Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance

BACKGROUND: Experimental and epidemiologic investigations suggest that alpha-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and beta-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received beta-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of beta-carotene and vitamin A. PURPOSE: We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. METHODS: A total of 29,133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), alpha-tocopherol and beta-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of alpha-tocopherol and beta-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided statistical tests. RESULTS: No overall effect was observed for lung cancer from alpha-tocopherol supplementation (relative risk [RR] = 0.99; 95% confidence interval [CI] = 0.87-1.13; P = .86, logrank test). beta-Carotene supplementation was associated with increased lung cancer risk (RR = 1.16; 95% CI = 1.02-1.33; P = .02, logrank test). The beta-carotene effect appeared stronger, but not substantially different, in participants who smoked at least 20 cigarettes daily (RR = 1.25; 95% CI = 1.07-1.46) compared with those who smoked five to 19 cigarettes daily (RR = 0.97; 95% CI = 0.76-1.23) and in those with a higher alcohol intake (> or = 11 g of ethanol/day [just under one drink per day]; RR = 1.35; 95% CI = 1.01-1.81) compared with those with a lower intake (RR = 1.03; 95% CI = 0.85-1.24). CONCLUSIONS: Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke. beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers, and this effect may be associated with heavier smoking and higher alcohol intake. IMPLICATIONS: While the most direct way to reduce lung cancer risk is not to smoke tobacco, smokers should avoid high-dose beta-carotene supplementation.     

Intramural aortic dissection

OBJECTIVE: To investigate possible associations between tobacco smoking and alcohol consumption and the risk of adult glioma. DESIGN: This was a population based, case-control study. Relative risks (RR) were estimated using logistic regression analysis. SETTING: Melbourne, Australia. PARTICIPANTS: These comprised 416 case subjects (166 women, 250 men), 66% of those eligible; and 422 control subjects (170 women, 252 men), 43.5% of those potentially eligible. RESULTS: There was no increase in risk of glioma with having ever smoked tobacco (RR 1.29, 95% CI 0.95, 1.75) for all subjects, adjusted for age, a reference date, and gender. There was a slight increase in risk for men (RR 1.64, 95% CI 1.1, 2.45), but not for women (RR 0.99, 95% CI 0.62, 1.62). For men, there was no increase in risk with increasing pack-years of cigarette smoking, but the risk was significantly increased in subjects who had smoked for less than 10 years. There was no increase in risk associated with having ever drunk alcohol for all subjects (RR 0.96, 95% CI 0.67, 1.37), women (RR 0.69, 95% CI 0.4, 1.15) or men (RR 1.40, 95% CI 0.81, 2.43). CONCLUSIONS: This study does not support an association between either tobacco smoking or alcohol consumption and glioma. The pattern of risk associated with tobacco smoking in men appears inconsistent with a causal role, and may be due to chance, response bias, or uncontrolled confounding.     

Protein kinases A and C phosphorylate purified Ca2+-ATPase from rat cortex, cerebellum and hippocampus

Previous knowledge on risk factors for oral, pharyngeal, laryngeal, and esophageal cancer has been based mainly on case-control studies. In the present study, the impact of alcohol consumption, tobacco smoking, and dietary factors on upper aerogastric tract cancer risk was studied in a cohort of 10,960 Norwegian men followed from 1968 through 1992, in which period a total of 71 upper aerogastric tract cancers occurred. The relative risk (RR) of cancer was 3.9 (95 percent confidence interval [CI] = 2.1-7.1) for the highest consumption group of alcohol and 4.7 (CI = 1.7-13.2) for the highest smoking level, compared with the respective reference groups. Among the dietary items, high consumption of oranges was associated with reduced cancer risk (RR = 0.5, CI = 0.3-1.0), as was high consumption of bread (RR = 0.2, CI = 0.1-0.5). Frequent consumption of beef and bacon increased relative cancer risk bordering on significance. The present results are largely in accordance with previous studies. The decreased risk associated with a high intake of bread deserves further investigation.     

Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-->T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-->carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.     

Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives

We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.     

