Prospective study of chemical exposures and amyotrophic lateral sclerosis.

BACKGROUND: Although environmental toxins, including pesticides, are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), no data exist from large prospective investigations. This study assessed the association between exposure to chemicals and risk of ALS in a prospective cohort study. METHODS: The relation between self-report of regular exposure to 11 different chemical classes or x rays and ALS mortality among over 1 million participants in the American Cancer Society's Cancer Prevention Study II was prospectively assessed. Follow-up from 1989 through 2004 identified 617 deaths from ALS among men and 539 among women. Adjusted rate ratios (RR) were calculated using Cox proportional hazards. RESULTS: The RR for ALS mortality among individuals exposed to pesticides/herbicides compared with that among unexposed individuals was 1.07 (95% CI 0.79 to 1.44), but somewhat higher after excluding those with missing duration of pesticides exposure (RR 1.44; 95% CI 0.89 to 2.31; p = 0.14). A non-significant increase in ALS mortality was found among individuals who reported exposure to formaldehyde (RR 1.34; 95% CI 0.93 to 1.92). Excluding those with a missing duration of formaldehyde exposure, the RR was 2.47 (95% CI 1.58 to 3.86), and there was a strongly significant dose-response relation with increasing years of exposure (p trend = 0.0004). CONCLUSIONS: There was little evidence for any association between pesticides/herbicide exposure and ALS. In contrast, evidence was found, suggesting an increased risk of ALS with formaldehyde exposure. Because of the longitudinal design, this result is unlikely to be due to bias, but it should nevertheless be interpreted cautiously and needs to be verified independently.

Temporal relationship between cigarette smoking and risk of Parkinson disease.

OBJECTIVE: To characterize further the relationship between smoking history and Parkinson disease (PD) risk by considering temporal and qualitative features of smoking exposure, including duration, average intensity, and recentness, as well as the relative importance of smoking during different periods of life. METHODS: We prospectively assessed incident PD from 1992 to 2001 among 79,977 women and 63,348 men participating in the Cancer Prevention Study II Nutrition Cohort, according to their cigarette smoking status and lifetime smoking histories. RESULTS: During follow-up, 413 participants had definite or probable PD confirmed by their treating neurologists or medical record review. Compared with never smokers, former smokers had a relative risk (RR) of 0.78 (95% CI 0.64 to 0.95) and current smokers had an RR of 0.27 (95% CI 0.13 to 0.56). On average, participants with more years smoked, more cigarettes per day, older age at quitting smoking, and fewer years since quitting smoking had lower PD risk. The relative risks and trends did not vary significantly by sex. The cumulative incidence of PD was lowest among participants who quit smoking at later ages. A 30% to 60% decreased risk of PD was apparent for smoking as early as 15 to 24 years before symptom onset, but not for smoking 25 or more years before onset. CONCLUSIONS: The lower risk of Parkinson disease among current and former smokers varied with smoking duration, intensity, and recentness. The dependence of this association on the timing of smoking during life is consistent with a biologic effect.

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Prospective study of occupation and amyotrophic lateral sclerosis mortality.

Occupational exposures are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), but results of epidemiologic studies have been inconsistent. The authors prospectively assessed the relation between occupation and ALS mortality among more than 1 million participants in the Cancer Prevention Study II of the American Cancer Society. Follow-up from 1989 through 2002 identified 507 ALS deaths among men and 430 among women. Adjusted rate ratios were calculated by using Mantel-Haenszel weights and Cox proportional hazards. Among men, elevated ALS mortality was found for programmers (rate ratio = 4.55, 95% confidence interval: 1.46, 14.2; p = 0.009) and laboratory technicians (rate ratio = 1.96, 95% confidence interval: 1.04, 3.66; p = 0.04). Occupations previously associated with increased risk of ALS for which no increased risk was found included farmers, electricians, and welders, although the numbers of electricians (eight ALS deaths) and welders (two ALS deaths) were small. Among women, only machine assemblers had significantly increased ALS mortality (rate ratio = 2.81, 95% confidence interval: 1.05, 7.53; p = 0.04). Results, which suggest that male programmers and laboratory technicians and female machine assemblers may be at increased risk of death from ALS, should be interpreted cautiously, however, because they are based on small numbers.

Prospective study of military service and mortality from ALS.

