ON THE POSITIVE SID E A POSITION PAPE R G .8_ GORI JANUARY In7 1 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 INTRODUCTIO N During the last decade and especially in the last few years scientific evidence has been gradually emerging, and now indicates that smoking may in fact provide a net contribution in the prevention of certain diseases and in extending life expectancy . * Prevention of diseases that are estrogen-dependent, especially breast and endometrial cancer, on account of the reduced production of endogenous estrogen in smokers . * Prevention of diseases that are linked to secretory and muscular kinetics of the lower intestines, such as colon cancer and ulcerative colitis, on account of the effect of smoking on the motility and mucous secretion of the colon . * Prevention of neurological diseases such as Parkinson's, where nicotine appears to play a role at the level of neuron receptors in the central nervous system . * Prevention of hypertension and obesity in smokers, probably due to a multiplicity of effects of nicotine and other smoke components on central appetite regulators, digestive efficiency, and vascular relaxation . Hypertension and obesity are recognized as being closely linked, and as being significant risk factors in cardiovascular disorders . 2 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 • Prevention of other diseases such as sarcoidiosis, by mechanisms as yet undetermined . This, and the growing realization that many of the diseases that 1( are allegedly linked to smoking are in fac t,l ked to a variety of other risk factors (for instance asbestos and radon for lung cancer ; cholesterol, high blood pressure and lack of exercise for cardiovascular diseases) inevitably lead to a reduction of the alleged epidemiologic impact of smoking . Additional scientific evidence shows that statistics on the alleged association of lung cancer and cardiovascular diseases with smoking have been collected without corrections for significant confounders, and therefore need also to be reconsidered from a basic methodological point of view ; this would also lead to a reduction of the alleged impact o f smoking . All the evidence here noted is the result of independent studie s not funded by tobacco interests . This suggests that etter nd more ~ .. lav extensive evidence night be actually available, since the existin g reports were produced in a climate strongly prejudicial to smoking . Thus, using the very same criteria and methods that enti-smoking advocates have represented as credible for so many years, it is becoming apparent that the net sum of longevity effects of smoking may actually turn out positive . Lon D~. S {~R i tlni li.,.►Q~`"~ 3 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 Estrogen-dependent Disease s Several studies show that smoking has a preventive effect of abou t (20-30% for breast cancer and up to 50~ for endometrial cancer . Both o f ~these"cancers are stimulated by internally produced estrogen ; scientific evidence indicates that smoking depresses the production of endogenous estrogens, favoring among other things the onset of menopause (on th e average 1 .5 years earlier) . c 1 .1 There is also some evidence that oral contraceptives may be risk factors for such cancers, although the correlation is tenuous, probably because oral contraceptives are not pure estrogen, but a mixture of estrogen, progesterone and other antagonistic hormones . Some earlier studies have found no protective effect of smoking on breast cancer, but newly published evidence shows that such an effect is more evident only for specific types of breast cancers, namely those poor in estrogen receptors . Thus any future investigation needs to discriminate for estrogen receptor-poor cancers, where the preventive effect of smoking is likely to be more pronounced . It is desirable to encourage epidemiologic and mechanistic studies in this area . Colon Disorder s There is evidence that smoking affects both the mucous secretion