Smoking patterns and cancer of the oral cavity and pharynx: a case-control study in Uruguay

A case-control study of cancer of the oral cavity and pharynx was conducted in Uruguay, between 1992 and 1996. 425 patients microscopically diagnosed with squamous cell carcinoma of the oral cavity and pharynx were frequently matched on age, residence, and urban/rural status with 427 hospitalised controls. The study was restricted to males. Smokers of black tobacco cigarettes were associated with an increased risk of 12.1 (95% confidence interval (CI) 7.6-19.4), when compared with non-smokers after fitting a model which included the matching variables, birthplace, education, and total alcohol consumption. Lifelong smokers of hand-rolled cigarettes displayed an odds ratio (OR) of 8.7 (95% CI 5.6-13.4), compared with non-smokers. When smokers were excluded from the calculations, the OR for smokers of black tobacco cigarettes was 3.0 (95% CI 2.0-4.6), compared with smokers of blond tobacco cigarettes, after controlling for the same variables mentioned above, plus pack-years, years since stopping, and filter use. Hand-rolling appears to be less important than smoking black tobacco in this study (OR 1.6, 95% CI 0.9-2.5). Thus, smoking black tobacco cigarettes appears to be an important habit in oral and pharyngeal carcinogenesis.     

Increased cancer mortality following a history of nonmelanoma skin cancer

CONTEXT: Cancer registries have reported an increased incidence of melanoma and certain noncutaneous cancers following nonmelanoma skin cancer (NMSC). Whether these findings were attributable to intensified surveillance, shared risk factors, or increased cancer susceptibility remains unclear. OBJECTIVE: To determine whether a history of NMSC predicts cancer mortality. DESIGN: Prospective cohort with 12-year mortality follow-up adjusted for multiple risk factors. SETTING: Cancer Prevention Study II, United States and Puerto Rico. PARTICIPANTS: Nearly 1.1 million adult volunteers who completed a baseline questionnaire in 1982. MAIN OUTCOME MEASURE: Deaths due to all cancers and common cancers. RESULTS: After adjusting for age, race, education, smoking, obesity, alcohol use, and other conventional risk factors, a baseline history of NMSC was associated with increased total cancer mortality (men's relative risk [RR], 1.30; 95% confidence interval [CI], 1.23-1.36; women's RR, 1.26; 95% CI, 1.17-1.35). Exclusion of deaths due to melanoma reduced these RRs only slightly. Mortality was increased for the following cancers: melanoma (RR, 3.36 in men, 3.52 in women); pharynx (RR, 2.77 in men, 2.81 in women); lung (RR, 1.37 in men, 1.46 in women); non-Hodgkin lymphoma (RR, 1.32 in men, 1.50 in women); in men only, salivary glands (RR, 2.96), prostate (RR, 1.28), testis (RR, 12.7), urinary bladder (RR, 1.41), and leukemia (RR, 1.37); and in women only, breast (RR, 1.34). All-cause mortality was slightly increased (adjusted men's RR, 1.03 [95% CI, 1.00-1.06]; women's RR, 1.04 [95% CI, 1.00-1.09]). CONCLUSIONS: Persons with a history of NMSC are at increased risk of cancer mortality. Although the biological mechanisms are unknown, a history of NMSC should increase the clinician's alertness for certain noncutaneous cancers as well as melanoma.     

Breast cancer risk and alcohol consumption: results from a large case-control study

BACKGROUND: Alcohol use is associated with breast cancer in many epidemiological studies. Most, however, have measured risk from recent consumption patterns, and only a few include analyses for duration of drinking or age that a woman started to drink. The authors studied the effect of these variables, as well as of recent alcohol consumption patterns, on breast cancer risk. METHODS: Data from a large case-control study conducted in Long Island, New York from 1 January 1984 to 31 December 1986 were used. A total of 1214 women aged 20-79 years with incident breast cancer were interviewed. A control was selected for each case from driver's license files, and matched on age and county of residence. Alcohol consumption was measured as: ever versus never, grams of alcohol per day, age started drinking, and total years drinking. RESULTS: After adjustment for breast cancer risk factors, the odds ratio for ever versus never drinking was 1.40 (95% confidence interval [CI] 1.09-1.79); odds ratios for > 0-5 and > or = 5 grams of alcohol use per day, as compared to nondrinkers, were 1.29 (95% CI: 1.00-1.65) and 1.46 (95% CI: 1.13-1.89), respectively. Age when drinking began was not related to breast cancer risk, but the greater the total years of drinking, up to 40 years (odds ratio 1.48, 95% CI: 1.13-1.93), the greater the risk. However, when grams per day and duration of drinking were simultaneously included in the multivariate model, duration was not important as a risk factor. This suggests that intensity of drinking may be the important factor for breast cancer risk. After covariate adjustment, risk from alcohol intake did not differ between pre- and postmenopausal women.     

