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Background: Although several epidemiological studies have examined the mortality among users of spit tobacco, none have compared mortality of former cigarette smokers who substitute spit tobacco for cigarette smoking (“switchers”) and smokers who quit using tobacco entirely. Methods: A cohort of 116 395 men were identified as switchers (n = 4443) or cigarette smokers who quit using tobacco entirely (n = 111 952) when enrolled in the ongoing US American Cancer Society Cancer Prevention Study II. From 1982 to 31 December 2002, 44 374 of these men died. The mortality hazard ratios (HR) of tobacco-related diseases, including lung cancer, coronary heart disease, stroke and chronic obstructive pulmonary disease, were estimated using Cox proportional hazards regression modelling adjusted for age and other demographic variables, as well as variables associated with smoking history, including number of years smoked, number of cigarettes smoked and age at quitting. Results: After 20 years of follow-up, switchers had a higher rate of death from any cause (HR 1.08, 95% confidence interval (CI) 1.01 to 1.15), lung cancer (HR 1.46, 95% CI 1.24 to 1.73), coronary heart disease (HR 1.13, 95% CI 1.00 to 1.29) and stroke (HR 1.24, 95% CI 1.01 to 1.53) than those who quit using tobacco entirely. Conclusion: The risks of dying from major tobacco-related diseases were higher among former cigarette smokers who switched to spit tobacco after they stopped smoking than among those who quit using tobacco entirely.

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.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for ≥60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for ≥60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (≥30 pills per month for ≥5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.

Physical activity has consistently been associated with lower risk of colon cancer, but information is limited on the amount, type, and timing of activities. The relationship between physical activity and rectal cancer is unclear. We examined characteristics of recreational physical activity in relation to colon and rectal cancer in the Cancer Prevention Study II Nutrition Cohort of 70,403 men and 80,771 women (median age, 63 years); 940 colon and 390 rectal cancers were identified from enrollment in 1992 to 1993 through August 1999. The multivariate-adjusted rate ratios (95% confidence intervals) associated with any recreational physical activity compared with none were 0.87 (0.71-1.06) for colon cancer and 0.70 (0.53-0.93) for rectal cancer. Colon cancer risk decreased significantly with increasing total hours (P for trend without reference group = 0.007) and metabolic equivalent hours (P for trend = 0.006) per week of activities. No clear decrease in rectal cancer risk was seen with increasing hours per week of physical activity. Rate ratios (95% confidence intervals) were 0.72 (0.52-0.98) for

Objectives. We examined the prevalence of endoscopy (sigmoidoscopy or colonoscopy) by indication and by demographic and lifestyle factors. Methods. We analyzed cross-sectional data collected in 1997 from participants aged 50 years and older in the Cancer Prevention Study (CPS) II Nutrition Cohort. Results. Fifty-eight percent of men and 51% of women reported ever having undergone endoscopy; only 42% of men and 31% of women reported endoscopy for screening rather than for disease diagnosis or follow-up. Prevalence varied by demographic and lifestyle factors. Conclusions. Efforts to increase colorectal cancer screening need to target women, all persons aged 50–64 years, and those with colorectal cancer risk factors. Future studies should distinguish endoscopy for screening from procedures for disease diagnosis and follow-up to avoid overestimating screening compliance.

Some epidemiologic studies suggest that use of vitamin C or vitamin E supplements, both potent antioxidants, may reduce the risk of bladder cancer. The authors examined the association between use of individual vitamin C and vitamin E supplements and bladder cancer mortality among 991,522 US adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a self-administered questionnaire at enrollment in 1982 and were followed regarding mortality through 1998. During follow-up, 1,289 bladder cancer deaths occurred (962 in men and 327 in women). Rate ratios were adjusted for age, sex, cigarette smoking, education, and consumption of citrus fruits and vegetables. Regular vitamin C supplement use (or=15 times per month) was not associated with bladder cancer mortality, regardless of duration (rate ratio (RR) = 0.91, 95% confidence interval (CI): 0.68, 1.20 for10 years' use; RR = 1.25, 95% CI: 0.91, 1.72 foror=10 years' use). Regular vitamin E supplement use foror=10 years was associated with a reduced risk of bladder cancer mortality (RR = 0.60, 95% CI: 0.37, 0.96), but regular use of shorter duration was not (RR = 1.04, 95% CI: 0.77, 1.40). Results support the hypothesis that long-duration vitamin E supplement use may reduce the risk of bladder cancer mortality.

