Lifestyle factors and Ki-ras mutations in colon cancer tumors.

Heterogeneity in colon tumors implies that environmental, lifestyle, or genetic factors influence the type of mutations seen in tumors. In this study we evaluate the association between previously identified risk factors for colon cancer and Kirsten-ras (Ki-ras) mutations in tumors. The presence of Ki-ras mutations in codons 12 and 13 were determined in a population-based case-control study of colon cancer. Participants were between 30 and 79 years of age at time of diagnosis and include both men and women. Questionnaire data were used to obtain information on lifestyle factors. Valid study data and Ki-ras mutational status were available from 1428 cases of colon cancer, data from 2410 controls were available for comparative purposes. Participants with Ki-ras mutations were more likely to have proximal rather than distal tumors. Cigarette smoking, use of aspirin and/or NSAIDs, use of vitamin/mineral supplements, and consumption of caffeine were associated with both Ki-ras+ and Ki-ras- tumors; the associations were not confounded by dietary intake or other lifestyle factors. Among men, but not among women, those with low levels of physical activity were more likely to have a tumor with a Ki-ras mutation than one without a Ki-ras mutation. However, among women, those with a larger BMI were more likely to have a Ki-ras mutation in their tumor. Given the limited information available on what causes Ki-ras mutations, the information generated from this study indicates that these factors previously associated with colon cancer work through other disease pathways.

Interplay between dietary inducers of GST and the GSTM-1 genotype in colon cancer.

The purpose of this study is to determine if cruciferous vegetables and coffee, two dietary inducers of glutatione-S-transferases, interact with GSTM-1 genotype to alter risk of colon cancer. Data were available on 1579 incident cases of adenocarcinoma of the colon and 1898 population-based controls. Intake of cruciferous vegetables, specific types of cruciferous vegetable, and coffee were not associated with colon cancer; GSTM-1 genotype did not modify these associations. However, age at diagnosis and cigarette smoking appeared to be important effect modifiers of the associations between GSTM-1, cruciferous vegetables and colon cancer. Among GSTM-1 null individuals, <55 years at diagnosis, we observed an inverse association between colon cancer and high levels of cruciferous vegetable intake relative to people who did not eat cruciferous vegetables (ORs 0.23 95% CI 0.10-0.54); broccoli was the cruciferous vegetable associated with the strongest inverse association (OR 0.30 95% CI 0.13-0.70). Among younger individuals who were GSTM-1 present (relative to those with GSTM-1 null), we observed an inverse association with colon cancer regardless of level of cruciferous vegetable intake (OR 0.74 95% CI 0.30-1.79 for no intake; OR 0.44 95% CI 0.21-0.92 for <4 servings/week; and OR 0. 44 95% CI 0.19-0.99 for >/=4 servings/week). These associations were further modified by cigarette smoking. People <65 years of age who smoked had a greater reduction in risk of colon cancer from consumption of cruciferous vegetables than non-smokers at the same age. In summary, although cruciferous vegetables do not appear to modify colon cancer risk in the total population, there are subgroups of the population for whom these vegetables may be important. These subgroups are defined mostly by age and smoking status.

Calcium, vitamin D, sunshine exposure, dairy products and colon cancer risk (United States).

OBJECTIVE: Epidemiologic studies on calcium, vitamin D and colon cancer are inconsistent, whereas experimental studies more regularly show a protective effect. To evaluate potential sources of inconsistencies, data from a large case-control study were analyzed, stratifying on potential effect modifiers. METHODS: Data were collected by certified interviewers in Northern California, Utah and Minnesota. Analyses included 1993 incident colon cancer cases and 2410 population-based controls. Multivariate logistic regression models included age, sex, BMI, family history, physical activity, intake of energy, dietary fiber, aspirin and NSAIDs. RESULTS: Dietary calcium was inversely associated with colon cancer risk in men (OR highest vs lowest quintile = 0.6, 95% CI = 0.5-0.9) and women (OR = 0.6, 95% CI = 0.4-0.9). No statistically significant associations were observed for dietary vitamin D or sunshine exposure. Consumption of total low-fat dairy products was associated with a statistically significantly decreased risk in men and women (ORs highest vs lowest category of intake = 0.8 and 0.7 respectively). Calcium supplement use was inversely associated with risk in both sexes (ORs use vs non-use = 0.8). Vitamin D supplements were inversely associated with risk in men (OR = 0.5) and women (OR = 0.6) but confidence limits included 1.0. CONCLUSIONS: These data provide additional support of an inverse association between high levels of calcium intake and colon cancer risk.