Alcohol consumption and risk of breast cancer: the Framingham Study revisited

Although many studies report that moderate-to-heavy alcohol intake increases breast cancer risk, the effect of light alcohol consumption remains controversial, and a consistent pattern of association with different types of alcoholic beverages is not evident. The authors examined the relation of average alcohol consumption and of different beverages to the risk of breast cancer in the Framingham Study (Framingham, Massachusetts). Of 2,764 women followed more than 40 years in the Original Cohort from 1948 to 1993 and 2,284 followed up to 24 years in the Offspring Cohort from 1971 to 1993, 221 and 66 incident breast cancer cases occurred, respectively. Breast cancer incidence decreased from 3.60 per 1,000 person-years to 2.47, 2.30, and 2.33 in increasing categories of average alcohol consumption (none, < 5.0, 5.0-< 15.0, and > or = 15.0 g/day) among the Original Cohort and from 3.07 to 1.26, 1.24, and 2.22, respectively, among the Offspring Cohort. With the two cohorts combined, multivariate-adjusted rate ratios of breast cancer in each increased category of alcohol consumption were 1.0 (nondrinkers), 0.8 (95% confidence interval (CI) 0.6-1.1), 0.7 (95% CI 0.5-1.1), and 0.7 (95% CI 0.5-1.1), respectively. Breast cancer was not associated with wine, beer, or spirits consumption when assessed separately. The findings suggest that the light consumption of alcohol or any type of alcoholic beverage is not associated with increased breast cancer risk.     

Intake of beer, wine, and spirits and risk of stroke : the copenhagen city heart study

BACKGROUND and PURPOSE: Alcohol consumption has been associated with a protective effect on risk of ischemic stroke. There may, however, be differences in the effect of beer, wine, and spirits due to properties other than ethanol, a topic that has gained only little attention in stroke research. METHODS: Our analysis was a prospective cohort study of 13 329 eligible men and women, aged 45 to 84 years, participating in the Copenhagen City Heart Study. Information on alcohol habits and a number of socioeconomic and health-related factors was obtained at baseline. During 16 years of follow-up, 833 first-ever strokes occurred. Data were analyzed by means of multiple Poisson regression. RESULTS: We found indications of a U-shaped relation between intake of alcohol and risk of stroke. In analyses adjusted for age, sex, and smoking, intake of wine on a monthly, weekly, or daily basis was associated with a lower risk of stroke compared with no wine intake (monthly: relative risk [RR], 0. 83; 95% CI, 0.69 to 0.98; weekly: RR, 0.59; 95% CI, 0.45 to 0.77; daily: RR, 0.70; 95% CI, 0.46 to 1.00). This effect of wine intake remained after complete adjustment for confounding variables (monthly: RR, 0.84; 95% CI, 0.70 to 1.02; weekly: RR, 0.66; 95% CI, 0.50 to 0.88; daily: RR, 0.68; 95% CI, 0.45 to 1.02). There was no association between intake of beer or spirits on risk of stroke. CONCLUSIONS: The differences in the effects of beer, wine, and spirits on the risk of stroke suggest that compounds in the wine in addition to ethanol are responsible for the protective effect on risk of stroke.     

Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries

PURPOSE: To compare the risk for fatal myocardial infarction (MI) after adjuvant radiotherapy (RT) for left-sided breast cancer with the risk for MI after adjuvant RT for right-sided breast cancer. METHODS: We studied women with local- and regional-stage breast cancer diagnosed from 1973 to 1992 from the Surveillance, Epidemiology, and End-Results (SEER) cancer registries. We performed life-table analysis, the log-rank test, and Cox proportional hazards regression to compare the time to fatal MI from diagnosis between left-sided and right-sided cases, censoring deaths from other causes. RESULTS: Among irradiated patients, the relative risk (RR) for fatal MI in women with left-sided breast cancer was 1.17 (95% confidence interval [CI], 1.01 to 1.36), controlling for age, compared with those with right-sided breast cancer. The RR for fatal MI among left-sided cases was increased for those under the age of 60 years (RR = 1.98; 95% CI, 1.31 to 2.97) compared with right-sided cases, but not at age 60 years or older. Among women with irradiated regional-stage cancer who were younger than 60 years of age, the risk was significantly increased (RR = 2.24; 95% CI, 1.38 to 3.64) for those with left-sided compared with right-sided breast cancer, but not among patients aged 60 years or older. Among irradiated local-stage cases, the risk for those with left-sided breast cancer was not significantly elevated in either age category. Analysis of 5-year conditional survival cohorts showed an increased risk for irradiated left-sided cases among women younger than 60 years of age in the 10- to 15-year conditional survival cohort (RR = 5.28; 95% CI, 1.82 to 15.3). CONCLUSION: Adjuvant RT for left-sided breast cancer diagnosed in women younger than 60 years of age is associated with a higher risk for fatal MI 10 to 15 years later compared with adjuvant RT for right-sided cases.     