and the motility of the colon . Such effects are probably responsible for the prevention of colon cancer (up to 50%) and ulcerative colitis (over 75%) in smokers . It is necessary to further study the mechanism s 4 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 of action of smoking on the colon, and to encourage further epidemiologic surveys, in order to increase the published literature about the observed protective effects . Neurological Disorder s Parkinson's disease, a neurological illness, is very rare among smokers, probably on account of the stimulatory effects of nicotine on central nervous system receptors . Further studies at the receptor level may be desirable, but epidemiologically this protective effect of smoking is universally recognized . The pathological features of Parkinson's' disease have much in common with other diseases such as Alzheimer's, and it is desirable to promote epidemiologic as well as mechanistic studies to uncover the effects of smoking on related diseases . Parkinson's disease cause s around 5,000 deaths a year If smokers were to quit, an additional G L 1,000-2,000 deaths a year could be expected . Cardiovascular Disease s There is uncontrovertible evidence that smokers have significantly lower blood pressure levels than nonsmokers . High blood pressure is a recognized risk factor for cardiovascular diseases . Several larg e intervention trials, involving several thousand individuals, have forced changes in lifestyle habits such as smoking and diet, with the aim of preventing cardiovascular diseases . Of these studies the bes t 5 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 known are the MRFIT or Framingham Study conducted by the National Heart and Lung Institute in the United States, and the Gotheborg Study in Sweden . Both studies have failed to show that a reduction in smoking habits results in lesser cardiovascular diseases, thus indicating lack of a causal linkage . In fact, the MRFIT trial in the United States showed that the participants in the intervention trials had actually slightly greater mortality rates than controls . The epidemiologic evidence in cardiovascular diseases is definitely a multifactorial one, and is clearly subject to gross confounding factors . Prominent epidemiologists have repeatedly pointed out that the alleged causal relationship of smoking and cardiovascular diseases is based on the most circumstantial of evidence, and even the argument of a 25% risk contribution can not be factually sustained . C It is desirable to encourage surveys that would reinforce the findings of low blood pressure in smokers, and studies that may elucidate the mechanisms involved . At the same time it is necessary to encourage a critical review of the epidemiologic and statistical standards of evidence that have been used to link cardiovascular diseases and smoking . The main bias is due to the great prevalence of cardiovascular diseases which affect over 50% of the population ✓ regardless of smoking . Under such conditions it has been demonstrated and it is intuitive - that all sorts of spurious statistical and epidemiological relations can be construed . r) Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 Obesity Scientific evidence shows that smoking helps control weight . People who do not smoke or who have quit smoking are on the average som e ttit's . 20% overweight compared to smokers . If the approximately 50 millio n Americans who smoke should quit smoking, statistics show that th e acquired 20% overweight would cause an estimated 50,000 premature deaths a year . Such effects of obesity have been recognized for decades as a universal foundation of actuarial life tables used by underwriters c„k tiv%-~ throughout the world . It is desirable to encourage epidemiological and mechanistic studies on smoking and weight control . Lung Cance r Of the 110,000 new cancer causes a year in the United States, it has been universally accepted that at least 10,000 cases occur in nonsmokers . Asbestosis, a major recognized risk factor for lung cancer, is now identified as the probable cause for 10,000-20,000 lung cancer cases a year . Currently emerging evidence indicates that from 15,000-25,000 cancers per year are probably linked to radon exposure in contaminated homes . Other occupational exposures have been linked to probably another 10,000-20,000 cases a year . This new balance of risk factors in lung cancer causation reduces from 100,000 to perhaps between 35,000-65,000 a year the number of cancer cases allegedly attributed to smoking . 