will develop an index of glycemic load on the basis of food frequency questionnaire data; assess the relationship of the index with blood measures of insulin, c-peptide, glucose, and insulin-like growth factor and its binding protein; and evaluate the index and blood measures in relation to polyp recurrence. Dr. Mary Lou McMaster, of the Genetic Epidemiology Branch, plans to examine familial aspects of Waldenström's macroglobulinemia by combining clinical, epidemiologic, and laboratory approaches. Dr. McMaster plans to assemble a large group of patients with familial Waldenström's macroglobulinemia to determine clinical and laboratory manifestations and to search for associations with candidate genes that may contribute to susceptibility. In the IRA program, tenure-track investigators and fellows within the Division apply for funds (up to $75,000 per year, renewable for up to three years) for small projects that cross the usual organizational boundaries. Each proposal is reviewed by a member of the NCI Board of Scientific Counselors or another scientist from outside NIH with appropriate expertise, plus a senior scientist within DCEG. The proposals are judged with respect to their potential for significant scientific or public health impact, innovative aspects of the approach or methodology, interdisciplinary nature of the project (especially in using collaborative links with other research groups), ability to achieve the objectives within the proposed time frame and resources, and programmatic relevance to the mission of our Division. The award can be combined with money from other sources to fund a larger project. Eligibility for IRAs has changed over time. In 1998, when the IRA program began, tenured and tenure-track principal investigators could receive support for new initiatives through this mechanism. In 1999, pre- and postdoctoral fellows in DCEG also became eligible to apply for IRAs. The most recent change occurred this year; the program was opened to tenure-track investigators and to fellows in DCEG, but not to tenured investigators. We believe that nontenured scientists, who often go on to apply for positions outside of NIH, can benefit the most from documented success in obtaining funding through a competitive mechanism. More information on the IRA program can be found at the DCEG web site.
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THE ALARMING INCREASE IN ESOPHAGEAL ADENOCARCINOMAS |
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One of the great advantages of using the Surveillance, Epidemiology, and End Results (SEER) program to keep close tabs on cancer incidence in the United States is the ability to identify trends early. SEER data have revealed that the incidence of adenocarcinoma of the esophagus has risen more than 350 percent among white men over the past two decades, increasing more rapidly than any other type of cancer. The rate among white men is much higher than that among white women or among black men and women, although incidence is increasing in these groups as well. Dr. Susan Devesa, Chief of the Descriptive Studies Section in the Biostatistics Branch, looked at the incidence patterns of this cancer and observed that from 1974 through 1997, the incidence of esophageal adenocarcinoma increased at a rate of 8.8 percent annually for white men and 8.3 percent annually for white women. Dr. Devesa pointed out that among white men, the incidence rate for esophageal adenocarcinoma surpassed that for squamous cell carcinoma of the esophagus in 1990. Any rise in the rate of esophageal cancer is alarming because the disease is notoriously difficult to identify early enough and treat effectively. Because the prognosis for esophageal cancer is so poor, it is obviously far better to prevent the disease before it develops.
"In adenocarcinoma, 95 percent arise in the lower third of the esophagus, where acid reflux is likely to occur," said Dr. Chow. In contrast, "with squamous cell carcinoma, we see the tumors distributed rather evenly along the entire length of the esophagus." Dr. Chow added that cancers of the gastric cardia, the area of the stomach closest to the esophagus, are also occurring more frequently, whereas tumors in other parts of the stomach are steadily declining. Even though the sequence of reflux disease, Barrett's esophagus, and esophageal adenocarcinoma is well established, the cause of the rise in reflux disease is less clear. One risk factor may be obesity. The multicenter case-control study revealed a strong association of adenocarcinoma with being overweight, an increasingly prevalent condition in the U.S. population. "How obesity increases the risk of this cancer hasn't been fully explored, but it may act by contributing to reflux," said Dr. Fraumeni. "Perhaps the mechanical pressure from abdominal obesity forces the stomach contents to reflux through the lower esophageal sphincter." Dr. Chow noted that the research team is also investigating the role of dietary factors, but analyses have not been completed. The study also looked for a relationship between risk of adenocarcinoma and medications that relax the esophageal sphincter. Results revealed a possible association with asthma medications, but asthma itself is associated with acid reflux. No correlation was found with drugs used to treat reflux, such as histamine-2 antagonists, but a protective effect from the use of nonsteroidal anti-inflammatory drugs (NSAIDs) was reported by researchers at the University of Washington. Cigarette smoking was identified as another causal factor of esophageal adenocarcinoma, although the risk was less pronounced than that observed for squamous cell cancer of the esophagus. The risk for developing lung cancer or squamous tumors of the esophagus drops soon after smoking cessation, but the risk for esophageal adenocarcinoma remains high for at least 30 years among ex-smokers. "These findings suggest a long latency period for this tumor, with smoking having an early-stage effect," Dr. Fraumeni said. "If that is the case, the upward trend in incidence may partly reflect the smoking habits of 30 years ago." Dr. Chow also noted an inverse relation seen with esophageal adenocarcinoma and a virulent strain of Helicobacter pylori, the main cause of peptic ulcer and most likely gastric cancer. The frequency of H. pylori infection is declining in the population, unlike that of acid reflux or Barrett's esophagus. "How this bacteria might protect against this tumor is not clear," Dr. Fraumeni said. "But the findings are consistent with the hypothesis developed by our collaborator, Dr. Martin Blaser of New York University, who reasoned that the colonization of gastric mucosa by Helicobacter organisms may inhibit the production of gastric acid that can reflux into the esophagus, and that eradicating the infection may increase acid secretion and reflux." Whatever the contributing factors are, the treatment options available
once esophageal adenocarcinoma has been diagnosed are not particularly
effective. Dr. Fraumeni noted that increasing attention is being paid
to developing preventive measures and guidelines of medical practice
aimed at Barrett's esophagus, the key precursor lesion. Toward this
end, NCI and the National Institute of Diabetes and Digestive and Kidney
Diseases are hosting a series of workshops designed to address the etiology,
prevention, clinical management, biologic markers, and other research
issues associated with Barrett's esophagus. One focus will be on the
use of chemopreventive agents such as NSAIDs known as COX-2 inhibitors,
as well as novel diagnostic and therapeutic approaches. |
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DCEG RESEARCH ON HORMONES AND BREAST CANCER | ||||||