BACKGROUND: Two recent studies suggest that the risk of ALS is increased among Gulf War veterans. It is not known whether military service outside of the Gulf War is associated with increased risk of ALS. METHODS: The authors prospectively assessed the relation between service in the military and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort that includes over 500,000 men from the 50 states, Washington, DC, and Puerto Rico. Participant follow-up was conducted from 1989 through 1998 for ALS mortality. There were a total of 280 deaths from ALS among 126,414 men who did not serve in the military and 281,874 who did. Adjusted relative risks (RRs) were calculated using Mantel-Haenszel weights and Cox proportional hazards. RESULTS: Men who served in the military had an increased death rate from ALS (RR = 1.53; 95% CI: 1.12 to 2.09; p = 0.007) compared with those who did not serve. The increase in ALS mortality was observed among men who served in the Army or National Guard (RR = 1.54), Navy (RR = 1.87), Air Force (RR = 1.54), and Coast Guard (RR = 2.24); no increase in risk was found in men who served in the Marine Corps, although there were only 13,670 men in this group. The risk of ALS among men who served was elevated in every 5-year birth cohort from 1915 through 1939. CONCLUSIONS: Military personnel have an increased risk of ALS. This increase appeared to be largely independent of the branch of service and the time period served.

Prospective study of cigarette smoking and amyotrophic lateral sclerosis.

Cigarette smoking has been proposed as a risk factor for amyotrophic lateral sclerosis (ALS), but because of the low incidence of ALS this association has been examined only with case-control methods. The authors prospectively assessed the relation between cigarette smoking and ALS mortality among participants in the Cancer Prevention Study II cohort of the American Cancer Society, a cohort of over 1 million people enrolled in 1982 who completed a lifestyle questionnaire including a detailed smoking history at baseline. Causes of deaths were ascertained through death certificates; ALS was not identified separately until 1989. From January 1, 1989, through 1998, 291 women and 330 men died from ALS. The relative risk of ALS among current smokers compared with never smokers was 1.67 (95% confidence interval: 1.24, 2.24; p = 0.002) in women and 0.69 (95% confidence interval: 0.49, 0.99; p = 0.04) in men. The difference in the relative risk estimates between the sexes was statistically significant (p < 0.0003). This large prospective study provides limited evidence that current cigarette smoking may be associated with increased death rates from ALS in women but not in men.

Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease.

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.

A prospective study of diet and stomach cancer mortality in United States men and women.

Frequent consumption of fruits, vegetables, and whole grains has been associated with a reduced risk of stomach cancer in the majority of case-control studies of these factors: however, prospective studies have been less consistent. We examined the association between selected major food groups (citrus fruits, vegetables, whole grains, and processed meats) and risk of fatal stomach cancer in the Cancer Prevention Study (CPS) II cohort of 1.2 million United States men and women. During 14 years of follow-up, we documented 439 stomach cancer deaths in women and 910 in men after exclusion of individuals with prevalent cancers, inadequate diet information, and recent weight loss at baseline in 1982. After controlling for other risk factors, none of the food groups examined were associated with risk of stomach cancer except for an unexpected increased risk with vegetable consumption in women [relative risk (RR) = 1.25; 95% confidence interval (CI), 0.99-1.58; highest versus lowest tertile, P = 0.06 for trend]. A high overall plant food intake (a sum of vegetables, citrus fruit, and whole grains) was associated with reduced risk in men (RR = 0.79; 95% CI, 0.67-0.93; highest versus lowest tertile, P = 0.003 for trend), but not in women (RR = 1.18; 95% CI, 0.93-1.50; P = 0.16 for trend). Of individual foods examined, liver consumption greater than twice/week was associated with an increased risk of fatal stomach cancer in women (RR = 1.96; 95% CI, 1.09-3.53) and men (RR = 1.63; 95% CI, 1.02-2.62) compared with nonconsumers. This study supports a modest role for plant foods in reducing the risk of fatal stomach cancer in men, but not in women.

Determinants of DNA yield and quality from buccal cell samples collected with mouthwash.

Buccal cells are becoming an important source of genomic DNA in epidemiological studies, but little is known about the effect of different sampling conditions on DNA quality and yield. We used a mouthwash protocol to collect six daily buccal cell samples from 35 healthy volunteers. Twenty-four individuals (six men and 18 women) correctly completed the protocol and were included in paired analyses to determine whether "swish" time (30 s versus 60 s), toothbrushing before collection, or lag time between collection and DNA extraction (1 day versus 5, 10, or 30 days at room temperature) would affect sample quality and yield. Total DNA, human-specific DNA (hDNA), degradation of DNA, and ability to amplify by PCR were determined. hDNA yield did not significantly vary by "swish" time. However, toothbrushing 1 h before sample collection reduced the amount of hDNA by nearly 40% (34 microg versus 21 microg; P = 0.06). Median hDNA yields for samples that were held for 1, 5, 10, and 30 days before extraction were 32 microg (range, 4-196), 32 microg (2-194), 23 microg (3-80), and 21 microg (5-56), respectively. The 10- and 30-day samples had significantly less hDNA than those processed after 1 day (P = 0.01). PCR success rates for beta-globin gene fragments of length 268 bp, 536 bp, and 989 bp were 94% or better, and high molecular weight DNA (>23 kb) was found in all but one sample. These results suggest that buccal cells should be collected before brushing teeth and processed within 5 days of collection to maximize hDNA yield.