7 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 Moreover, recent pathological evidence demonstrates that smokers are more likely to be diagnosed as having lung cancer, while the disease often goes undiagnosed in nonsmokers . The correction for this diagnostic bias would obviously increase the total number of lung cancers diagnosed, but would also decrease the proportion that is wrongly attributed to cigarette smoking . In other terms, lung cancer is a frequent disease regardless of smoking, and anti-smoking advocates should be made to recognize that only a small fraction of lung cancers could be linked to smoking by their allegations . Other Disease s Sarcoidiosis accounts for a very small portion of annual mortality . If smokers were to quit, perhaps an additional 1,000 deaths a year may occur . 8 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 N ~. 1 >jJD ~ C O OL O 7 d O Ln N O .--~ L1) 1 1 1 4 .1 ~- G E LI) c I O Il) N CO CO M . Lf) .-+ 0 1 4-, O N Ln I1 Lo U In 4) L (') N 1 0 N L (D Ll) - LC) Ln - O 1 0 1. 1 LO C.) L .) 0 a-1 >'v +J a/ C C 7 •r 4J .0 . i •r O L L E U CD O r-1 aC) M N - O O O Lf) O N U) O L1) L1) O L') C%j N 1 1 +J In C G +J •0 r- O _ i1, N L L O O G L!) O O O O C O~ M) N O O O N M O - .-r L') C A C C) 1 Y O c~ c c V) Ln r C.; V. G a..1 v1 O J C) L O 0 V L +-) N ti L Co 4) 0 0 'o C W U Ln 'J L O +.1 D +~ L v U> ' . N C.r 4) L. .O -0 U O o C 0 O •r C U - L Y 'C (u L L/) C LO 41 . C) Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 GENETICS AND VARIA E 1 . Cederlof, R ., L . Friberg, Z . Hrubec and U . Lorich . The relationship of smoking and some social covariables to mortality and cancer morbidity, The Department of Environmental Hygiene, The Karolinska Institute, Stockholm, Sweden, 1975 . 2 . Douglas, J .G ., W .G . Middleton, J . Gaddie, G .R . Petrie, Y .F .J . Choo-Kang, R .J . Prescott and G .K . Crompton . Sarcoidosis : a disorder commoner in non-smokers? Thorax, 41 :787-791, 1986 . 3 . Feinstein, A .R . The bias caused by high values of incidence for p1 in the odds ratio assumption that 1 - pl = 1, J . Chron Dis ., 39 :485-487, 1986 . 4 . Godwin-Austen, R .B ., P .N . Lee, M .G . Marmot and G .M . Stern . Smoking and Parkinson's disease, J . of Neurology, Neurosurgery, and Psychiatry, 45 :577-581, 1982 . 5 . Idle, J .R . and J .C . Ritchie . Probing genetically variable carcinogen metabolism using drugs, In : Human Carcinogenesis, Academic Press, New York, 1983 . 6 . Knudson, A .G . Genetics of human cancer, J . of Cellular Physiology Supplement 4 :7-11, 1986 . 7 . Leu, R .E . and T . Schaub . Does smoking increase medical care expenditure? Soc . Sci . Med ., 17 :1907-1914, 1983 . 8. Liang, K .Y ., T .H . Beaty and B .H . Cohen . Application of odds ratio regression models for assessing familial aggregation from case-control studies, American Journal of Epidemiology, 124 :678-692, 1986 . 9 . Schneider, N .R ., W .R . Williams and R .S .K . Chaganti . GenoLic epidemiology of familial aggregation of cancer, In : Advances in Cancer Research, Vol . 47, Academic Press, New York, 1986 . 10 . Snyder, S .H . and R .J . D'Amato . Predicting Parkinson's disease, Nature, 317 :198-199, 1985 . 11 . Wiles, P .G ., J . Wentworth, R .G . Jones, A .J . Birtwell, A . King, M .H . Stickland, P .J . Grant, D .E . Price and J .K . Wales_ Is smoking really a risk factor for diabetic retinopathy? Diabetic Medicine, 3 :577A, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 12 . Williams, R .R . and J .W . Horn . Association of cancer sites with tobacco and alcohol consumption and socioeconomic status of patients : Interview study from the Third National Cancer Survey, J . Nat'l . Cancer Inst . 