A quarter-century ago, Dr. Robert Hoover, Director of the Epidemiology and Biostatistics Program (EBP), became the first investigator to link long-term use of menopausal "replacement" estrogens to increased breast cancer risk in a retrospective cohort study. Over 10 years ago, Dr. Hoover and Dr. Catherine Schairer, in collaboration with Swedish researchers, were the first to report that adding progestins to estrogen replacement therapy might increase risk beyond that imposed by estrogen, results that were subsequently confirmed. Ironically, hormone replacement therapy has also been linked to reduced breast cancer mortality. One explanation is that breast cancers are diagnosed earlier in hormone users because of surveillance, but Dr. Schairer, using data from the Breast Cancer Detection Demonstration Project follow-up study, found this was not the case. Current analyses seek to determine whether replacement therapy is associated with risk of tumors that have more favorable characteristics. The relationship between oral contraceptives, which contain a fixed amount of estrogen and progestin, and breast cancer has been studied by several DCEG researchers, particularly EEB's Dr. Louise Brinton. An early study among participants in the Breast Cancer Detection Demonstration Project showed no overall association between oral contraceptives and breast cancer, which accords with prevailing opinion today. Research continues in this area, however, and various DCEG initiatives have expanded relevant knowledge. For example, in a study of young women the strongest link with oral contraceptives was found in cancers diagnosed before women had turned age 35. Other research indicates that women who use both oral contraceptives and menopausal hormones may be at particularly high risk and that the oncogene HER-2/neu might be linked with oral contraceptives in some important way. Specifically, risk of breast cancer in relation to oral contraceptive use varied with HER-2/neu status, with the odds ratios for tumors that overexpress this oncogene being twice that for tumors that did not. Conceivably, HER-2/neu is the mechanism by which oral contraceptives affect breast cancer risk, or perhaps it interacts with cofactors in producing the disease. Diethylstilbestrol (DES), a nonsteroidal estrogen first synthesized in 1938 and once widely used to prevent threatened abortion and premature labor, has been studied extensively in recent decades because of its known carcinogenicity. In 1992, NCI, in collaboration with five clinical centers, began a long-term study on DES (currently led by Dr. Robert Hoover and by Dr. Rebecca Troisi of the EBP), with one primary goal being to measure incidence and mortality of cancer, especially of the breast and reproductive system. In 1998, EBP's Dr. Elizabeth Hatch, who formerly led the project, reported that breast cancer incidence in DES-exposed daughters was not elevated. A prospective study of women who had donated blood samples for a breast cancer study has provided rich opportunities for research. In one study, Dr. Joanne Dorgan, formerly of EEB, reported that in postmenopausal women higher endogenous levels of estradiol, testosterone, and possibly dehydroepiandrosterone independently increased risk of breast cancer. Elsewhere, EEB's Ms. Roni Falk, using controls from a study of Asian American women, found that blood levels of estrogens and sex hormone-binding globulin did not differ between women born in Asia and those born in the United States, but that women born in the United States had consistently lower androgen levels than those born in Asia (U.S.-born women have a higher breast cancer risk). Ms. Patricia Madigan, also of EEB, found that among postmenopausal women, some reproductive and lifestyle factors may be mediated, in part, through increased endogenous hormone levels. Some of the current research at DCEG may yield great benefits for researchers elsewhere who are interested in studying breast cancer. For example, EEB's Dr. Xia Xu is developing liquid chromatography/mass spectroscopy methods to measure steroid hormones, hormone metabolites, and phytoestrogens in a single run in urine, blood, and ultimately tissue samples; these methods will require only small sample volumes. In addition, Dr. Ruthann Giusti, of the Clinical Genetics Branch, is exploring methods to measure hormones in breast duct lavage fluid obtained from women carrying mutations in the BRCA1 and BRCA2 genes. In studies currently under way, DCEG researchers are taking a variety of approaches to further our understanding of the link between hormones and breast cancer. For example, a study is under way to understand how hormone levels in umbilical cord blood are associated with characteristics related to cancer risk in offspring; another is assessing the effects of moderate alcohol intake on endogenous hormone levels. Research with a heavy genetic emphasis is also ongoing—case-control studies in the United States and Poland, for example, are investigating polymorphisms in genes involved in the production, metabolism, and bioavailability of sex hormones in relation to breast cancer risk. In cross-sectional studies of premenopausal women, serum sex hormone levels are being examined in relation to polymorphism in these same genes. Another study is designed to determine whether there are genetically identifable subsets of women who are more or less likely to benefit from tamoxifen as a prophylactic measure against breast cancer. This brief summary illustrates not only the wide range of investigation
by DCEG researchers but also the complexity of breast cancer as an etiologic
puzzle and the many avenues by which it can be approached. Studies ranging
from traditional questionnaires to laboratory investigations incorporating
the most current molecular techniques may provide important information
useful for prevention, screening, and perhaps treatment as well. |
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FUTURE DIRECTIONS AND EXTENSIONS OF THE GAIL MODEL | ||||||
The Gail model is primarily used to counsel women about their risk of breast cancer over various age intervals. The model was developed for this purpose at the request of Dr. John Mulvihill, a former member of NCI's Clinical Epidemiology Branch, who needed this information to advise patients in an NCI clinic who were at high risk of breast cancer. The model has also proven useful for planning clinical trials, such as BCPT, because the power of such studies depends on a reflection of average absolute risk, or the number of breast cancers that develop over the course of the trial. Using this model to identify women at high absolute risk can also inform clinical management. A woman at high absolute risk of breast cancer may benefit more from tamoxifen, other things being equal, than a woman at lower risk of breast cancer, because for the latter the toxicities of tamoxifen can outweigh the benefits. Likewise, a woman in her 40's may be influenced to begin regular mammographic screening if her absolute risk is equivalent to that of a 50-year-old woman. Although the Gail model has been validated for white women, it needs
to be validated and, if necessary, modified for African American women,
Hispanic women, and other subgroups. Indeed, some evidence suggests
that the model underestimates risk in African American women, for whom
BCDDP data on attributable risk are sparse. Investigators conducting
population-based case-control studies and cohort studies in minority
populations can contribute data to test and improve the model. Incorporating
stronger predictors can also improve the Gail model, although it predicts
risk accurately on average. Members of the Biostatistics Branch are
currently conducting reliability studies and other analyses to determine
whether the percentage of dense tissue on a mammogram can be used to
strengthen the model. Other potential predictors include molecular or
cytological markers from nipple aspirates and genetic predictors. Models
that depend only on features of the medical and family history will
probably remain useful, however, and can guide decisions regarding the
need for more invasive studies to evaluate risk. |
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DR. BLANCHE ALTER, CANCER EXPERT | ||||||
DCEG Linkage caught up with Dr. Alter to talk about her plans now that she has joined CGB as a cancer expert. Why did you choose to go back to school rather than simply look for another position? I decided to explore ways in which my clinical and laboratory experiences in hematology and oncology might be used in a different and challenging manner. I started looking online at catalogs for schools of public health and discovered I was very interested in all the courses, particularly biostatistics, cancer, and genetic epidemiology. Many of the clinical reviews I had done of rare hematologic syndromes were really epidemiologic in their focus. How did you decide to take your course work at Johns Hopkins University School of Public Health? I have a history with Johns Hopkins. Although I did my undergraduate and specialty work in Boston at Radcliffe College and later at Harvard Medical School, I received my medical degree and my pediatric training at Johns Hopkins University. Most of the people I respected told me to go to Johns Hopkins University School of Public Health. One of the faculty there shared my interest in cancer progression in patients with genetic hematologic diseases. Unfortunately, he left shortly after I arrived! Did you have to change your plans and find a new advisor? No. That person had several graduate students and came back to Hopkins to meet