Cigarette smoking and diabetes mellitus: evidence of a positive association from a large prospective cohort study.

OBJECTIVE: Only a few prospective studies have examined the relationship between the frequency of cigarette smoking and the incidence of diabetes mellitus. The purpose of this study was to determine whether greater frequency of cigarette smoking accelerated the development of diabetes mellitus, and whether quitting reversed the effect. METHODS: Data were collected in the Cancer Prevention Study I, a prospective cohort study conducted from 1959 through 1972 by the American Cancer Society where volunteers recruited more than one million acquaintances in 25 US states. From these over one million original participants, 275,190 men and 434,637 women aged > or = 30 years were selected for the primary analysis using predetermined criteria. RESULTS: As smoking increased, the rate of diabetes increased for both men and women. Among those who smoked > or = 2 packs per day at baseline, men had a 45% higher diabetes rate than men who had never smoked; the comparable increase for women was 74%. Quitting smoking reduced the rate of diabetes to that of non-smokers after 5 years in women and after 10 years in men. CONCLUSIONS: A dose-response relationship seems likely between smoking and incidence of diabetes. Smokers who quit may derive substantial benefit from doing so. Confirmation of these observations is needed through additional epidemiological and biological research.

Vitamin supplement use and fatal non-Hodgkin's lymphoma among US men and women.

The authors evaluated the association between use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma in a large prospective mortality study of US men and women. During 14 years of follow-up (1982-1996), 1,571 non-Hodgkin's lymphoma deaths among 508,351 men and 1,398 non-Hodgkin's lymphoma deaths among 676,306 women were documented. Long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins was unrelated to fatal non-Hodgkin's lymphoma among either men or women. The multivariate relative risks for men who used supplements for 10 or more years were 1.03 (95% confidence interval (CI): 0.54, 2.00) for vitamin A supplements, 1.04 (95% CI: 0.78, 1.39) for vitamin C supplements, 1.06 (95% CI: 0.74, 1.51) for vitamin E supplements, and 1.14 (95% CI: 0.92, 1.40) for multivitamins. The multivariate relative risks for women who used supplements for 10 or more years were 1.40 (95% CI: 0.77, 2.54) for vitamin A supplements, 1.19 (95% CI: 0.89, 1.60) for vitamin C supplements, 1.27 (95% CI: 0.87, 1.84) for vitamin E supplements, and 1.21 (95% CI: 0.98, 1.50) for multivitamins. All associations became weaker when vitamin supplements were mutually adjusted. These findings do not support an important relation between long-term regular use of individual supplements of vitamins A, C, and E only and multivitamins and fatal non-Hodgkin's lymphoma.

Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States.

Body weight and height have both been associated consistently with postmenopausal breast cancer but less consistently with prostate cancer. The present study examined the relationship between body mass index (BMI), height, and death from prostate cancer in two large American Cancer Society cohorts. Men in the study were selected from the male participants in Cancer Prevention Study I (CPS-I; enrolled in 1959 and followed through 1972) and Cancer Prevention Study II (CPS-II; enrolled in 1982 and followed through 1996). After exclusions, 1,590 prostate cancer deaths remained among 381,638 men in CPS-I and 3,622 deaths among 434,630 men in CPS-II. Cox proportional hazards modeling was used to compute rate ratios (RR) and to adjust for confounders. Prostate cancer mortality rates were significantly higher among obese (BMI, > or =30) than nonobese (BMI, <25) men in both cohorts [adjusted RR, 1.27; 95% confidence interval (CI), 1.04-1.56 in CPS-I; RR, 1.21; 95% CI, 1.07-1.37 in CPS-II]. Prostate cancer mortality rates in the CPS-I cohort were lowest for the shortest men (RR, 0.80; 95% CI, 0.63-1.03 for men <65 inches versus 65-66 inches) and highest for the tallest men (RR, 1.39; 95% CI, 1.11-1.74 for men > or =73 inches tall versus 65-66 inches). Rates remained constant among men 65-72 inches tall. No association between height and prostate cancer mortality was observed in the CPS-II cohort (RR, 1.03; 95% CI, 0.82-1.29 for men > or =75 versus 65-66 inches). These results support the hypothesis that obesity increases risk of prostate cancer mortality. Decreased survival among obese men may be a likely explanation for this association.