58 :525-547, 1977 . 13 . Wright, V .B . Will quitting smoking help Medicare solve its financial problems? Inquiry, 23 :76-82, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 COLON 1 . Amery, K .V . Smoking and ulcerative colitis, British Medical Journal 288 :1307, 1984 . 2 . Cope, G .F ., R .Y . Heatley and J . Kelleher . Smoking and colonic mucus in ulcerative colitis . British Medical Journal 293 :481, 1986 . 3 . De Castella, H . Non-smoking : a feature of ulcerative colitis, British Medical Journal 284 :1706, 1982 . 4 . Enstrom, J .E . and F .H . Godley . Cancer mortality among a representative sample of nonsmokers in the United States during 1966-68, J . Nat'l . Cancer Inst . 65 :1175-1183, 1980 . 5 . Entrican, J .N . Chronic inflammatory bowel disease, cigarette smoking, and use of oral contraceptives . British Medical Journal 292 :1464, 1986 . 6 . Garfinkel, L . Cancer mortality in nonsmokers : prospective study by the American Cancer Society, J . Nat'l . Cancer Inst . 65 :1169-1173, 1980 . 7 . Hammond, E .C . Smoking in relation to the death rates of one million men and women, National Cancer Institute Monograph No . 19, pp . 127-204, 1984 . 8 . Harries, A .D ., A . Baird and J . Rhodes . Non-smoking : a feature of ulcerative colitis, British Medical Journal, 284 :706, 1982 . 9 . Holdstock, G ., D . Savage, M . Harman and R . Wright . Should patients with inflammatory bowel disease smoke? British Medical Journal 288 :362-, 1984 . 10 . Kennedy, H .G . Smoking and ulcerative colitis, British Medical Journal 288 :1307, 1984 . 11 . Logan, R . and M .J .S . Langman . Smokino and ulcerative colitis, British Medical Journal 288 :1307, 1984 . 12. Roberts, C .J . and R . Diggle . Non-smoking : a feature of ulcerative colitis, British Medical Journal 285 :440, 1982 . 13 . Thornton, J .R ., P .M . Emmett and K .W . Heaton . Diet and ulcerative colitis, British Medical Journal, 280 :293-294, 1980 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 14 . Thornton, J .R ., P .M . Emmett and K .W . Heaton . Smoking, sugar, and inflammatory bowel disease, British Medical Journal 290 :1786-1787, 1985 . 15 . Williams, R .R ., P .O . Sortie, M . Feinleib, P .M . McNamara, W .B . Kannel and T .R . Dawber . Cancer incidence by levels of cholesterol, JAMA 245 :247-252, 1981 . 0 CA CO 0 Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 NICOTIN E 1 . Gurkalo, V .K . and N .I . Volfson . Nicotine influence upon the development of experimental stomach tumors, Arch . Geschwulstforsch . 52 :259-265, 1981 . 2 . Habs, M . and D . Schmahl . Influence of nicotine on N-liitrosomethylurea-induced tumors in rats, Klinische Wochenschrift 62(Suppl . II) :105-108, 1984 . 3 . Ito, N ., S . Fulushima, T . Shirai, A . Hagiwara and K . Imaida . Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis, pp . 399-407 . 4 . Rogers, D .F ., D .A . Williams and P .K . Jeffery . Nicotine does not cause 'bronchitis' in the rat, Clinical Science 70 :427-433, 1986 . 5 . Toth, B . Effects of long term administration of nicotine hydrochloride and nicotinic acid in mice, Anticancer Research 2 :71-74, 1982 . 6 . Warburton, D .M ., K . Wesnes, K . Shergold and M. James . Facilitation of learning and state dependency with nicotine, Psychopharmacology 89:55-59, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 CVD 1 . Coates, T .J . and Y .C . Li . Does smoking cessation lead to weight gain? The experience of asbestos-exposed shipyard workers, Amer . J . of Public Health 73 :1303-1304, 1983 . 2 . Friedewald, W .T . and T .J_ Thom . Decline of coronary heart disease mortality in the United States, Israel J . of Medical Sciences 22 :307-312, 1986 . 3 . Gillum, R .F ., A .R . Folsom and H . Blackburn . Decline in coronary heart disease mortality, Amer . J . of Medicine 76 :1055-1065, 1984 . 