with them. I'm here at NCI because of a collaboration with Dr. Mark Greene, Chief of CGB. For my project at Johns Hopkins, I studied patients with Fanconi's anemia. Because medicine has improved our management of their usual problem, aplastic anemia, we've discovered that these patients are living long enough to get specific types of cancer at unusually early ages. But my interest goes beyond patients with Fanconi's anemia. Patients with a number of different "benign" hematologic diseases are at an increased risk for cancer as they get older. We're seeing that we can predict the types of cancer they're likely to get. Here at NCI, I plan to explore this propensity for cancer in patients thought to have these so-called benign diseases. Do you mean these patients are likely to get other blood-related cancers as they get older? They get leukemia, but they are likely to get solid tumors as well. For example, Fanconi's anemia arises from a defect in DNA repair. Patients who have Fanconi's anemia are at risk of getting aplastic anemia, acute myeloid leukemia, oropharyngeal and esophageal cancers, and gynecologic cancers like cervical and vulvar cancer. But it's not quite that simple. Sometimes the bone marrow disease in these patients is cured because they've undergone bone marrow transplantation. We have to look at what roles immunosuppression and graft-versus-host disease may play in the development of these cancers. In addition, we plan to look at the rest of the families to establish the cancer risk among heterozygotes. Are these patients more susceptible to human papillomavirus infection? That's one possibility. We are definitely going to look at viruses and whether they are present in these tumor biopsies. But these cancers can also arise without human papillomavirus infection. Whatever turns out to be true, we are going to learn something about cancer pathways. I'm also looking at patients who have Diamond-Blackfan anemia, a pure red cell aplasia. At least half a dozen of these patients have developed osteogenic sarcoma as well as leukemias and other cancers. Patients with dyskeratosis congenita, an X-linked disorder, often develop oropharyngeal and gastrointestinal cancers similar to patients with Fanconi's anemia. Patients with Shwachman-Diamond syndrome often go on to develop aplastic anemia and leukemia. How far along is your project? I'm still trying to get all the collaborators on board. Our patients
suffer from multisystem diseases. When we bring patients in, many different
specialists will need to meet with them. We also want to perform extensive
laboratory evaluations to understand carcinogenesis in these disorders.
Eventually, we will bring in one new family a week to the Clinical Center
for the study. We also plan a larger study of patients that will not
come to the Clinical Center, but who will provide epidemiologic information
and laboratory and tumor biopsy materials. I am still at the review
stage, which will be followed by full protocol development. |
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KIYOHIKO MABUCHI, CANCER EXPERT |
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What sparked your interest in epidemiology? I became interested in epidemiology while I was studying medicine at the Osaka University Medical School. I was rather disappointed with clinical medicine and became more interested in public health. Epidemiology seemed to be a very rational way of deciphering how disease occurred. What areas of epidemiology did you initially study? I became involved in cancer epidemiology when I was working at the Sloan-Kettering Institute for Cancer Research, where I worked on smoking and lung cancer. Then, I decided to go to Johns Hopkins University School of Hygiene and Public Health for both master's and doctoral degrees in public health and epidemiology. At Johns Hopkins, I did occupational epidemiology studies on a cohort of people who were exposed to arsenic powder in pesticide production. Arsenic exposure had been linked to skin cancer and lung cancer—which is what I worked on. More recently, it's been discovered that arsenic exposure can also cause bladder cancer. After graduation I moved to the University of Maryland School of Medicine as an assistant professor in epidemiology and preventive medicine. Besides teaching, I continued to work on epidemiological studies of cancer while I was there. How did you get involved with studies of the A-bomb survivors? I got the opportunity to spend some time in Hiroshima, and that's when I became interested in radiation epidemiology. As a result of the studies on these A-bomb survivors—probably the largest cohort with radiation exposure with the longest follow-up—we know a lot more about the cancer risks from radiation exposure. The study of the A-bomb cohorts was initiated in the 1950's. This was a fascinating and epidemiologically robust population to study, and the experience gave me a sense of responsibility because of its societal impact. It opened my eyes to science in a way I hadn't known before. What were the advantages of working on this cohort? One of the biggest advantages is that you can get a good estimate of the exposure because of tremendous dosimetry work done over the years. These data have been used to set up worldwide safety standards for radiation exposure. One could say that atomic bomb data has set the standard in radiation health research. Our understanding of radiation effects has evolved over the years. Before we knew of the link with cancer, we thought that radiation accelerated the aging process. Then, it became clear that radiation caused cancer as well as leukemia, possibly through chromosomal and DNA damage. This suggested to us a mechanism for how radiation increased the risk of cancer. We still don't know exactly how radiation causes cancer, but new molecular biological approaches will help us better understand the mechanisms. Now, what's become evident is that after 40 or 50 years, there is an increase in diseases other than cancer—primarily cardiovascular disease—as the cohort ages. Many theories exist for how this happens, but we are only starting to investigate them. It really just shows the importance of how long this study has gone on and how much we can learn from it. The effect of radiation is really quite long-lasting, and we don't really have biological models for it. Why did you decide to leave Hiroshima? Well, I was interested in learning what NCI was doing and thinking about what should be done with the A-bomb studies. It's always good to get fresh ideas, to get a different perspective. I also like the multidisciplinary environment here. I took a sabbatical leave to come here. Last April, I joined the staff. Are you continuing your work with A-bomb survivors? Yes, I plan to. But right now I'm also working with other people in REB on a cohort of 140,000 radiation technologists—mostly women—who've been studied for many years by the Branch. This cohort differs from the A-bomb survivors in that they've received low-level doses over many years. We can address the question of whether health risks from chronic doses are different than those from acute doses of radiation, as biological data suggest. I'd also like to start new studies here on other forms of radiation,
such as ultraviolet exposure and electromagnetic field radiation. These
forms affect the tissues and cells differently than ionizing radiation
does. Working with experts outside REB would provide an exciting opportunity
to learn the biological background of how radiation, together with other
factors, leads to cancer, and to help develop more effective methods
for disease prevention. |
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NEWSLETTER ANNOUNCEMENTS |
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The Clinical Genetics Branch (CGB), headed by Dr. Mark Greene, has published a newsletter entitled "Family Research Matters" for family members involved in the NCI Familial Breast-Ovarian Cancer Study. The newsletter is being distributed to approximately 3,500 family members from the hereditary breast/ovarian kindreds that the Genetic Epidemiology Branch (GEB) has been studying over the past several decades. The intent of the newsletter is to:
Beckwith-Wiedemann Syndrome Pamphlet
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2000 COMBINED FEDERAL CAMPAIGN |
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The 2000 Combined Federal Campaign came to a very successful close in early February. Both NIH and NCI enjoyed a high level of success. NIH raised a total of $1,453,096, of which NCI raised $244,240, which was 108 percent of its dollar goal. NCI also achieved 49 percent participation.
