A prospective study of tobacco use and multiple myeloma: evidence against an association

The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR]=0.9, 95 percent confidence interval [CI]=0.8–1.2) or former (RR=1.0, CI=0.8–1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR=1.0, CI=0.4–2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR=1.2, CI=0.9–1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occuring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma.Epidemiology and Biometry Program, Division of Cancer Etiology, National Cancer Institute. Westat, Inc. Rockville, MD. National Cancer Institute, 6130 Executive Blvd, Room 418, Rockville, MD 20892, USA.     

Cigarette smoking and liver cancer among US veterans

The relationship of tobacco use with risk of primary liver cancer was investigated using data from a 26-year mortality follow-up of nearly 250,000 US veterans, mostly from World War I. Significantly increased risks for liver cancer (289 deaths) were associated with most forms of tobacco use, including pipe and cigar smoking. Elevated relative tisks (RRs) were seen for current cigarette smokers (RR=2.4; 95 percent confidence interval [CI] 1.6–3.5) and former cigarette smokers (RR=1.9, 1.2–2.9). A strong dose-response relationship (P<0.001) was found for cigarette smoking, with smokers of 40 or more cigarettes per day having almost a fourfold risk (RR=3.8, 1.9–8.0). Risks were also found to increase significantly with years of cigarette use and with earlier age at the start of cigarette smoking. These results are consistent with those of other cohort and case-control studies, suggesting that cigarette smoking may be related to the risk of liver cancer.All authors are in the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute. Address correspondence to Dr Hsing at Executive Plaza North, Room 415, Bethesda, MD 20892, USA.     

Risk of gastroesophageal cancer among smokers and users of Scandinavian moist snuff

Although Scandinavian moist snuff ("snus"), no doubt, is a safer alternative to smoking, there is limited evidence against an association with gastroesophageal cancers. In a retrospective cohort study, we investigated esophageal and stomach cancer incidence among 336,381 male Swedish construction workers who provided information on tobacco smoking and snus habits within a health surveillance program between 1971 and 1993. Essentially complete follow-up through 2004 was accomplished through linkage to several nationwide registers. Multivariable Cox proportional hazards regression models estimated relative risks (RR) and 95% confidence intervals (CIs). Compared to never-users of any tobacco, smokers had increased risks for adenocarcinoma (RR = 2.3, 95% CI 1.4-3.7) and squamous cell carcinoma (RR = 5.2, 95% CI 3.1-8.6) of the esophagus, as well as cardia (RR = 2.1, 95% CI 1.5-3.0) and noncardia stomach (RR = 1.3, 95% CI 1.2-1.6) cancers. We also observed excess risks for esophageal squamous cell carcinoma (RR = 3.5, 95% CI 1.6-7.6) and noncardia stomach cancer (RR = 1.4, 95% CI 1.1-1.9) among snus users who had never smoked. Although confounding by unmeasured exposures, and some differential misclassification of smoking, might have inflated the associations, our study provides suggestive evidence for an independent carcinogenic effect of snus.     

Increased risk of colorectal cancer among smokers: Results of a 26-year follow-up of us veterans and a review

To clarify the relationship between tobacco use and risk of colorectal cancer, we evaluated a cohort of 248,046 American veterans followed prospectively for 26 years. In comparison with veterans who had never used tobacco, the risk of death was significantly increased for colon cancer and rectal cancer among current and former cigarette smokers and among pipe or cigar smokers, controlling for social class and occupational physical activity. Rectal-cancer risk was also significantly elevated among users of chewing tobacco or snuff. For both sites, risk increased significantly with pack-years, earlier age at first use, and number of cigarettes. These results reinforce 2 recent reports of the association of cigarette smoking and colorectal cancer in men and women. Inconsistencies in the findings of earlier epidemiologic studies appear to be due in large part to differences in length of follow-up or in choice of controls. Studies with at least 20 years of follow-up or population-based controls have tended to find elevated risk with tobacco smoking, while those with shorter follow-up or hospital controls have not. This, plus the strength and consistency of the association of smoking and colon polyps, suggest that smoking may primarily affect an early stage in the development of colon cancer. If this association is causal, tobacco use may be responsible for 16% of colon-cancer and 22% of rectal-cancer deaths among these veterans.     