4 . Green, M .S ., E . Jucha and Y . Luiz . Blood pressure in smokers and nonsmokers : Epidemiologic findings, Amer . Heart Journal 111 :932-940, 1986 . 5 . Grossarth-Maticek, J . Bastiaans and D .T . Kanazir . Psychosocial factors as strong predictors of mortality from cancer, ischaemic heart disease and stroke : The Yugoslav prospective study, J . of Psychosomatic Research 29 :167-176, 1985 . 6 . Grunberg, N .E . Increased 24-hour energy expenditure in cigarette smokers, New England J . of Medicine 314 :1640, 1986 . 7 . Grunberg, N .E . Nicotine, cigarette smoking, and body weight, British Journal of Addiction, 80 :369-377, 1985 . 8. Hjermann, I ., 1 . Holme, K .V . Byre and P . Leren . Effect of diet and smoking intervention on the incidence of coronary heart disease, The Lancet, pp . 1303-1310, December 12, 1981 . 9 . Jonas, S . Increased 24-hour energy expenditure in cigarette smokers, New England J . of Medicine 314 :1640, 1986 . 10 . Lipid Research Clinics Program . The lipid research clinics coronary primary prevention trial results, JANA 251 :351-373, 1984 . 11 . Lundberg, G .D . MRFIT and the goals of The Journal, JAMA 248 :1501, 1902 . 12 . Multiple Risk Factor Intervention Trial Research Group . Multiple risk factor intervention trial : Risk factor changes and mortality results, JAMA 248 :1465-1477, 1982 . 13 . Rabkin, S .W ., E . Boyko and D .A . Streja . Relationship of weight loss and cigarette smoking to changes in high-density lipoprotein cholesterol, Amer . J . of Clinical Nutrition 34 :1764-1768, 1981 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 14 . Schatzkin, A ., L .A . Cupples . T . Heeren, S . Morelock, M . Mucatel and W .B . Kannel . The epidemiology of sudden unexpected death : Risk factors for men and women in the Framingham Heart Study, Amer . Heart Journal 107 :1300-1306, 1984 . 15 . Schulz, L_0 . Increased 24-hour energy expenditure in cigarette smokers, New England J . of Medicine 314 :1639-1640, 1986 . 16 . Theorell, T ., L . Alfredsson, S . Knox, A . Perski, J . Svensson and D . Waller . On the interplay between socioeconomic factors, personality and work environment in the pathogenesis of cardiovascular disease, Scand . J . Work Environ . Health 10 :373-380, 1984 . 17 . Wilhelmsen, L ., G . Berglund, D . Elmfeldt, 0 . Samuelson and K . Svardsudd . The multifactor primary prevention trial in Goteborg, Sweden : Comparison with a previously untreated population sample, Drugs 31(Suppl . 1) :47-51, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 LUN G 1 . Coggon, D . Trends in lung cancer mortality, Thorax 38 :721-723, 1983 . 2 . Doll, R ., R . Gray, B . Hafner and R . Peto . Mortality in relation to smoking : 22 years' observations on female British doctors, British Medical Journal, pp . 967-971, 1980 . 3 . Eckholm, E . Radon : Threat is real, but scientists argue over its severity, In : The New York Times, p . C1, September 2, 1986 . 4 . Kolonel, L .N ., M .W . Hinds, A .M .Y . Nomura, J .H . Hankin and J . Lee . Relationship of dietary vitamin A and ascorbic acid intake to the risk for cancers of the lung, bladder, and prostate in Hawaii, National Cancer Institute Monograph No . 69 :137-142, 1985 . 5 . Lee, P .N . Misclassification as a factor in passive smoking risk, The Lancet, p . 867, October 11, 1986 . 6 . Lee, P .N . Relationship of passive smoking to risk of lung cancer and other smoking-associated diseases, British J . of Cancer 54 :801-809, 1986 . 7 . McFarlane, M .J ., A .R . Feinstein and C .K . Wells . Clinical features of lung cancers discovered as a postmorten "surprise," Chest 90 :520-523, 1986 . 8 . McFarlane, M .J ., A .R . Feinstein and C .K . Wells . Necropsy evidence of detection bias in the diagnosis of lung cancer, Arch . Intern . Med . 146 :1695-1698, 1986 . 9 . McLemore, T .L ., R .R . Martin, N .P . Wray, E .T . Cantrell and D .L . Busbee . Reassessment of the relationship between aryl hydrocarbon hydroxylase and lung cancer, Cancer 48 :1438-1443, 1981 . 