Sale of cigarettes to school children aged 14 and 15 years in New Zealand

AIMS: To determine the sources of cigarettes and extent of illegal sales to 14 and 15 year old children, and to examine associated risk factors in order to more effectively reduce tobacco access to children. METHOD: Nationwide cross sectional survey of fourth form school children in New Zealand by means of an anonymous self administered questionnaire. RESULTS: Questionnaires from 14,097 fourteen and fifteen years olds were analysed, with over one third smokers. Twenty four percent of the whole group (3432) had bought cigarettes in the last year. Of smokers, 59.9% bought their own, with the great majority (68.9%) from dairies, particularly females. Ninety five percent said it was "easy" or "very easy" to buy cigarettes, and this was a major risk factor for this behaviour (relative risk (RR) = 2.01, 95% confidence interval (CI) 1.74, 2.32, RR = 2.54, CI 2.28, 2.83, respectively). Only 24.6% children had ever been refused cigarettes because of age and all points of sale were comparable in this respect. Heavy smokers and males were more likely to have been refused. While refusal was associated with a fourfold increase in the perception that it was difficult to buy cigarettes, there was only a minimal reduction in the risk of children buying their own cigarettes (RR = 0.95, CI 0.91, 1.00). CONCLUSION: We have shown that the illegal sale of cigarettes to children is unacceptably easy and accurately perceived as such by children who smoke. The active enforcement of existing or future legislation is essential, with prosecution of offending retailers, if we are to make any progress to reduce the high prevalence of smoking in New Zealand children.     

Dose-dependent induction of both pepsinogen-altered pyloric glands and adenocarcinomas in the glandular stomach of C3H mice treated with N-methyl-N-nitrosourea

BACKGROUND: Cigarette smoking has been shown to increase oxidative DNA damage in human sperm cells. Assessment of the role of cigarette smoking in the etiology of childhood cancer has focused primarily on the effect of maternal smoking. Similar studies in relation to paternal smoking, however, have been inconclusive. Few studies have evaluated the effect of paternal smoking in the preconception period, and most of these could not disentangle the effects of paternal from maternal smoking. PURPOSE: We investigated the relationship of paternal smoking, particularly in the preconception period, with childhood cancer among offspring of the nonsmoking mothers. METHODS: We conducted a population-based, case-control study in Shanghai, People's Republic of China, where the prevalence of smoking is high among men but extremely low among women. The study included 642 childhood cancer case patients (<15 years of age) and their individually matched control subjects. Information concerning parental smoking, alcohol drinking, and other exposures of the index child was obtained by direct interview of both parents of the study subjects. Odds ratios (ORs), derived from conditional logistic regression models, were used to measure the association between paternal smoking and risk of childhood cancers. RESULTS AND CONCLUSIONS: Paternal preconception smoking was related to a significantly elevated risk of childhood cancers, particularly acute leukemia and lymphoma. The risks rose with increasing pack-years of paternal preconception smoking for acute lymphocytic leukemia (ALL) (P for trend = .01), lymphoma (P for trend = .07), and total cancer (P for trend = .006). Compared with children whose fathers had never smoked cigarettes, children whose fathers smoked more than five pack-years prior to their conception had adjusted ORs of 3.8 (95% confidence interval [CI] = 1.3-12.3) for ALL, 4.5 (95% CI = 1.2-16.8) for lymphoma, 2.7 (95% CI = 0.8-9.9) for brain tumors, and 1.7 (95% CI = 1.2-2.5) for all cancers combined. Statistically significant increased risks of cancer were restricted to children under the age of 5 years at diagnosis or those whose fathers had smoked during all of the 5 years prior to conception. IMPLICATIONS: Further studies are needed to confirm the association of paternal smoking with increased risk of cancer in offspring, to clarify the pattern of risks in relation to the timing of cigarette smoking, and to elucidate the biologic mechanism involved in predisposing the offspring to cancer. For example, it may be that paternal smoking induces prezygotic genetic damage that, in turn, acts as the predisposing factor.     