Smoking and biliary tract cancers in a cohort of US veterans.

Except for gallstones, the risk factors for cancers of the biliary tract (CBTs) are poorly understood. Recent case-control studies have suggested cigarette smoking as a potential risk factor. In a cohort study of nearly 250,000 US veterans whose mortality was followed for up to 26 years, we evaluated the risk of CBT associated with tobacco use. Relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 303 CBT deaths were observed during the follow-up period. Compared with those who had never used any tobacco, current cigarette smokers at entry to the cohort had a 50% excess risk of CBT (RR = 1.5, CI = 1.1-2.0). A nearly 2-fold risk was observed among those who smoked more than 20 cigarettes per day and among those who started smoking under age 20. Non-significant increases in risk occurred among smokers of other forms of tobacco. This cohort study is consistent with reports that smoking is a risk factor for CBT, but further studies are needed to clarify whether the effect is specific for certain subsites and whether it reflects an association with pre-existent gallstones.     

Cigarette smoking and leukemia: results from the Lutheran Brotherhood Cohort Study

In a 20-year follow-up (1966–86) of 17,633 White males who described tobacco use in a mailed questionnaire sent in 1966, there were 74 deaths from leukemia (including 30 myeloid, 30 lymphatic, and 14 other and unspecified leukemia). Among men who ever smoked cigarettes, increased risks were observed for lymphatic (relative risk [RR]=2.7), and other and unspecified leukemia (RR=1.5); risks rose with increasing number of cigarettes smoked, although the dose-response relationship was statistically significant only for total leukemia. Mortality from myeloid leukemia was not elevated, except among those smoking over a pack of cigarettes per day. Results from this cohort support a relationship between cigarette smoking and leukemia. Further studies are needed to elucidate subtype associations with cigarette smoking.Drs Linet, McLaughlin, Hsing, Wacholder, and Blot are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Co-Chien is at Westat, Inc., Rockville, Maryland, USA, Dr Schuman is at the University of Minnesota, Minneapolis, Minnesota, USA. Dr Bjelke is with the Center for Epidemiologic Research, University of Bergen, Norway. Address correspondence to Dr Linet, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North Room 415B, Bethesda, MD 20892, USA.     

Native youth and smokeless tobacco: prevalence rates, gender differences, and descriptive characteristics

This is a report on smokeless tobacco use among Native American youth from Indian reservations in Washington State. Study findings indicate that snuff and chewing tobacco are used frequently, heavily, and at an early age by Native Americans. Nearly one-half of our subjects had used smokeless tobacco on 11 to 20 or more occasions; close to one-third of all the females had used smokeless tobacco on more than 20 occasions. Weekly users in this study were young. Of those Native subjects who used snuff or chewing tobacco weekly, 72% were under 12 years of age. Among youth who reported weekly smokeless tobacco use, about 74% of all females and 90% of all males had first used snuff or chewing tobacco before they were 10 years old. Study results have implications for efforts toward detection, treatment, and prevention of snuff and chewing tobacco use among Native American adolescents.     

Environmental tobacco smoke and lung cancer mortality in the American Cancer Society's Cancer Prevention Study II