10 . Middleton, B ., T . Byers, J . Marshall and S . Graham . Dietary vitamin A and cancer - a multisite case-control study, Nutrition and Cancer 8 :107-116, 1986 . 11 . Nero, A .V ., M .B . Schwehr, W .W . Nazaroff and K .L . Revzan . Distribution of airborne radon-222 concentrations in U .S . homes, Science 234 :992-997, 1986 . 12 . Olsen, J .H ., O .M . Jensen and 0 . Kampstrup . Influence of smoking habits and place of residence on the risk of lung cancer among workers in one rock-wool producing plant in Denmark, Stand . J . Work Environ . Health 12(Supp . 1) :48-52, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 13. Ooi, W .L ., R .C . Elston, Y .W . Chen, J .E . Bailey-Wilson and H . Rothschild . Increased familial risk for lung cancer, J . Nat'l . Cancer Inst . 76 :217-222, 1986 . 14 . Rudiger, H .W ., D . Nowak, K . Hartmann and P . Cerutti . Enhanced formation of benzo(a)pyrene :DNA adducts in monocytes of patients with a presumed predisposition to lung cancer, Cancer Research 45:5890-5894, 1985 . 15 . Samet, J .M ., C .G . Humble and D .R . Pathak . Personal and family history of respiratory disease and lung cancer risk, Am . Rev_ Respir . Dis . 134 :466-470, 1986 . 16 . Seidegard, J . R .W . Pero, D .G . Miller and E .J . Beattie . A glutathione transferase in human leukocytes as a marker for the susceptibility to lung cancer, Carcinogenesis 7 :751-753, 1986 . 17 . Tokuhata, G .K . Familial factors in human lung cancer and smoking, Amer . J . Public Health 54 :24-32, 1964 . 18 . Williams, R .R . and J .W . Horm . Association of cancer sites wit h tobacco and alcohol consumption and socioeconomic status of patients : Interview study from the Third National Cancer Survey, J . Nat'l . Cancer Inst . 58 :525-547, 1977 . 19 . Ziegler, R .G ., T .J . Mason, A . Stemhagen, R .Hoover, J .B . Schoenberg, G . Gridley, P .W . Virgo and J .F . Fraumeni . Carotenoid intake, vegetables, and the risk of lung cancer among white men in New Jersey, Amer . J . of Epidemiology 123 :1080-1093, 1986 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 13 . Lashner, B .A ., S .B . Hanauer and M .D . Silverstein . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :645-646, 1986 . 14 . Le, M .G ., C . Hill, A . Kramar and R_ Flamant . Alcoholic beverage consumption and breast cancer in a French case-control study, Amer . J . of Epidemiology 120 :350-357, 1984 . 15 . Lesko, S .M ., L . Rosenberg, D .W . Kaufman and S . Shapiro . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :646-647, 1986 . 16 . Lesko, S .M ., L . Rosenberg, D .W . Kaufman, S .P . Helmrich, D .R . Miller, B . Strom, D . Schottenfeld, N .B . Rosenshein, R .C . Knapp, J . Lewis and S . Shapiro . Cigarette smoking and the risk of endometrial cancer, New England Journal of Medicine 313 :593-596, 1985 . 17 . MacMahon, B ., D . Trichopoulos, P . Cole and J . Brown . Cigarette smoking and urinary estrogens, New England Journal of Medicine 307 :1062-1064, 1982 . 18 . Marshall, J .R ., S . Graham, T . Byers, M_ Swanson and J . Brasure . Diet and smoking in the epidemiology of cancer of the cervix, J . of Nat'l . Cancer Inst . 70 :847-851, 1983 . 19 . McTiernan, A ., D .B . Thomas, L .K . Johnson and D . Roseman . Risk factors for estrogen receptor-rich and estrogen receptor-poor breast cancers, J_ of Nat'l . Cancer Inst . 77 :849-853, 1986 . 20 . Nordenstam, G .R . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :645, 1986 . 21 . Paffenbarger, R .S ., J .B . Kampert and H .-G . Chang . Oral contraceptives and breast cancer risk, INSERM 83 :93-114, 1979 . 22 . Ramcharan, S ., F .A . Pellegrin, R .M . Ray and J .-P . Hsu . The Walnut Creek Contraceptive Drug Study : A Prospective Study of the Side Effects of Oral Contraceptives, In : The Journal of Reproductive Medicine 25(6, Supp .) :345-372, 1980 . 23 . Ravenholt, R .T . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :646, 1986 . 24_ Rosenberg, L ., S . Shapiro, D_ Slone, D .W . Kaufman and S_ Helmrich_ breast cancer and alcoholic-beverage consumption, The Lancet, pp . 