Deserving special recognition and thanks are DCEG's dedicated Branch keyworkers, who selflessly gave their time to ensure the success of the campaign. This year's team consisted of: Dr. Dalsu Baris, Occupational Epidemiology Branch Congratulations and a hearty thanks to all who participated in this
year's campaign. |
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DCEG WELCOMES THE NEW DEAN FOR THE OFFICE OF EDUCATION |
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LABORATORY OF POPULATION GENETICS NEWS |
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The Laboratory of Population Genetics (LPG), headed by Dr. Kenneth Buetow, now has its full complement of five principal investigators.
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RECENT SCIENTIFIC HIGHLIGHTS |
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See page 1 for article on brain cancer and cell phone use. Breast Cancer Tumor Variants in Breast Cancer Patients This study examined breast cancer records from NCI's SEER database for 19,541 white women with node-negative breast cancer to determine tumor cell characteristics and breast cancer-specific survival in relation to estrogen receptor (ER) or progesterone receptor (PR) status. Age frequency density plots with respect to hormone receptor expression showed two overlapping breast cancer populations with early-onset and/or late-onset etiologies. Independent ER+ and PR+ expression was associated with smaller tumor size, better grade, and better cancer-specific survival than was independent ER- or PR- expression. Joint ERPR expression exhibited negative biologic gradients for tumor size, grade, and cancer-specific survival: ER+PR+-->ER+PR--->ER- PR+-->ER-PR-. ER-PR- exhibited the worst phenotypes. (Anderson WF, Chu KC, Chatterjee N, Brawley O, Brinton LA. Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the Surveillance, Epidemiology, and End Results database. J Clin Oncol 2001;19:18-27) Breast Reduction and Breast Cancer Risk In a nested case-control study of 161 breast cancer patients and 483
controls from a Swedish cohort of 31,910 women who had had breast reduction
surgery, researchers collected information on the amount of breast tissue
removed and other factors that influence breast cancer risk. Compared
with subjects that had had at least 1,600 grams of tissue removed from
both breasts, subjects with less than 800 grams removed had an odds
ratio of 0.24. This ratio persisted within each subgroup examined after
data were adjusted for other breast cancer risk factors. This result
should be reassuring to women undergoing either cosmetic breast reduction
or prophylactic mastectomy. (Brinton LA, Persson I,
Boice JD Jr, McLaughlin JK, Fraumeni JF Jr. Breast cancer risk in relation
to amount of tissue removed during breast reduction operations in Sweden.
Cancer 2001;91:478-483) Cervical Cancer Smoking and Cervical Cancer In this multicenter case-control study of 124 adenocarcinoma cervical cancer cases, 139 squamous carcinoma cases, and 307 community controls, 18 percent of adenocarcinoma cases, 43 percent of squamous carcinoma cases, and 22 percent of controls were current smokers. After the study was controlled for human papillomavirus and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (odds ratio [OR] = 0.6, 95 percent CI = 0.3-1.1 for current smokers; OR = 0.7, 95 percent CI = 0.4-1.3 for those who smoked one pack or more per day). Squamous carcinomas were positively associated with smoking (OR = 1.6, 95 percent CI = 0.9-2.9 for current smokers; OR = 1.8, 95 percent CI = 1.0-3.3 for those who smoked one pack or more per day). Although both cervical cancer histologic types are caused by human papillomavirus, etiologic cofactors for these tumors may differ. (Lacey JV, Frisch M, Brinton LA, Abbas FM, Barnes WA, Gravitt PE, Greenberg MD, Greene SM, Hadjimichael OC, McGowan L, Mortel R, Schwartz PE, Zaino RJ, Hildesheim A. Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States). Cancer Causes Control 2001;12:153-161) Human Papillomavirus and Risk of Cervical Cancer A prevalent case-control study within a population-based cohort of 10,000 women in Costa Rica was used to examine the association between human papillomavirus (HPV) type 16 variants and cervical cancer. Host genotyping was performed on a subset of 140 cases—16 cancers; 55 high-grade squamous intraepithelial lesions; and 69 low-grade squamous intraepithelial lesions, equivocal lesions, or normal cytology. The European-derived HPV16 prototype virus (EP[g]) was detected in 36 subjects. Women with high-grade squamous intraepithelial lesions or cancer who tested positive for non-European-like (NE) variants had a risk ratio of 2.7 (95 percent CI = 0.75-9.9) and 11 (95 percent CI = 2.5-50), respectively. No statistically significant association was observed for persons positive for European-like (EL) variants. (Hildesheim A, Schiffman M, Bromley C, Wacholder S, Herrero R, Rodriguez AC, Bratti MC, Sherman ME, Scarpidis U, Lin QQ, Terai M, Bromley RL, Buetow KH, Apple RJ, Burk RD. Human papillomavirus type 16 variants and risk of cervical cancer. J Natl Cancer Inst 2001;93:315-318) ASCUS/LSIL Triage Study The ASCUS/LSIL (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion) Triage Study, a multicenter, randomized trial, compared the sensitivity and specificity of management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3). Among participants with ASCUS, the underlying prevalence of histologically confirmed CIN3 was 5.1 percent. Sensitivity to detect CIN3 or above by testing for cancer-associated human papillomavirus DNA was 96.3 percent, and 56.1 percent of women were referred to colposcopy. Sensitivity of a single repeat cytology specimen with a triage threshold of high-grade squamous intraepithelial lesions or above was 44.1 percent, with 6.9 percent referred, and sensitivity of a lower cytology triage threshold of ASCUS or above was 85.3 percent, with 58.6 percent referred. Testing for cancer associated human papillomavirus DNA among women with ASCUS is a more sensitive and more specific detector for CIN3 or above, compared with a single additional cytologic test indicating ASCUS or above. (Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001;93:293-299) Self-collected Samples in Human Papillomavirus Testing The technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for human papillomavirus (HPV) DNA detection was evaluated. A self-collected swab sample was compared with two clinician-administered swab samples from 111 cases and 157 controls in a case-control study of adenocarcinoma and squamous cell carcinomas of the cervix. The overall agreement between the clinician-administered and self-collected swabs was 88.1 percent (correlation = 0.73). The correlation was highest between the two clinician-administered swabs (0.81). However, the correlation was 0.75 between the self-collected swab and the clinical swab from the ectocervix and 0.67 between those from the endocervix. The type-specific agreement between samples was higher for high-risk, cancer-associated HPV genotypes than for low-risk, noncancer-associated HPV genotypes. The agreement did not vary significantly by age, menopausal status, case status, or clinic center. (Gravitt PE, Lacey JV Jr, Brinton LA, Barnes WA, Kornegay JR, Greenberg MD, Greene SM, Hadjimichael OC, McGowan L, Mortel R, Schwartz PE, Zaino R, Hildesheim A. Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction. Cancer Epidemiol Biomarkers Prev 2001;10:95-100) Clinical Trial for Human Papillomavirus 16 L1 Virus-like Particle Vaccine A double-blind, placebo-controlled dose-escalation trial was performed
to evaluate the safety and immunogenicity of a human papillomavirus
type 16 (HPV16) L1 vaccine, VLP, in healthy adults. The prevaccination
geometric mean ELISA titer for six seropositive individuals was 202
(range, 40-640). Doses of 10 µg or 50 µg were given intramuscularly.