Environmental tobacco smoke (ETS) has been classified as a human lung carcinogen by the United States Environmental Protection Agency (EPA), based both on the chemical similarity of sidestream and mainstream smoke and on slightly higher lung cancer risk in never-smokers whose spouses smoke compared with those married to nonsmokers. We evaluated the relation between ETS and lung cancer prospectively in the US, among 114,286 female and 19,549 male never-smokers, married to smokers, compared with about 77,000 female and 77,000 male never-smokers whose spouses did not smoke. Multivariate analyses, based on 247 lung cancer deaths, controlled for age, race, diet, and occupation. Dose-response analyses were restricted to 92,222 women whose husbands provided complete information on cigarette smoking and date of marriage. Lung cancer death rates, adjusted for other factors, were 20 percent higher among women whose husbands ever smoked during the current marriage than among those married to never-smokers (relative risk [RR]=1.2, 95 percent confidence interval [CI]=0.8-1.6). For never-smoking men whose wives smoked, the RR was 1.1 (CI=0.6-1.8). Risk among women was similar or higher when the husband continued to smoke (RR=1.2, CI=0.8-1.8), or smoked 40 or more cigarettes per day (RR=1.9, CI=1.0-3.6), but did not increase with years of marriage to a smoker. Most CIs included the null. Although generally not statistically significant, these results agree with the EPA summary estimate that spousal smoking increases lung cancer risk by about 20 percent in never-smoking women. Even large prospective studies have limited statistical power to measure precisely the risk from ETS.     

Oral contraceptives and primary liver cancer among young women

The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR]=1.6, 95 percent confidence interval [CI]=0.9–2.6), and for long-term (10 years) users (OR=2.0, CI=0.8–4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR=2.7, CI=1.4–5.3) and long-term users (OR=4.8, CI=1.7–14.0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives.Authors are with the Epidemiology and Biostatistics Program, Division of Cancer Etiology, National Cancer Institute, with the exception of Mr Co-Chion who is at Westat Inc., Rockville, MD, USA. Address reprint requests to Dr Hsing at the National Cancer Institute, Executive Plaza North, Room 415, Bethesda, MD 20892, USA.     

Are the known bladder cancer risk-factors associated with more advanced bladder cancer?

Risk factors for superficial and invasive bladder cancer were examined in a case-control study of 470 cases Identified in 1967–68 in the Brockton and Boston Standard Metropolitan Areas (MA, United States) and of 500 population-based controls. Histologic specimens were reviewed and classified as superficial or invasive, following a standardized protocol. The tobacco-associated risk for superficial bladder cancer was odds ratio (OR)=2.6 (95 percent confidence interval [CI]=1.7–4.1) and the risk for invasive bladder cancer was OR=1.7 (CI=1.1–2.5). For subjects less than 60 years of age, the risks were greater for invasive tumors (OR=4.3, CI=1.2–15) than for superficial tumors (OR=0, CI=0.9–4.2), but this pattern for tobacco use was not found in older subjects. A strong trend of increased risk with increased amount of cigarettes smoked was shown only for invasive bladder tumors. No clear pattern of excess risk for invasive bladder tumors was seen for age at first use and years since last use of tobacco. The risk associated with occupational exposure to aromatic amine bladder carcinogens was OR=1.7 (CI=0.8–3.3) for superficial and OR=1.5 (CI=0.8–3.0) for invasive bladder cancer. For subjects less than 60 years of age, the risks were greater for invasive (OR=12.0, CI=2.1–65) than for superficial tumors (OR=4.3, CI=0.8–24), but this pattern for occupational exposure was not found in older subjects. Risk by age at first exposure to occupational aromaticamine, bladder carcinogens was similar for superficial and invasive tumors. Overall, there was no association between known bladder-cancer risk-factors and more advanced bladder cancer. The relative risk associated with cigarette smoking and occupational exposure to aromatic amines was higher for invasive than superficial cancer only for men less than 60 years of age.Drs Hayes and Zahm are with the Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA. Authors are affiliated also with the Lucille P. Markey Cancer Center, Lexington, KN, USA (Dr Friedell) and the Department of Epidemiology, University of Alabama, Birmingham, AL, USA (Dr Cole). Address correspondence to Dr Hayes, Environmental Epidemiology Branch, National Cancer Institute, EPN 418, Bethesda, MD 20892, USA.     