267-271, January 30, 1982 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 25 . Rosenberg, L ., P .J . Schwingl, D .W . Kaufman, D .R . Miller, S .P . Helmrich, P .D . Stolley, D . Schottenfelt and S . Shapiro . Breast cancer and cigarette smoking, New England J . of Medicine 310 :92-94, 1984 . 26 . Ross, R .K ., M .C . Pike, M .P . Vessey, D . Bull, D . Yeates and J .T . Casagrande . Risk factors for uterine fibroids : Reduced risk associated with oral contraceptives, British Medical Journal, 293 :359-362, 1986 . 27 . Smith, B .M ., M .F . Sowers and T . L . Burns . Effects of smoking on the development of female reproductive cancers, J . Nat'l . Cancer Institute 73 :371-376, 1984 . 28 . Tyler, C .W ., L .A . Webster, H .W . Ory and G .L . Rubin . Endometrial cancer : How does cigarette smoking influence the risk of women under age 55 years having this tumor? Amer . J . of Obstetrics and Gynecology 151 :899-905, 1985 . 29 . Vessey, M .P ., R . Doll, K . Jones, K . McPherson and D . Yeates . An epidemiological study of oral contraceptives and breast cancer, British Medical Journal 1 :1757-1760, 1979 . 30 . Vessy, M ., J . Baron, R . Doll, K . McPherson and 0 . Yeates . Oral contraceptives and breast cancer : Final report of an epidemiological study, British Journal of Cancer 47 :455-462, 1983 . 31 . Weiss, N .S ., V .T . Farewell, D .R . Szekely, D .R . English and N . Kiviat . Oestrogens and endometrial cancer : Effect of other risk factors on the association, Maturitas 2 :185-190, 1980 . 32 . Willett, W ., M .J . Starpfer, C . Bain, R . Lipnick, F .E . Speizer, B . Rosner, D . Cramer and C .H . Hennekens . Cigarette smoking, relative weight, and menopause, Amer . J . of Epidemiology 117 :651-658, 1983 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 ESTROGEN DEPENDEN T 1 . Baron, J .A ., T . Byers, E .R . Greenberg, K .M . Cummings and M . Swanson . Cigarette smoking in women with cancers of the breast and reproductive organs, J . Nat'l . Cancer Inst . 77 :677-680, 1986 . 2 . Baron, J .A . Smoking and estrogen-related disease, American Journal of Epidemiology 119 :9-22, 1984 . 3 . Brinton, L .A ., C . Schairer, J .L . Stanford and R .N . Hoover . Cigarette smoking and breast cancer, American Journal of Epidemiology 123 :614-622, 1986 . 4 . Burch, P .R .J . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :645, 1986 . 5 . Cramer, D .W ., E . Wilson, R .J . Stillman, M . J . Berger, S . Belisle, 1 . Schiff, B . Albrecht, M . Gibson, B .V . Stadel and S .C . Schoenbaum . The relation of endometriosis to menstrual characteristics, smoking and exercise, JAMA 255 :1904-1908, 1986 . 6 . Everson, R .B ., D .P . Sandler, A .J . Wilcox, D . Schreinemachers, D .L . Shore and C . Weinberg . Effect of passive exposure to smoking on age at natural menopause, British Medical Journal 293 :792, 1986 . 7 . Greenberg, E .R ., M . Vessey, K . McPherson and D . Yeates . Cigarette smoking and cancer of the uterine cervix, British Journal of Cancer 51 :139-141, 1985 . 8 . Hiatt, R .A . and B .H . Fireman . Smoking, menopause, and breast cancer, J . of Nat'l . Cancer Inst . 76 :833-838, 1986 . 9 . Imrey, H .H . Cigarette smoking and endometrial cancer, New England Journal of Medicine 315 :645, 1986 . 10 . Kato, I ., S . Miura, M . Yoshida and S . Tominaga . Risk factors of multiple primary cancers in breast cancer patients, Jpn . J . Cancer Res . (Gann) 77 :296-304, 1986 . 11 . Kaufman, D .W ., D . Slone, L . Rosenberg, O .S . Miettinen and S . Shapiro . Cigarette smoking and age at natural menopause, Amer . J . of Public Health 70 :420-422, 1980 . 12 . Kelsey, J .L ., V .A . LiVolsi, T .R . Hclford, D .B . Fischer, E .D . Mostow, P .E . Schwartz, T . O'Connor and C . White . A case-control study of cancer of the endometrium, Amer . J . of Epidemiology 116 :333-342, 1982 . Source: http://industrydocuments.library.ucsf.edu/tobacco/docs/kfkp0203 .m?ywaTim-3If), I "zx-?LLm?r"~If. 311-}. l- '11: ?1'an - n'v18082010?