Serum antibody responses at one month after the third injection were
dose dependent in patients who received vaccine without adjuvant or
with MF59 as the adjuvant. When alum was used as the adjuvant, serum
antibody responses were similar at both doses. With the higher dose,
the geometric means of serum ELISA antibody titers to purified VLP were
10,240 (95 percent CI = 1,499-69,938) without adjuvant, 10,240 (95 percent
CI = 1,114-94,145) with MF59 as the adjuvant, and 2,190 (95 percent
CI = 838-5,723) with alum as the adjuvant one month after the third
injection. Responses of subjects within each group were similar. Neutralizing
and ELISA antibody titers were highly correlated (Spearman correlation
= 0.85), which confirmed that ELISA titers are valid proxies for neutralizing
antibodies. The HPV16 L1 VLP vaccine was well tolerated and highly immunogenic
even without adjuvant, and the majority of the recipients achieved serum
antibody titers approximately 40-fold higher than what is observed in
natural infection. (Harro CD, Pang YYS, Roden RBS, Hildesheim
A, Wang ZH, Reynolds MJ, Mast TC, Robinson R, Murphy BR, Karron RA,
Dillner J, Schiller JT, Lowy DR. Safety and immunogenicity trial in
adult volunteers of a human papillomavirus 16 L1 virus-like particle
vaccine. J Natl Cancer Inst 2001;93:284-292) Chordoma Chordoma in the United States Chordoma, a rare tumor arising from notochordal remnants, has been
described to date only by single-institution case series or small population-based
surveys. This study examined data for 400 cases from the Surveillance,
Epidemiology, and End Results (SEER) program, 1973-1995, to measure
incidence and survival patterns for chordoma in the United States. The
overall age-adjusted chordoma incidence rate (IR) per 100,000 was 0.08.
Chordoma was more common in males (IR = 0.10) than in females (IR =
0.06) and rare among blacks and patients aged less than 40 years. Within
the axial skeleton, 32 percent of cases were cranial, 32.8 percent were
spinal, and 29.2 percent were sacral. Cranial presentation was more
likely in younger patients (less than 26 years; p = 0.0001) and
in women (p = 0.037). There was no overall increased risk for
second primary cancers after chordoma. Median survival was 6.29 years;
5- and 10-year relative survival rates were 67.6 percent and 39.9 percent,
respectively. Comparison with other bone sarcomas revealed racial disparities
in incidence for the two developmental tumors, chordoma and Ewing's
sarcoma. (McMaster ML, Goldstein AM, Bromley CM, Ishibe
N, Parry DM. Chordoma: incidence and survival patterns in the United
States, 1973-1995. Cancer Causes Control 2001;12:1-11) Esophageal and Gastric Cancers Relationship between Selenium Levels and Subsequent Cancer Selenium levels in pretrial sera from participants in a randomized nutritional intervention trial in Linxian, China, were used to evaluate the subsequent risk of developing cancer. Serum selenium levels were measured in 590 subjects with esophageal cancer, 402 with gastric cardia cancer, and 87 with gastric noncardia cancer as well as in 1,062 control subjects. Highly significant inverse associations were found with the incidence of esophageal and gastric cardia cancers. The relative risk for comparison of highest with lowest quartile of serum selenium was 0.56 for esophageal cancer and 0.47 for gastric cardia cancer. In the study population, the proportion of these cancers attributable to low selenium levels was 26.4 percent. No evidence was found for a gradient of serum selenium associated with incidence of gastric noncardia cancer. (Mark SD, Qiao YL, Dawsey SM, Wu YP, Katki H, Gunter EW, Fraumeni JF, Blot WJ, Dong ZW, Taylor PR. Prospective study of serum selenium levels and incident esophageal and gastric cancers. J Natl Cancer Inst 2000;92:1753-1763) Risk Factors for Squamous Cell Esophageal Cancer In a population-based case-control study of squamous cell esophageal
cancer among 347 male cases (119 white, 228 black) and 1,354 male controls
(743 white, 611 black), odds ratios of 4.3 (95 percent CI = 2.1-8.7)
for whites and 8.0 (95 percent CI = 4.3-15.0) for blacks were observed
for subjects with annual incomes less than $10,000 compared with those
with incomes of $25,000 or more. The combination of all four major risk
factors—low income, moderate to heavy alcohol intake, tobacco use, and
infrequent consumption of raw fruits and vegetables—accounted for almost
all of the squamous cell esophageal cancers (98 percent for whites and
99 percent for blacks) and for 99 percent of the excess incidence among
black men. (Brown LM, Hoover R, Silverman D, Baris D,
Hayes R, Swanson GM, Schoenberg J, Greenberg R, Liff J, Schwartz A,
Dosemeci M, Pottern L, Fraumeni JF Jr. Excess incidence of squamous
cell esophageal cancer among U.S. black men: role of social class and
other risk factors. Am J Epidemiol 2001;153:114-122) Genetics Cancer in Nordic Ataxia-telangiectasia Patients and Their Families This study in the Nordic countries followed 1,218 blood relatives of 56 patients with ataxia-telangiectasia (A-T), a recessive genetic neurologic disorder caused by mutation of the ATM gene. Among the patients with A-T, six cancers (four leukemias and two non-Hodgkin's lymphomas) were observed compared with 0.16 expected, yielding a standardized incidence ratio (SIR) of 37.5. Among the 1,218 relatives, 150 cancers were recorded, with 126 expected (SIR = 1.1). Invasive breast cancer occurred in 21 female relatives of A-T patients (SIR = 1.5), including 5 of the 50 mothers (all of whom are obligate ATM mutation carriers; SIR = 7.1). Relatives who were less likely to be carriers of a mutant ATM allele had no significant increase in the risk of breast cancer. (Olsen JH, Hahnemann JM, Børresen-Dale A-L, Brøndum-Nielsen K, Hammarström L, Kleinerman R, Kääriäinen H, Lönnqvist T, Sankila R, Seersholm N, Tretli S, Yuen J, Boice JD Jr, Tucker M. Jørgen H. Cancer in patients with ataxia-telangiectasia and in their relatives in the Nordic countries. J Natl Cancer Inst 