Objective: Multivitamins contain several nutrients, including folic acid, which are hypothesized to reduce colon cancer risk. Previous epidemiologic studies have suggested that effects of multivitamins containing substantial amounts of folic acid (introduced in 1973) may not be evident until 15 or more years since first use. Methods: We examined the association between daily multivitamin use and colon cancer mortality among 806,397 US men and women in the Cancer Prevention Study II cohort who completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. Results: After multivariate adjustment, multivitamin use at enrollment showed little association with colon cancer mortality. After 15 years since first use of a multivitamin potentially containing folic acid, we observed slightly decreased risk of colon cancer mortality (rate ratio (RR) = 0.89, 95% confidence interval (CI) 0.80–0.99). Consistent with previous reports, this association was stronger among participants consuming two or more alcoholic drinks per day (RR = 0.71, 95% CI 0.56–0.91). Conclusion: Our results are consistent with a modest reduction in colon cancer mortality associated with use of folic acid-containing multivitamins among moderate to heavy alcohol users.

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly known as statins, account for most cholesterol-lowering drug use in the United States. A recent large case-control study reported that use of statins for more than 5 years was associated with a 47% reduction in risk of colorectal cancer. No other large studies have examined this association. We examined the association between use of cholesterol-lowering drugs and colorectal cancer incidence among 132,136 men and women in the Cancer Prevention Study II Nutrition Cohort. We identified 815 incident cases of colorectal cancer among study participants during follow-up from the date of completion of a study questionnaire in 1997 through August 31, 2001. Current use of cholesterol-lowering drugs was not associated with colorectal cancer incidence (multivariable adjusted rate ratio [RR] = 1.03, 95% confidence interval [CI] = 0.85 to 1.26). Current use of cholesterol-lowering drugs for 5 years or more was also not associated with colorectal cancer incidence (multivariable adjusted RR = 1.09, 95% CI = 0.83 to 1.43). Our results do not support the hypothesis that statin use strongly reduces risk of colorectal cancer. However, we cannot rule out a small reduction in risk or an effect associated with only specific types or doses of statins.

SERIES “THE GLOBAL BURDEN OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE” Edited by K.F. Rabe and J.B. Soriano Number 1 in this Series Chronic obstructive pulmonary disease (COPD) is a leading but under-recognised cause of morbidity and mortality worldwide 1. The prevalence of COPD in the general population is estimated to be ∼1% across all ages rising steeply to >10% amongst those aged ≥40 yrs. The prevalence climbs appreciably higher with age. The 30-yr projections for the global increase in COPD from 1990–2020 are startling. COPD is projected to move from the sixth to the third most common cause of death worldwide, whilst rising from fourth to third in terms of morbidity within the same time-frame 2. The cofactors responsible for this remarkable increase are the continued use of tobacco, coupled with the changing demographics of the world, such that many more people, especially those in developing countries, are living into the COPD age range. COPD is under-diagnosed not only in its early stages, but even when lung function is severely impaired. This is perhaps surprising, since simple and inexpensive spirometers that are suitable in clinical practice are now available, and lung function is a powerful predictor of all-cause mortality, regardless of smoking status. No other disease that is responsible for comparable morbidity, mortality and cost is neglected by healthcare providers as much as COPD. It may well be that the true burden of the disease is not fully appreciated, and the message that COPD is both preventable and treatable has yet to be fully understood by most healthcare providers. The hope is that highlighting these facts will help to raise the profile of COPD and begin to change long-held attitudes. Up to 2001, only 32 prevalence surveys of COPD had been reported 3. This is remarkable given the hundreds …

