mout,h and pharynx" (48). Since most. people who drink large amounts of alchohol regularly are also heavy users of tobacco, it is difficult to identify the relative contribution of these two factors or t'he role of Ihe nutritional problems often associated with heavy alcohol use. ,4dditional data have, been reported by Moore (&?), on patients developing second primnrv mouth and throat cancers, after having heen cured for at. least thrie years prior to development. of the cancer. These patients were all asymptomatic for at least three years prior to development of the second cancer. Of 117 patients with adequate, smoking histories only 4 of Ji-1 (0 ljercent) who quit smoking after the first, cancer, developed a new ljritnary. On the other hand, 27 of 74 patients (36 percent) who continued to smoke del-eloped a second primary cancer. These data supl)ort the important contribution of smoking to the etiology of mouth and throat cancer. Roth, et al. (73. 74) recently have shown that the dTe-binding capacit,y of DSA of oral epithelial cells is significantly enhanced in cigarette smokers in contrast to nonsmokers, probably reflecting an increase in the DSA content of oral epithelial cells in smokers. This suggests some alteration in the Ds.1 which ma\- be a factor in oral carcinogenesis. Smokers had \-alues of dye-binding capacity inter- mediate between nonsmokers and 21 patients with proven oral cancer. Those smokers who refrained from smoking for up to nine months showed a significant. decrease towards more normal I-alues. It is clear that people who use tobacco hare higher rates of oral cancer than those who do not. Research is needed to identify the dose relationships, to determine whether or not there are dosage thresholds, and to clarify the relationships between dosage, style of tobacco use, and part of the mouth affected. It seems likely that factors such as alcohol consumption, nutritional problems, and oral hygiene mas be interrelated with the tobacco habit in a fairly complex pattern. More resenrrh is needed to clarify these relationships. For patients with oral cancer, and probably for those at a high risk of oral cancer because of other exposures, cessation of tobacco use can make an important contribution to reducing the, risk of a new primary cancer. CA?;CER OF THE LARYNX Cancer of the larynx is mainly a disease of male smokers. Of t,he 2,629 deaths in 1965, over 88 percent, were men. The 1067 report noted that the death rate for cancer of the larynx had not, increased signifi- cantly since 1950. The incidence rates, however, have shown a steady increase since 19% 101 FIWRE &.Ige-adjusted rates of the incidence of cancer of the larynx, for males and females : Connecticut, 193&1962 SOURCE : Eisenberg et al. (24). The American Pancer Society (2) estimates the occ.urence of 6,000 new cases of cancer of t.he larynx in 1968 but only about, 2,800 deaths, due to relative curability of t,his disease if diagnosed early. Several retrospective studies have again shown the extremely high rate of smokers [ 98 percent (86)) 92 percent (75) ] among paCents with cancer of the larynx. CAKCER OF THE ESOPHAGUS As reported in the 1967 Report (92) the death rates for cancer of the esophagus have increased only slightly in the period 1950-1964. The large scale prospective studies (18, 19> 34, 4s) showed mortality ra.tios up to 11 in heavy cigarette smokers, while pipe and/or cigar smokers had ratios up to 5. Preliminary data from a prospective study (37) in Japan also indi- cate an increased frequency of death from cancer of the esophagus among smokers as compared to nonsmokers. No further information has become available on the relationship of esophageal cancer to alcohol and/or other confounding variables as discussed in the 1967 report. 