2001;93:121-127) Hereditary Retinoblastoma and Lung Cancer Risk Survivors of hereditary retinoblastoma are at high risk of dying from a sarcoma, melanoma, or brain tumor attributed to germline mutations in the RB1 gene. Whether these patients are at increased risk of dying from the common adult epithelial cancers, such as lung cancer, is unknown. This study evaluated mortality, from 1925 through 1997, for 1,604 1-year survivors of retinoblastoma diagnosed in 1914-1984. Mortality was calculated from the appropriate U.S. death rates. Risk of death from other cancers was higher for 964 hereditary retinoblastoma patients (standard mortality ratio [SMR] = 47.0) than for 640 nonhereditary patients (SMR = 3.8). Five lung cancer deaths occurred among the hereditary patients compared with 0.33 expected (SMR = 15.2). Lung cancer was diagnosed by age 40 in the three patients who smoked most heavily. Smoking rates were not abnormally high in retinoblastoma survivors; this excess of early-onset lung cancers suggests that carriers of RB1 mutations may be highly susceptible to smoking-induced lung cancers. No lung cancer deaths occurred among the nonhereditary patients. Hereditary retinoblastoma patients should be specially targeted for smoking cessation. (Kleinerman RA, Tarone RE, Abramson DH, Seddon JM, Li FP, Tucker MA. Hereditary retinoblastoma and risk of lung cancer. J Natl Cancer Inst 2000;92:2037-2039) New System to Characterize Single-nucleotide Polymorphisms A system for the rapid identification, assay development, and characterization of gene-based single-nucleotide polymorphisms (SNPs) was reported. This system identifies candidate SNPs from public "expressed sequence tag" resources and automatically designs assay reagents for detection by a chip-based, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. This system was validated by a genomewide collection of reagents for 9,115 gene-based SNP genetic markers. (Buetow KH, Edmonson M, MacDonald R, Clifford R, Yip P, Kelley J, Little DP, Strausberg R, Koester H, Cantor CR, Braun A. High throughput development and characterization of a genomewide collection of gene-based single nucleotide polymorphism markers by chip-based matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Proc Natl Acad Sci 2001;98:581-584) p53 Mutations and Early-onset Cancers This study examined cancer occurrences among a series of 45 families,
plus 140 other affected cases and kindreds reported in the literature,
to clarify the tumor spectrum associated with inherited p53 mutations.
The analyses included all cancers in patients with a germline p53 mutation
and in first-degree relatives, who were almost 50 percent more likely
to be carriers. Among 738 evaluable cancers, 569 (77 percent) were the
six tumor types (breast and adrenocortical carcinomas, sarcomas of the
bone and soft tissues, brain tumors, and leukemias) associated with
Li-Fraumeni syndrome. The remaining 169 (23 percent) cancers included
diverse carcinomas of the lung and gastrointestinal tract, lymphomas,
and other neoplasms that occurred at much earlier ages than expected
in the general population. Unusually early ages at diagnosis are characteristic
of hereditary cancers and suggest that carriers of germline p53 mutations
confer increased risk for a wide range of neoplasms. (Nichols
KE, Malkin D, Garber JE, Fraumeni JF, Li FP. Germ-line p53 mutations
predispose to a wide spectrum of early-onset cancers. Cancer Epidemiol
Biomarkers Prev 2001;10:83-87) Kidney Cancer Relationship of Obesity and Hypertension to Kidney Cancer A nested case-control study of physical examination data for 759 men
with renal cell cancer and 136 men with renal pelvis cancer was conducted
among a cohort of Swedish men. The physical examination data studied
were taken prior to the ones leading to a cancer diagnosis. Compared
with men in the lowest range for body mass index, men in the middle
range had a 30 to 60 percent greater risk of renal cell cancer, and
men in the highest range had nearly double the risk. Blood pressure
and renal cell cancer risk were directly associated, even after data
from the first five years of follow-up were excluded to reduce possible
effects of preclinical disease. At the sixth year of follow-up, the
risk rose or fell with the change in blood pressure, after data were
adjusted for baseline measurements. Current or former smokers had a
greater risk than nonsmokers of both renal cell cancer and renal pelvis
cancer. No relationship was found between body mass index or blood pressure
and the risk of renal pelvis cancer. (Chow WH, Gridley
G, Fraumeni JF, Jarvholm B. Obesity, hypertension, and the risk of kidney
cancer in men. N Engl J Med 2000;343:1305-1311) Multiple Myeloma Diet and Nutrition as Risk Factors for Multiple Myeloma Data from a food frequency questionnaire were analyzed for 346 white
and 193 black multiple myeloma patients and for 1,086 white and 903
black controls. Reduced risks were related to frequent intake of cruciferous
vegetables (odds ratio [OR] = 0.7, 95 percent CI = 0.6-0.99) and fish
(OR = 0.7, 95 percent CI = 0.5-0.9) in both races combined, and to vitamin
C supplements in whites (OR = 0.6, 95 percent CI = 0.5-0.9) and in blacks
(OR = 0.8, 95 percent CI = 0.5-1.4). The frequency of vitamin supplement
use was greater among white controls than black controls. Elevated risks
were associated with obese versus normal weight (OR = 1.9, 95 percent
CI = 1.2-3.1 for whites and OR = 1.5, 95 percent CI = 0.9-2.4 for blacks),
and the frequency of obesity was greater among black controls than among
white controls. The greater use of vitamin C supplements by whites and
the higher frequency of obesity among blacks may explain part of the
high incidence of multiple myeloma among blacks, compared with whites,
in the United States. (Brown LM, Gridley G, Pottern
LM, Baris D, Swanson CA, Silverman DT, Hayes RB, Greenberg RS, Swanson
GM, Schoenberg JB, Schwartz AG, Fraumeni JF. Diet and nutrition as risk
factors for multiple myeloma among blacks and whites in the United States.