Background: Use of aspirin and other nonsteroidal antiinfl ammatory drugs (NSAIDs) has consistently been associated with a reduced risk of colon cancer. Recent epidemiologic studies have suggested that the use of NSAIDs, particularly aspirin, may also be associated with a reduced risk of prostate cancer, but the evidence remains limited. Methods: We examined the association between NSAID use and prostate cancer incidence among 70 144 men in the American Cancer Society’s Cancer Prevention Study II Nutrition Cohort. Information on NSAID use was obtained from a questionnaire completed at study enrollment in 1992 – 1993 and was updated using follow-up questionnaires in 1997 and 1999. We calculated rate ratios (RRs) and 95% confi dence intervals (CIs) for prostate cancer incidence associated with NSAID use, adjusting for age and potential prostate cancer risk factors. Results: During follow-up from 1992 – 1993 through August 31, 2001, 4853 cases of incident prostate cancer were identifi ed. Neither current aspirin use nor current use of NSAIDs (aspirin and other NSAIDs combined) was associated with prostate cancer risk, even at the highest usage level (60 or more pills per month). However, long-duration regular use (30 or more pills per month for 5 or more years) of NSAIDs was associated with reduced risk of prostate cancer (RR = 0.82, 95% CI = 0.71 to 0.94). Longduration regular use of aspirin was also associated with reduced risk of prostate cancer (RR = 0.85, 95% CI = 0.73 to 0.99). The absolute rate of prostate cancer (standardized to the age distribution of study participants using 5-year age categories) was 1013 per 100 000 person-years among men who had never reported NSAID use, and 847 per 100 000 person-years among long duration regular NSAID users. Conclusions: These results support the hypothesis that long duration regular NSAID use is associated with modestly reduced risk of prostate cancer. [J Natl Cancer Inst 2005;97:975 – 80]

Background: Results from some epidemiologic studies have suggested that aspirin use may reduce risk of pancreatic cancer, but the evidence remains limited. Methods: We examined the association between aspirin use and pancreatic cancer mortality among 987 590 U.S. adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a self-administered questionnaire in 1982 and were followed for mortality through 2000. During follow-up, there were 4577 deaths from pancreatic cancer (2434 in men and 2143 in women). We calculated rate ratios (RR) adjusted for age, sex, race, body mass index, diabetes, and cigarette smoking status. Results: Aspirin use was not associated with pancreatic cancer mortality. The rate ratio associated with aspirin use 30 or more times per month, compared with no use, was 0.97 (95% confi dence interval [CI] 0.86 to 1.09). Even participants who reported both frequent aspirin use (>30 times per month) and use for 20 or more years were not at decreased risk compared with nonusers (RR 0.96, 95% CI 0.69 to 1.33). We found no association between aspirin use and pancreatic cancer mortality in subgroup analyses by follow-up time, cigarette smoking status, or sex. Conclusion: Results from this large prospective study do not support an important effect of aspirin use on pancreatic cancer mortality. [J Natl Cancer Inst 2004;96:524 – 8]

Multivitamins contain several nutrients, including folic acid, that are hypothesized to reduce the risk of colorectal cancer. Previous studies suggest that multivitamin use may reduce colorectal cancer risk but only after a long latency period. The authors examined the association between regular multivitamin use (four or more times per week) and colorectal cancer incidence among 145,260 men and women in the Cancer Prevention Study II Nutrition Cohort. Current multivitamin use was reported on a questionnaire at enrollment in 1992-1993. All participants had also reported multivitamin use on a questionnaire completed for a different study approximately 10 years earlier (in 1982). The authors observed 797 incident cases of colorectal cancer during follow-up from 1992 to 1997. After multivariate adjustment, regular multivitamin use at enrollment was not associated with risk of colorectal cancer (rate ratio = 1.04, 95% confidence interval: 0.87, 1.23), whereas regular multivitamin use 10 years before enrollment was associated with reduced risk (rate ratio = 0.71, 95% confidence interval: 0.57, 0.89). Regular multivitamin users 10 years before enrollment were at similarly reduced risk whether they were still regular multivitamin users at enrollment or had stopped. These results are consistent with the hypothesis that past, but not recent, multivitamin use may be associated with modestly reduced risk of colorectal cancer.