A longitudinal study of smokeless tobacco use and mortality in the United States

Few studies in the United States have examined longitudinally the mortality risks associated with use of smokeless tobacco (SLT). The sample of our study was composed of participants from the National Longitudinal Mortality Study who completed a single Tobacco Use Supplement to the Current Population Survey between the years 1985 and 2011. Using survival methods, SLT use at the baseline survey was examined as a predictor of all‐cause mortality and cause‐specific mortalities in models that excluded individuals who had ever smoked cigarettes, cigars or used pipes (final n = 349,282). The participants had median and maximum follow‐up times of 8.8 and 26.3 years, respectively. Regression analyses indicated that compared to the never tobacco users, the current SLT users did not have elevated mortality risks from all cancers combined, the digestive system cancers and cerebrovascular disease. However, current SLT users had a higher mortality risk for coronary heart disease (CHD) [hazard ratio (HR) (95% CI) = 1.24 (1.05, 1.46)] relative to never tobacco users. In a separate model, the elevated risk for CHD mortality corresponded to the use of moist snuff [HR (95% CI) = 1.30 (1.03, 1.63)]. The associations with CHD mortality could be attributed to long‐term nicotine exposure, other SLT constituents (e.g., metals) or the confounding effects of CHD risk factors not accounted for in our study. The study's findings contribute to the ongoing dialogue on tobacco harm reduction and the US FDA's evaluation of Modified Risk Tobacco Product applications submitted by American SLT manufacturers.     

Smokeless tobacco and risk of head and neck cancer: Evidence from a case–control study in New England

Current studies suggesting that smokeless tobacco use increases the risk of head and neck cancer are hampered by small numbers. Consequently, there remains uncertainty in the magnitude and significance of this risk. We examined the relationship between smokeless tobacco use and head and neck squamous cell carcinoma (HNSCC) in a population‐based case–control study with 1,046 cases and 1,239 frequency‐matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI), adjusting for age, gender, race, education level, cigarette smoking, and alcohol consumption. A nonsignificant elevated association between having ever used smokeless tobacco and HNSCC risk (OR = 1.20, 95% CI: 0.67–2.16) was observed. Individuals who reported 10 or more years of smokeless tobacco use had a significantly elevated risk of HNSCC (OR = 4.06, 95% CI: 1.31–12.64), compared to never users. In an analysis restricted to never cigarette smokers, a statistically significant association was observed between ever use of smokeless tobacco and the risk of HNSCC (OR = 4.21, 95% CI: 1.01–17.57). These findings suggest that long‐term use of smokeless tobacco increases the risk of HNSCC.     

Tobacco use and prostate cancer in Blacks and Whites in the United States

Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR]=1.1, 95 percent confidence interval [CI]=0.7–1.5) and in Whites (OR=1.2, CI=0.9–1.6), or for current cigarette smokers, in Blacks (OR=1.0, CI=0.7–1.4) and in Whites (OR=1.2, CI=0.8–1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR=1.4, CI=1.0–1.5) and current (OR=1.5, CI=1.0–2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR=1.5, CI=1.0–2.3) and former (OR=1.7, CI=1.1–2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking. Risks also were not elevated for former or current users of pipes, cigars, or chewing tobacco, but the risk associated with current snuff use was OR=5.5 (CI=1.2–26.2). This subgroup finding may have been due to chance. The results of the present study may be consistent with a small excess risk for prostate cancer associated with tobacco use, but the lack of consistent findings in population subgroups and the lack of a clear dose-response relationship argue more strongly that no causal association exists. The data do not indicate that the Black-White difference in prostate cancer risk is related to tobacco use.This research was performed under contracts: NO1-CP-51090, NO1-CN-0522, NO1-CP-51089, NO1-CN-31022, NO1-CP-51092, and NO1-CN-5227.     