Estrogen replacement therapy and ovarian cancer mortality in a large prospective study of US women.

CONTEXT: Postmenopausal estrogen use is associated with increased risk of endometrial and breast cancer, 2 hormone-related cancers. The effect of postmenopausal estrogen use on ovarian cancer is not established. OBJECTIVES: To examine the association between postmenopausal estrogen use and ovarian cancer mortality and to determine whether the association differs according to duration and recency of use. DESIGN AND SETTING: The American Cancer Society's Cancer Prevention Study II, a prospective US cohort study with mortality follow-up from 1982 to 1996. PARTICIPANTS: A total of 211 581 postmenopausal women who completed a baseline questionnaire in 1982 and had no history of cancer, hysterectomy, or ovarian surgery at enrollment. MAIN OUTCOME MEASURE: Ovarian cancer mortality, compared among never users, users at baseline, and former users as well as by total years of use of estrogen replacement therapy (ERT). RESULTS: A total of 944 ovarian cancer deaths were recorded in 14 years of follow-up. Women who were using ERT at baseline had higher death rates from ovarian cancer than never users (rate ratio [RR], 1.51; 95% confidence interval [CI], 1.16-1.96). Risk was slightly but not significantly increased among former estrogen users (RR, 1.16; 95% CI, 0.99-1.37). Duration of use was associated with increased risk in both baseline and former users. Baseline users with 10 or more years of use had an RR of 2.20 (95% CI, 1.53-3.17), while former users with 10 or more years of use had an RR of 1.59 (95% CI, 1.13-2.25). Annual age-adjusted ovarian cancer death rates per 100 000 women were 64.4 for baseline users with 10 or more years of use, 38.3 for former users with 10 or more years of use, and 26.4 for never users. Among former users with 10 or more years of use, risk decreased with time since last use reported at study entry (RR for last use <15 years ago, 2.05; 95% CI, 1.29-3.25; RR for last use >/=15 years ago, 1.31; 95% CI, 0.79-2.17). CONCLUSIONS: In this population, postmenopausal estrogen use for 10 or more years was associated with increased risk of ovarian cancer mortality that persisted up to 29 years after cessation of use.

Tubal sterilization and risk of breast cancer mortality in US women.

OBJECTIVE: To investigate the hypothesis that tubal sterilization is associated with a reduced risk of breast cancer. METHODS: We examined this hypothesis in a large prospective study of US adults. After 14 years of mortality follow-up, 3837 deaths from breast cancer were observed in a cohort of 619,199 women who were cancer-free at study entry in 1982. RESULTS: Cox proportional hazards models (adjusted for multiple breast cancer risk factors) showed a significant inverse association between tubal sterilization and breast cancer mortality (adjusted rate ratio (RR) = 0.82, 95% confidence interval (CI) 0.70-0.96). Women who were sterilized before age 35 had a lower risk (adjusted RR = 0.69, 95% CI 0.53-0.88) than women who were sterilized at 35 years of age or older (adjusted RR = 0.92, 95% CI 0.75-1.13). Also, sterilizations performed before 1975 resulted in a lower risk (RR = 0.75, 95% CI 0.62-0.91) than those performed during or after 1975 (RR = 0.98, 95% CI 0.74-1.29), possibly reflecting the likelihood of greater tissue damage with earlier procedures. CONCLUSIONS: These results suggest that tubal sterilization may lower subsequent risk of breast cancer, especially among women who are sterilized at a relatively young age. Additional studies are needed to confirm or refute these findings.

Vitamin C and vitamin E supplement use and colorectal cancer mortality in a large American Cancer Society cohort.

Some recent epidemiological studies have suggested that use of vitamin C or vitamin E supplements, both of which are important antioxidants, may substantially reduce the risk of colon or colorectal cancer. We examined the association between colorectal cancer mortality and use of individual vitamin C and E supplements in the American Cancer Society's Cancer Prevention Study II cohort. We used proportional hazards modeling to estimate rate ratios among 711,891 men and women in the United States who completed a self-administered questionnaire at study enrollment in 1982, had no history of cancer, and were followed for mortality through 1996. During the 14 years of follow-up, 4404 deaths from colorectal cancer occurred. After adjustment for multiple colorectal cancer risk factors, regular use of vitamin C or E supplements, even long-term use, was not associated with colorectal cancer mortality. The combined-sex rate ratios were 0.89 [95% confidence interval (CI), 0.73-1.09] for 10 or more years of vitamin C use and 1.08 (95% CI, 0.85-1.38) for 10 or more years of vitamin E use. In subgroup analyses, use of vitamin C supplements for 10 or more years was associated with decreased risk of colorectal cancer mortality before age 65 years (rate ratio = 0.48; 95% CI, 0.28-0.81) and decreased risk of rectal cancer mortality at any age (rate ratio = 0.40; 95% CI, 0.20-0.80). Our results do not support a substantial effect of vitamin C or E supplement use on overall colorectal cancer mortality.