102 CANCER OF THE PANCREAS The 196'i report implied a rellat,ionship between smoking and pan- creatic cance,r due to the somewhat higher mortalit,y ratios observed in three of the. large scale prospective epidemiologic studies. The ,Imerican Cancer Society estimates that. deaths due to cancer of the pancreas will total 15,000 in 1968 with a male/fe.male ratio of approvimate.ly :< : 2. The overall death rate for cancer of the pancreas has shown a steady rise; from 7.2 to 8.4 in males ( + 17 percent.) and et.4 to 4.9 ( fll percent) in females, for the time period 1953~55 to 196-65 (a). The incidence rates have increased almost 50 percent in males since 1935, with no apparent increase for fernala. In the past. year? preliminary evidence from two retrtrqwtive studies (&3,102?) has showi that only 10 percent of the patients with cancer of the pancreas are nonsmokers. The risk of developing cancer of the pan- creas appears to increase in proport ion to the amount smoked. Preliminary data from a prospective study (37) in Japan also shops a significantly higher frequency of deaths from pancreatic cancer among smokers a.s compared to nonsmokers. PANCREAS - Male --- Female FIGURE -l--Age-adjusted rates of the incidence of cancer of the pancreas, for males and females : Connecticut, 19X*1962. SOURCE: JGisenberg, et al. (24). ?J5-Ii31 0-68-S 103 These st.ndies st,rengthen the earlier indications of an ass&&on be- t\wen smoking and pancreatic cancer, but. further research is needed in this are.a to elucidate the significance of this association. GENITO-URINARY CANCER CANCER OF THE BLADDER As stated in the 1967 Report, there has been no increase in male or female death rates for cancer of the bladder over the 15 year period 1950-1964. However, t.he incidence rates for males have increased orer 75 pe.rcent in the 25-year period from 1935-37 to 1960-62, and about 26 percent. in the 15 year period from 19454i to 1960-62. Deeleg, et al. (16) reported on a retrospective study of 127 patients with cancer of the bladder and 126 patients wi-it.h lung cancer, all matc.hed with controls. The smoking "factors" (amount times duration of smoking) were significantly greater among cases than controls for both cancer sites. Even by age-groups, the "mean smoking factor" for either cancer n-as higher for cases than for controls. Preliminary data FICLTLE Z-Age-adjusted rates of the incidence of cancer of the bladder, for males and frmalw : (`onwcticut, l%~l!W2. SOURCE: Eisenberg, et al. (24) 104 from a prospective study (37) in ,Japan shows a higher frequency of deaths from bladder cancer among smokers. Certain amino acids, as found in tobacco, form trace amounts of alpha- and be&naphthylamines upon pyrolysis (59). The latt.er agent is an estab1ishe.d bladder carcinogen. So far, howewr, only it.s isomeric alpha-naphthylamines `has been identified in cigarette smoke (GO. 67). Further investigat,ion is ne.eded on the carcinogenic metabolites of tryptophan which have been shown to be inere.ased in the urine of cigarette smokers (9%`). CANCER OF THE KIDNEY The 1967 Report did not, mention the association between smoking and cancer of the kidney. The U.S. Veterans study (4~) shops increasing mortality ratios for cancer of the kidney with the amount of cigarette smoking. There is no apparent relationship with pipe and/or cigar smoking. TABLE 3.-Mortality ratios and death rates for cancer of the kidney in U.S. ,ueterans, by age, type and amount smoked for current smokers only 1 , Number of cigarettes smoked per day Pipe and/or Cigars 0 1-9 l&20 21-39 40 and Pipe cigars over __- -1 Mortality ratios- _--_ 1. 00 97 1. 34 1. 68 2. 75 1. 15 77 1. 32 Death rates: Age45-54_.._-_.__.._____.___..~..- _._--_ ---__- ~.._~..___._._____ Age 55-64._----_ 8 5 Age 65-74__mm--_ 14 7 Age 75-W---- 7 -_-._--_---- --_--_ ---__- Somce: Kahn, IX. A. (46). TABLE 4.-Mortality ratios and death rates for cancer of the kidney in male cigarette smokers, by speci$ed age groups Cigarette smokers - Age 4564 Age 65-79 - Mortality ratios_--~.--~.~---~---~~--------~----~--- 1. 42 Deathrates---_--- _.___._. --_---~_--_~---~.---.-___; ' (416 , 1. 57 1 (15)23 1 Numbers in parentheses indicate death rates for persons who have never smoked regularly SOURCE: Hammond, E. C. 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