A prospective study of cigarette tar yield and lung cancer

We examined the relationship of cigarette tar yield and other cigarette-usage characteristics in current smokers to the incidence of lung cancer in a study population of 79,946 Kaiser Permanente Medical Care Program members, aged 30–89 years, who completed a detailed, self-administered, smoking-habit questionnaire during the years 1979 through 1985. Mean length of follow-up was 5.6 years. There were 302 incident lung cancers, of which 89 percent occurred in current or former smokers. The tar yield of the current cigarette brand was unassociated with lung cancer incidence (relative risk [RR]=1.02 per 1 mg tar-yield in men, 95 percent confidence interval [CI]=0.98–1.05; RR=0.99, CI=0.96–1.03 in women). However, in long-term (>20 years) smokers, the risk of lung cancer was decreased in women who had smoked filtered cigarettes for 20 or more years relative to lifelong smokers of unfiltered cigarettes (RR=0.36, CI=0.18–0.75), but not in men who had smoked filtered cigarettes for 20 or more years (RR=1.04, CI=0.58–1.87).Authors are with the Division of Research, Kaiser Permanente Medical Care Program, 3451 Piedmont Avenue, Oakland, CA 94611, USA. Address correspondence to Dr Sidney. This study was funded by grants R01 CA 36074 and R35 CA 49761 from the US National Cancer Institute.     

Occupational cancer mortality among urban women in the former USSR

Occupational cancer mortality was evaluated among approximately three million female pensioners from urban areas of the former USSR. In 1970, these women experienced 14,918 cancer deaths. Occupational data were obtained from death certificates and the 1970 USSR National Population Census. Thirty-five occupational groups, including nine predominantly professional or office-work groups and 26 groups involving physical labor, were evaluated. The expected mortality rates were based on the urban female population of the USSR in 1970. Data for all cancer sites combined, and cancers of the esophagus, stomach, colon, rectum, lung, breast, cervix, and hematopoietic system are presented. Among all female pensioners, there were significant increases of all cancers combined (rate ratio [RR]=1.05), and cancers of the breast (RR=1.3), cervix (RR=1.3), and the hematopoietic system (RR=1.2), and a significant deficit of cancer of the esophagus (RR=0.8). Many well-established associations between cancer and occupation among men were observed among the study group of female pensioners, such as stomach and lung cancer among miners, and hematopoietic malignancies among scientists and physicians. Other associations, to be investigated further, also were observed, such as excess lung cancer among waitresses. The peak employment period for this cohort of women was during World War II and the postwar period, when Soviet women outnumbered men almost two-to-one. Consequently, many of the women held jobs that are typically held by men. Thus, this study provides valuable information on occupational risks to women that may be relevant in other countries where women increasingly are being employed in jobs traditionally held by men.Due to recent events, the United Soviet Socialist Republics (USSR) no longer exists as a political entity. For simplicity and bistorical accuracy, bowever, the text generally refers to the USSR and Soviet institutions that were so named when the study was conducted.Drs Bulbulyan and Zaridze are with the Department of Cancer Epidemiology, Institute of Carcinogenesis, All-Union Oncological Research Center, Academy of Medical Sciences, Moscow, Russia. Dr Zahm, to whom correspondence should be addressed, is with the Occupational Studies Section, Environmental Epidemiology Branch, National Cancer Institute, Executive Plaza North, Room 418, Rockville, MD 20892, USA.     

Two large prospective studies of mortality among men who use snuff or chewing tobacco (United States)

Background: Few prospective studies have examined the health risks associated with use of snuff and chewing tobacco.Methods: We studied the association between the use of spit tobacco (snuff or chewing tobacco) and mortality among men enrolled in Cancer Prevention Study I (CPS-I) in 1959 or Cancer Prevention Study II (CPS-II) in 1982. Analyses were based on men who reported exclusive use of snuff or chewing tobacco (7745 in CPS-I, 3327 in CPS-II) or no previous use of any tobacco product (69,662 in CPS-I, 111,482 in CPS-II) at baseline. Twelve-year follow-up of CPS-I, and 18-year follow-up of CPS-II identified 11,871 and 19,588 deaths, respectively. Cox proportional hazards models were used to control for age and other covariates.Results: Men who currently used snuff or chewing tobacco at baseline had higher death rates from all causes than men who did not in both CPS-I (hazard ratio [HR]=1.17, 95% CI=1.11–1.23) and CPS-II (HR=1.18, 95% CI=1.08–1.29). In CPS-I, current use of spit tobacco was statistically significantly associated with death from coronary heart disease (CHD), stroke, and diseases of the respiratory, digestive, and genitourinary systems, but not with death from cancer. In CPS-II, use of these products was significantly associated with death from CHD, stroke, all cancers combined, lung cancer, and cirrhosis. The associations with cardiovascular and other non-malignant endpoints were attenuated, but not eliminated, by controlling for measured covariates. Former use of spit tobacco was not associated with any endpoint in CPS-II. No clear dose response was observed with either the frequency or duration of usage for any endpoint.Conclusions: These two prospective studies provide limited evidence that current use of chewing tobacco or snuff may increase mortality from heart disease and stroke.     

Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma

Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR]=1.4), high-grade lymphoma (OR=2.3), and unclassified lymphoma (OR=2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma.Ms Brown and Dr Blair are with the Epidemiology and Biostatistics Program, National Cancer Institute. Dr Everett is with the Department of Internal Medicine, Orlando Regional Medical Center, Orlando, FL, USA. Drs Gibson and Schuman are in the Department of Epidemiology, University of Minnesota, Minneapolis, MN, USA. Dr Burmeister is in the Department of Preventive Medicine, University of Iowa, Iowa City, IA, USA. Address correspondence to Ms Brown, Epidemiology and Biostatistics Program, National Cancer Institute, Executive Plaza North, Room 415C, Bethesda, MD 20892, USA. This work was supported in part by a grant from the National Institute of Environmental Health Sciences (ES 03099).     

Cigarette smoking,use of other tobacco products and stomach cancer mortality in US adults: The Cancer Prevention Study II

Cigarette smoking is associated with increased risk of stomach cancer in many studies but there are limited data on this relationship in women and on risk associated with use of tobacco products other than cigarettes. We examined stomach cancer death rates in relation to cigarette smoking in women and use of cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective mortality study in the United States (US). Cohort follow-up from 1982-96 identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women, respectively. Cox proportional hazards models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent group. Multivariate-adjusted RRs were the highest for men who currently smoked cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75-2.67) and both increased with smoking duration. Women who currently (RR = 1.49, 95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes were at significantly increased risk, as were men who formerly smoked cigarettes (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men who reported a history of chronic indigestion or gastroduodenal ulcer had substantially higher mortality rates associated with current cigarette (RR = 3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as did men who were current aspirin users. If causal, the estimated proportion of stomach cancer deaths attributable to tobacco use would be 28% in US men and 14% in women. We conclude that prolonged use of tobacco products is associated with increased stomach cancer mortality in men and women. The accumulated evidence from this and other studies support reconsidering stomach cancer as a tobacco-related cancer.     

Smokeless tobacco: association with increased cancer risk

Smokeless tobacco (chewing tobacco and snuff) contains known carcinogens shown to increase the risk for oral cancer. The effect of snuff has been more fully documented than other forms of smokeless tobacco, although the carcinogenic potential of all such products is acknowledged. Risk increases with increasing length of exposure, with risks greatest for anatomic sites where the product has been held in contact the longest time. In some studies, other organs, such as the esophagus, larynx, and stomach, have been shown to be at increased risk for cancer from the use of smokeless tobacco, although at present the data are insufficient to substantiate fully a causal association. Numerous reports have shown an association between snuff use and leukoplakia, with less evidence at present linking chewing tobacco use with leukoplakia. The documented early onset of the smokeless tobacco habit and reports of increases in certain oral cancers among young men raise serious concerns of an impending oral cancer epidemic in this population. In addition, synergistic interactions with other oral cancer risk factors, e.g., smoking and alcohol, and a high rate for second primaries observed for these cancers add to the concern. Unless the tide of its use is stemmed, long-term use can be expected to produce an increase in oral cancers, and perhaps cancers of other sites, as youthful users mature and accumulate exposure to this carcinogenic agent.