Cancer Causes Control 2001;12:117-125)
Nutrition Anorexia Nervosa and Cancer Risk Patients with anorexia nervosa (2,151 women and 186 men) from 1970 through 1993 were identified in the population-based Danish Psychiatric Case Register and the National Registry of Patients and linked to the Danish Cancer Registry to determine whether energy restriction reduces the incidence of malignant tumors. Compared with the general population, the overall cancer incidence among women with anorexia nervosa was reduced by a factor of 0.80 (95 percent CI = 0.52-1.18) on the basis of 25 observed and 31.4 expected cases. Among men, 2 cases of cancer were observed, both in the brain, but 0.2 cases were expected. (Mellemkjaer L, Emborg C, Gridley G, Munk-Jorgensen P, Johansen C, Tjonneland A, Kjaer SK, Olsen JH. Anorexia nervosa and cancer risk. Cancer Causes Control 2001;12:173-177) Obesity and Cancer Risk In a population-based cohort of 28,129 hospital patients with any
discharge diagnosis of obesity from 1965 through 1993, cancer incidence
was monitored by record linkage to the nationwide Swedish Cancer Registry.
Overall, a 33 percent excess incidence of cancer was seen in obese persons
(25 percent in men and 37 percent in women). Significant risk elevations
were observed for cancers of the small intestine (standard incidence
ratio [SIR] = 2.8; 95 percent CI = 1.6-4.5), colon (SIR = 1.3; 95 percent
CI = 1.1-1.5), gallbladder (SIR = 1.6; 95 percent CI = 1.1-2.3), pancreas
(SIR = 1.5; 95 percent CI = 1.1-1.9), larynx (SIR = 2.1; 95 percent
CI = 1.1-3.5), renal parenchyma (SIR = 2.3; 95 percent CI = 1.8-2.8),
bladder (SIR = 1.2; 95 percent CI = 1.0-1.6), cervix uteri (SIR = 1.4;
95 percent CI = 1.1-1.9), endometrium (SIR = 2.9; 95 percent CI = 2.5-3.4),
ovary (SIR = 1.2; 95 percent CI = 1.1-1.5), brain (SIR = 1.5; 95 percent
CI = 1.2-1.9), and connective tissue (SIR = 1.9; 95 percent CI = 1.1-3.0),
as well as for lymphomas (SIR = 1.4; 95 percent CI = 1.0-1.7). Higher
risk was observed for Hodgkin's disease only in men (SIR = 3.3; 95 percent
CI = 1.4-6.5) and for non-Hodgkin's lymphoma only in women (SIR = 1.6;
95 percent CI = 1.2-2.1). The association of obesity with risk of breast,
prostate, and pancreas cancers was modified by age. (Wolk
A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adami
HO. A prospective study of obesity and cancer risk (Sweden). Cancer
Causes Control 2001;12:13-21) Ovarian Cancer Certain Ovarian Cysts Are Not Ovarian Cancer Precursors Transvaginal ultrasonographic findings from the examinations of 20,000
postmenopausal women were compared with data on the established risk
factors for ovarian cancer obtained from self-administered questionnaires.
High parity, a strong ovarian cancer protective factor, was negatively
associated with complex cysts (odds ratio for at least five births versus
no births = 0.72). Neither long-term oral contraceptive use, another
strong protective factor, nor family history of ovarian cancer or multiple
breast cancers, both strong risk factors, was associated with complex
cysts. Other identified abnormalities, including simple cysts, bilateral
cysts, or all abnormalities combined, also did not share established
risk factors for ovarian malignancy. A very small proportion of clinically
silent ovarian abnormalities found on ultrasonography are determined
to be ovarian cancers; the remaining complex cysts and other clinically
suspicious abnormalities do not appear to be immediate precursors of
ovarian cancer. (Hartge P, Hayes R, Reding D, Sherman
ME, Prorok P, Schiffman M, Buys S. Complex ovarian cysts in postmenopausal
women are not associated with ovarian cancer risk factors: preliminary
data from the prostate, lung, colon, and ovarian cancer screening trial.
Am J Obstet Gynecol 2000;183:1232-1237) Prostate Cancer Body Size and Prostate Cancer: A Population-based Case-control Study in China A population-based case-control study was conducted in Shanghai to
investigate whether body size plays a role in prostate cancer etiology
and to explain the rapid increase in the prostate cancer incidence rate
in China. On the basis of 238 newly diagnosed cases and 471 controls,
a high waist-to-hip ratio, an indicator of abdominal adiposity, was
related to excess risk, and men in the highest quartile had an almost
threefold risk (odds ratio = 2.71; p for trend = 0.0001) compared
with men in the lowest quartile. In contrast, men in the highest quartile
of hip circumference had a reduced risk (odds ratio = 0.46; p
for trend = 0.0002) relative to men in the lowest quartile. No association
was found for height, usual adult weight, or preadult and usual adult
body mass index. These results suggest that even in a very lean population
(average body mass index = 21.9 mg/k2), abdominal adiposity may be associated
with an increased risk of clinical prostate cancer, pointing to a role
of hormones in prostate cancer etiology. (Hsing AW,
Deng J, Sesterhenn IA, Mostofi FK, Stanczyk FZ, Benichou J, Xie T, Gao
YT. Body size and prostate cancer: a population-based case-control study
in China. Cancer Epidemiol Biomarkers Prev 2000;9:1335-1341)
Radiation Bone and Liver Cancer in Mayak Plutonium Plant Workers Bone and liver cancer mortality were evaluated among 11,000 "Russian
Mayak" Production Association workers who were exposed to internally
deposited plutonium and external gamma radiation. After data were adjusted
for cumulative external radiation dose, relative risks (RR) of 17.0
for liver cancer and of 7.9 for bone cancer were observed among workers
with plutonium body burdens estimated to exceed 7.4 kBq, and RRs of
2.8 for liver cancer and 4.1 for bone cancer were found among workers
in the plutonium plant who were not routinely monitored for plutonium
on the basis of urine measurements. In addition, analyses that treated
the estimated plutonium body burden as a continuous variable indicated
increasing risk of each cancer with increasing burden (p < 0.001).