Alcohol, smoking, and cataracts: the Blue Mountains Eye Study

OBJECTIVE: To investigate the associations between alcohol consumption, tobacco smoking, and cataract. DESIGN: A population-based, cross-sectional study. SETTING: An urban community in the Blue Mountains, close to Sydney, Australia. PARTICIPANTS: Three thousand six hundred fifty-four people aged 49 to 97 years. The participation rate was 82%. MAIN OUTCOME MEASURES: Smoking history and details of current alcohol consumption were assessed by questionnaire. Lens photographs were taken and graded for presence and severity of cortical, nuclear, and posterior subcapsular cataracts. RESULTS: After adjusting for multiple potential confounders, people who had ever smoked cigarettes had a higher prevalence than nonsmokers of more severe nuclear (adjusted odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.6) and posterior subcapsular (adjusted OR, 1.5; 95% CI, 1.1-2.1) cataracts. The association between pipe smoking and nuclear cataract (adjusted OR, 3.1; 95% CI, 1.5-8.2) was stronger than the association with cigarette smoking. Alcohol consumption was associated with a reduced prevalence of cortical cataract: compared with people who did not drink, the adjusted OR for cortical cataract among people who drank at least 1 drink a day was 0.7 (95% CI, 0.6-0.9). Heavy alcohol consumption (> or =4 drinks a day) was associated with nuclear cataract in current smokers (adjusted OR compared with nondrinkers, 3.9; 95% CI, 0.9-16.6) but not in never smokers. CONCLUSIONS: Consistent with other studies, smoking was associated with a higher prevalence of nuclear and posterior subcapsular cataracts. The only adverse effect of alcohol was among smokers: people who smoked and drank heavily had an increased prevalence of nuclear cataract.     

A prospective study of dietary fiber types and symptomatic diverticular disease in men

To examine prospectively dietary fiber calculated from food composition values based on analytic techniques and specific dietary fiber types in relation to risk of diverticular disease, we analyzed data from a prospective cohort of 43,881 U.S. male health professionals 40-75 y of age at base line; subjects were free of diagnosed diverticular disease, colon or rectal polyps, ulcerative colitis and cancer. The insoluble component of fiber was inversely associated with risk of diverticular disease relative risk (RR) = 0. 63, 95% confidence interval (CI), 0.44-0.91, P for trend = 0.02, and this association was particularly strong for cellulose (RR = 0.52, 95% CI, 0.36-0.75, P for trend = 0.002). The association between diverticular disease and total dietary fiber intake calculated from the AOACstandards method was not appreciably different from results using the Southgate or Englyst method [for AOAC method, RR = 0.60, 95% CI, 0.41-0.87; for Southgate method, RR = 0.61, 95% CI, 0.42-0. 88; for Englyst method, RR = 0.60, 95% CI, 0.42-0.87, for the highest quintiles]. Our findings provide evidence for the hypothesis that a diet high in dietary fiber decreases the risk of diverticular disease, and this result was not sensitive to the use of different analytic techniques to define dietary fiber. Our findings suggest that the insoluble component of fiber was significantly associated with a decreased risk of diverticular disease, and this inverse association was particularly strong for cellulose.     

Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men

To examine the associations between intakes of calcium, Vitamin D, and dairy foods and the risk of colon cancer, the authors analyzed data from a prospective study of 47,935 US male professionals, 40-75 years of age and free of cancer in 1986. Within this cohort, 203 new cases of colon cancer were documented between 1986 and 1992. After adjusting for age and total energy intake, the authors found that the intake of calcium from foods and supplements was inversely associated with colon cancer risk (relative risk (RR) = 0.58, 95% confidence interval (CI) 0.39-087 between high and low intakes of calcium). However, after adjusting for confounding variables, they found that the trend was no longer statistically significant (p = 0.22), and the relative risk for the highest quintile group of intake was attenuated: 0.75 (95% CI 0.48-1.15). Similar results were observed for total vitamin D intake; the age- and energy-adjusted relative risk was 0.54% (95% CI 0/34-0/85) for the highest versus lowest quintile group, and this was attenuated in the multivariate model (RR = 0.66, 95% CI 0.42-1.05). The inverse association was weaker for dietary vitamin D (RR highest vs. lowest quintile = 0.88. 95% CI 0.54-1.42) and strongest for vitamin D arising from vitamin supplements (RR = 0.48, 95% CI 0.22-1.02). Thus, it is possible that other components of multivitamin use rather than vitamin D accounted for the reduction in risk. Consumption of milk and fermented dairy products was not significantly associated with the risk of colon cancer; individuals consuming two or more glasses of "whole" or skim milk per day had a relative risk of 1.09 (95% CI 0.69-1.72), compared with those who consumed "whole or skim milk less than once a month. These prospective data do not support the hypothesis that calcium intake is strongly protective against colon cancer risk, although a modest association cannot be excluded.     

Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men

BACKGROUND: The appropriateness of current cardiovascular disease (CVD) risk factor guidelines in women continues to be debated. OBJECTIVE: To present new data on the appropriateness of current CVD risk factor guidelines, for women and men, from long-term follow-up of a large population sample. METHODS: Cardiovascular disease risk factor status according to current clinical guidelines and long-term impact on mortality were determined in 8686 women and 10503 men aged 40 to 64 years at baseline from the Chicago Heart Association Detection Project in Industry; average follow-up was 22 years. RESULTS: At baseline, only 6.6% of women and 4.8% of men had desirable levels for all 3 major risk factors (cholesterol level, <5.20 mmol/L [<200 mg/dL]; systolic and diastolic blood pressure, <120 and <80 mm Hg, respectively; and nonsmoking). With control for age, race, and other risk factors, each major risk factor considered separately was associated with increased risk of death for women and men. In analyses of combinations of major risk factors, risk increased with number of risk factors. Relative risks (RRs) associated with any 2 or all 3 risk factors were similar: for coronary heart disease mortality in women, RR= 5.72 (95% confidence interval [CI], 2.35-13.93), and in men, RR = 5.51 (95% CI, 3.10-9.77); for CVD mortality in women, RR = 4.54 (95% CI, 2.33-8.84), and in men, RR = 4.12 (95% CI, 2.56-6.37); and for all-cause mortality in women, RR = 2.34 (95% CI, 1.73-3.15), and in men, RR = 3.20 (95% CI, 2.47-4.14). Absolute excess risks were high in women and men with any 2 or all 3 major risk factors. CONCLUSIONS: Combinations of major CVD risk factors place women and men at high relative, absolute, and absolute excess risk of coronary heart disease, CVD, and all-cause mortality. These findings support the value of (1) measurement of major CVD risk factors, especially in combination, for assessing long-term mortality risk and (2) current advice to match treatment intensity to the level of CVD risk in both women and men.     

Gamma-heavy chain disease associated with MALT lymphoma of the duodenum

BACKGROUND: Glutathione S-transferases (GSTs) are encoded by a superfamily of genes and play a role in the detoxification of potential carcinogens. In a nested case-control study, we investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1, and GSTP1) and susceptibility to breast cancer. METHODS: In 1989, a total of 32 898 individuals donated blood samples to a research specimen bank established in Washington County, MD. Genotypes of blood specimen DNA were determined for 110 of 115 women with incident cases of breast cancer diagnosed during the period from 1990 through 1995 and up to 113 of 115 control subjects. Associations between specific genotypes and the development of breast cancer were examined by use of logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The GSTM1 homozygous null genotype was associated with an increased risk of developing breast cancer (OR = 2.10; 95% CI = 1.22-3.64), principally due to an association with postmenopausal breast cancer (OR = 2.50; 95% CI = 1.34-4.65). For GSTP1, the data were suggestive of a trend of increasing risk with higher numbers of codon 105 valine alleles (compared with isoleucine alleles); a 1.97-fold increased risk of breast cancer (95% CI = 0.77-5.02) was associated with valine/valine homozygosity. The risk of breast cancer associated with the GSTT1 homozygous null genotype was 1.50 (95 % CI = 0.76-2.95). The risk of breast cancer increased as the number of putative high-risk genotypes increased (P for trend <.001) (OR = 3.77; 95% CI = 1.10-12.88 for a combined genotype of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity). CONCLUSIONS: Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to breast cancer.