Supplementation with antioxidant vitamins has been associated with decreased risk of stomach cancer or regression of precancerous lesions in high-risk areas of China and Colombia. We examined the association between stomach cancer mortality and regular use (or =15 times per month) of individual vitamin C supplements, individual vitamin E supplements, and multivitamins among 1,045,923 United States adults in the Cancer Prevention Study II (CPS-II) cohort. CPS-II participants completed a questionnaire at enrollment in 1982 and were followed for mortality through 1998. During follow-up, there were 1,725 stomach cancer deaths (1,127 in men and 598 in women). After adjustment for multiple potential stomach cancer risk factors, vitamin C use at enrollment was associated with reduced risk of stomach cancer mortality [rate ratio (RR), 0.83; 95% confidence interval (CI), 0.68-1.01]. However, this reduction in risk was observed only among participants with short duration use at enrollment (RR, 0.68; 95% CI, 0.51-0.91 for10 years of use; RR, 1.00; 95% CI, 0.73-1.38 foror =10 years of use). There was no association between stomach cancer mortality and regular use of vitamin E (RR, 1.02; 95% CI, 0.82-1.27) or multivitamins (RR, 0.89; 95% CI, 0.77-1.03), regardless of duration of use. Our results suggest that the use of vitamin C, vitamin E, or multivitamin supplements may not substantially reduce risk of stomach cancer mortality in North American populations in which stomach cancer rates are relatively low. Our results do not rule out effects of vitamin supplementation in areas in which stomach cancer rates are high and stomach cancer etiology may differ.

Consumption of red and processed meat has been associated with colorectal cancer in many but not all epidemiological studies; few studies have examined risk in relation to long-term meat intake or the association of meat with rectal cancer.To examine the relationship between recent and long-term meat consumption and the risk of incident colon and rectal cancer.A cohort of 148 610 adults aged 50 to 74 years (median, 63 years), residing in 21 states with population-based cancer registries, who provided information on meat consumption in 1982 and again in 1992/1993 when enrolled in the Cancer Prevention Study II (CPS II) Nutrition Cohort. Follow-up from time of enrollment in 1992/1993 through August 31, 2001, identified 1667 incident colorectal cancers. Participants contributed person-years at risk until death or a diagnosis of colon or rectal cancer.Incidence rate ratio (RR) of colon and rectal cancer.High intake of red and processed meat reported in 1992/1993 was associated with higher risk of colon cancer after adjusting for age and energy intake but not after further adjustment for body mass index, cigarette smoking, and other covariates. When long-term consumption was considered, persons in the highest tertile of consumption in both 1982 and 1992/1993 had higher risk of distal colon cancer associated with processed meat (RR, 1.50; 95% confidence interval [CI], 1.04-2.17), and ratio of red meat to poultry and fish (RR, 1.53; 95% CI, 1.08-2.18) relative to those persons in the lowest tertile at both time points. Long-term consumption of poultry and fish was inversely associated with risk of both proximal and distal colon cancer. High consumption of red meat reported in 1992/1993 was associated with higher risk of rectal cancer (RR, 1.71; 95% CI, 1.15-2.52; P = .007 for trend), as was high consumption reported in both 1982 and 1992/1993 (RR, 1.43; 95% CI, 1.00-2.05).Our results demonstrate the potential value of examining long-term meat consumption in assessing cancer risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.