Effect of body mass on the association between estrogen replacement therapy and mortality among elderly US women.

In observational studies, estrogen replacement therapy is associated with decreased cardiovascular disease rates and increased breast cancer rates. Recent evidence suggests that the impact of estrogen use on disease outcomes may vary by body mass. In a prospective study of 290,827 postmenopausal US women with no history of cancer or cardiovascular disease at enrollment in 1982, the authors examined the association between postmenopausal estrogen use and all-cause, coronary heart disease, stroke, all-cancer, and breast cancer death rates and whether these associations differed by body mass. After 12 years of follow-up, results from Cox proportional hazards models showed that all-cause death rates were lower among baseline estrogen users than never users (rate ratio (RR) = 0.82, 95% confidence interval (CI): 0.78, 0.87). The lowest relative risk was found for coronary heart disease (RR = 0.66, 95% CI: 0.58, 0.77). The inverse association between estrogen use and coronary heart disease mortality was strongest for thin women (body mass index <22 kg/m2) (RR = 0.49, p for interaction = 0.02). Breast cancer mortality did not increase with estrogen use overall, and no increased risk was observed for thin or heavy women. In this population, the reduction in coronary heart disease mortality among estrogen users was greatest for thinner women. Additional studies are needed to confirm or refute these results.

Alcohol consumption increases the risk of fatal breast cancer (United States).

OBJECTIVE: To investigate the hypothesis that alcohol consumption increases the risk of breast cancer mortality. METHODS: We examined breast cancer mortality in relation to self-reported alcohol consumption in women from the American Cancer Society Cancer Prevention Study (CPS)-II. After 14 years of follow-up, 1,442 eligible breast cancer deaths were observed among 242,010 women. Cox proportional hazards models were constructed for total alcohol consumption and for beer, wine, and liquor separately. RESULTS: Total alcohol consumption was associated with increased risk of fatal breast cancer among post- but not pre- or perimenopausal women. Even less than one drink/day was associated with up to a 30% increase in breast cancer mortality among postmenopausal women compared to non-drinkers (RR = 1.3, 95% CI: 1.1-1.6 for women drinking 0.26-<1 drink/day). When examined separately, consumption of beer, wine, and liquor each increased the risk of breast cancer among postmenopausal women. We found no evidence that alcohol consumption was more deleterious among women at high risk for breast cancer compared to average-risk women. CONCLUSION: This study adds to the evidence that postmenopausal women can reduce their risk of breast cancer by avoiding or minimizing their use of alcohol.

Multivitamin use and colon cancer mortality in the Cancer Prevention Study II cohort (United States).

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.

How does breast cancer mortality compare with that of other cancers and selected cardiovascular diseases at different ages in U.S. women?

Women tend to fear breast cancer and thus overestimate their risk of developing it, have less concern about developing heart disease, and do not know that lung cancer is the major cause of cancer death. Death certificate data, consolidated into a national database by the National Center for Health Statistics, were used to compare age-specific mortality due to selected cardiovascular diseases and cancers among women who died in 1997 in the United States. The outcomes examined included underlying cause of death categorized as all circulatory system disease, cerebrovascular disease, and heart disease, including coronary and noncoronary disease, and as all cancers combined plus cancer of the lung, breast, and colon/rectum. In 1997, 500,703 women in the United States died from diseases of the circulatory system, including 370,357 deaths from heart disease. Most deaths from heart disease were due to coronary heart disease, which exceeded mortality from cerebrovascular disease at all ages except under age 40. In 1997, 258,463 women in the United States died from cancer, and before age 55, breast cancer death rates exceeded lung and colorectal cancer death rates. Mortality due to total heart disease exceeded breast and lung cancer mortality among women at all ages, but before age 55, when absolute death rates are low, breast cancer death rates exceeded those for coronary heart disease. In conclusion, aside from mortality due to all cancers combined and circulatory system disease, only accidents, which were not included in this study, and total heart disease caused more deaths than breast cancer before age 55.