RRs tended to be higher for females than for males, probably because
of the lower baseline risk and the higher levels of plutonium measured
in females. (Koshurnikova NA, Gilbert ES, Sokolnikov
M, Khokhryakov VF, Miller S, Preston DL, Romanov SA, Shilnikova NS,
Suslova KG, Vostrotin VV. Bone cancers in Mayak workers. Radiat Res
2000;154:237-245 and Gilbert ES, Koshurnikova NA, Sokolnikov M, Khokhryakov
VF, Miller S, Preston DL, Romanov SA, Shilnikova NS, Suslova KG, Vostrotin
VV. Liver cancers in Mayak workers. Radiat Res 2000;154:246-252)
Statistics Analyzing Exposure-time-response Relationships with a Spline Weight Function A procedure was designed to estimate a weight function within a generalized
linear model, and ultimately to examine the time-dependent effects of
exposure histories on disease. The shape of the weight function, which
is modeled as a cubic B-spline, gives information about the impact of
exposure increments on disease risk at different times. The method was
evaluated in a simulation study and applied to data on smoking histories
and lung cancer from a recent case-control study in Germany. (Hauptmann
M, Wellmann J, Lubin JH, Rosenberg PS, Kreienbrock L. Analysis of exposure-time-response
relationships using a spline weight function. Biometrics 2000;56:1105-1108)
Viruses Transmission of HIV-1 by Pregnant Women In a collaboration among seven European and U.S. prospective studies,
44 cases of vertical HIV-1 transmission were identified among 1,202
pregnant women with RNA virus loads of less than 1,000 copies/mL at
delivery or at the measurement closest to delivery. For mothers receiving
antiretroviral treatment during pregnancy or at the time of delivery
(or both), the transmission rate was 1.0 percent (8 of 834), compared
with 9.8 percent (36 of 368) for untreated mothers. In multivariate
analysis adjusting for study, transmission was significantly lower with
antiretroviral treatment (odds ratio [OR] = 0.10), cesarean section
(OR = 0.30), greater birth weight (OR = 0.92), and higher CD4 cell count
(OR = 0.86). (Ioannidis JPA, Abrams EJ, Ammann A, Bulterys
M, Goedert JJ, Gray L, Korber BT, Mayaux MJ, Mofenson LM, Newell ML,
Shapiro DE, Teglas JP, Wilfert CM. Perinatal transmission of human immunodeficiency
virus type 1 by pregnant women with RNA virus loads < 1000 copies/mL.
J Infect Dis 2001;183:539-545) |
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DCEG PEOPLE IN THE NEWS |
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Dr. Erin Bell, a fellow in the Occupational Epidemiology Branch, received the Sidney Kark Distinguished Teaching Assistant Award from the University of North Carolina's School of Public Health, Epidemiology Department. Dr. Mitchell Gail, Chief of the Biostatistics Branch, delivered three invited talks in the last few months. In September, he delivered the Presidential Invited Address to the International Society for Clinical Biostatistics in Trento, Italy, on the topic, "A comparison of cohort, case-control, and family-based designs." In November, he addressed the Second Seattle Symposium in Biostatistics. In January, he spoke at the Inaugural Meeting of the East Mediterranean Region of the International Biometric Society, where he compared designs for estimating gene penetrance.
In September, Dr. Mary Lou McMaster, of the Genetic Epidemiology
Branch, was an invited speaker and participant at a workshop on Waldenström's
macroglobulinemia, sponsored by Dr. Bruce Cheson of the NCI Cancer Therapy
Evaluation Program. The workshop convened preeminent researchers in
this area to reach a consensus about disease definition and to establish
international research priorities and criteria. Dr. McMaster's presentation
was entitled "Family studies in Waldenström's macroglobulinemia." |
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COMINGS . . . GOINGS |
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Dr. Catherine Metayer, formerly of the Radiation Epidemiology Branch, has relocated to Northern California.
The Division of Cancer Epidemiology and Genetics had the pleasure of working with Dr. Ruggero Montesano, who joined the Viral Epidemiology Branch (VEB) as a visiting scientist in December. Dr. Montesano is a molecular pathologist whose main interests are in environmental carcinogenesis and molecular epidemiology. He presently focuses on esophageal and liver cancers. From 1980 through 1999, he was Chief of the Unit of Mechanisms of Carcinogenesis at the International Agency for Research on Cancer (IARC) in Lyon, France. During his three months at DCEG, Dr. Montesano split his time between VEB and the Laboratory of Human Carcinogenesis in the Division of Basic Sciences. In collaboration with Dr. Greg Kirk of VEB, Dr. Montesano will continue to work on analyses of the Gambia Liver Cancer Study and on detection of molecular markers of liver cancer in serum and plasma. Dr. Montesano returned to IARC at the end of February. Dr. Barbara Mulach, an NIH Presidential Management Intern, worked with Ms. Betsy Duane in DCEG through February. Prior to coming to NIH, Dr. Mulach received her Ph.D. in biochemistry from the University of Alabama at Birmingham. Since she began the internship program in 1999, she worked in several offices at NIH, including NIAID's Office of Policy Analysis; NLM's Office of Communications and Public Liaison; and NCCAM's Office of Communications, Science Policy and Public Liaison. As an intern, she also spent four months at the National Science Foundation, working with the Division of Graduate Education. At DCEG, Dr. Mulach participated in communications-related activities and projects. Dr. Stephanie Weinstein, a fellow in the Nutritional Epidemiology Branch, has accepted a position at the Center for Nutrition Policy and Promotion, U.S. Department of Agriculture, in Washington, D.C. |
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MOLECULAR EPIDEMIOLOGY LEARNING SERIES |
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WORKSHOP ON NEUROFIBROMATOSIS 2 (NF2) | ||||||
The workshop began with a series of presentations outlining the current
status of NF2 research and management as well as a description of research
goals in various areas, including genetics, imaging, electronic implants,
cell biology, mouse models, and new therapies. Participants then divided
into five groups to discuss assigned themes: auditory brainstem and
cochlear implants, quality of life issues, nonsurgical treatment of
VS, surgical management of NF2, and genetics. Rapporteurs presented
each group's conclusions and priorities for future research to all workshop
attendees. Workshop leaders plan to publish the proceedings and to use
the research and management priorities developed at the meeting to create
an integrated system for managing NF2 patients and for coordinating
research efforts. |
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CHORNOBYL RESEARCH PROGRAM MEETINGS | ||||||
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