Carotenoids and colon cancer.

BACKGROUND: Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. OBJECTIVE: The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. DESIGN: Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). RESULTS: Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P < 0.01 for linear trend). The associations with other carotenoids were unremarkable. CONCLUSION: The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Lifestyle and colon cancer: an assessment of factors associated with risk.

Studies of the etiology of colon cancer indicate that it is strongly associated with diet and lifestyle factors. The authors use data from a population-based study conducted in northern California, Utah, and Minnesota in 1991-1995 to determine lifestyle patterns and their association with colon cancer. Data obtained from 1,993 cases and 2,410 controls were grouped by using factor analyses to describe various aspects of lifestyle patterns. The first five lifestyle patterns for both men and women loaded heavily on dietary variables and were labeled: "Western," "moderation," "calcium/low-fat dairy;" "meat and mutagens," and "nibblers, smoking, and coffee." Other important lifestyle patterns that emerged were labeled "body size," "medication and supplementation," "alcohol," and "physical activity." Among both men and women, the lifestyle characterized by high levels of physical activity was the most marked lifestyle associated with colon cancer (odds ratios = 0.42, 95% confidence interval: 0.32, 0.55 and odds ratio = 0.52, 95% confidence interval: 0.39, 0.69, for men and women, respectively) followed by medication and supplementation (odds ratio = 1.68, 95% confidence interval: 1.29, 2.18 and odds ratio = 1.63, 95% CI 1.23, 2.16, respectively). Other lifestyles that were associated with colon cancer were the Western lifestyle, the lifestyle characterized by large body size, and the one characterized by calcium and low-fat dairy. Different lifestyle patterns appear to have age- and tumor site-specific associations.

Vitamin E and colon cancer: is there an association?

The role of vitamin E in the etiology and prevention of colon cancer is not clear. It is possible that various forms of vitamin E may act differently in colon tissue and may be effective chemopreventive agents. Previous reports of vitamin E and colon cancer have focused on alpha-tocopherol and have not considered other dietary forms of vitamin E. Data from a study of 1,993 cases and 2,410 controls were used to evaluate the associations between the four most common forms of dietary vitamin E and supplemental vitamin E and colon cancer. After adjusting for other health and life-style factors, we did not observe a statistically significant association between dietary tocopherols and colon cancer. There were, however, suggestions of an inverse association between total alpha-tocopherol equivalents and colon cancer among women diagnosed with colon cancer before the median age of the control population, 67 years [odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.36-1.22] and a direct association between gamma-tocopherol and colon cancer among these women (OR = 1.44, 95% CI = 0.92-1.93). Women diagnosed with colon cancer when > or = 67 years of age appeared to have some protection from use of vitamin E supplements (OR = 0.80, 95% CI = 0.56-1.15). These data offer only limited support for a protective effect of vitamin E and colon cancer after adjustment for other health and life-style factors.

Dietary fats and colon cancer: assessment of risk associated with specific fatty acids.

There are many biological mechanisms whereby dietary fat and specific dietary fatty acids may alter risk of colon cancer in addition to their contribution to total energy intake. To evaluate these potential associations, we used detailed dietary intake data collected in a population-based study of 1,993 incident colon cancer cases and 2,410 controls conducted in 3 areas of the United States. The most commonly consumed fatty acid in the study population was oleic acid. One-third of dietary fats consumed came from additions to other foods at the table or from the preparation of other foods. After adjusting for total energy intake, physical activity and body size, neither total dietary fat nor specific fatty acids was associated with risk of colon cancer. However, among older women, fats from food preparation were associated with increased risk of colon cancer (OR 1.84, 95% CI 1.20-2.80), while fats from foods themselves or from additions to other foods were not. While dietary fats were not associated with colon cancer risk in the total population, subgroups of the population appeared to be at slightly greater risk if they consumed a high-fat diet. Women who consumed a diet high in mono-unsaturated fatty acids (MFAs) and poly-unsaturated fatty acids (PFAs) and who had a family history of colorectal cancer were at greater risk of colon cancer than those with similar intakes but without a family history of colorectal cancer. Similar associations with family history were noted among men diagnosed at younger ages for MFA, linolenic acid and 20-carbon PFA.

Plant foods and colon cancer: an assessment of specific foods and their related nutrients (United States).

Plant foods have been associated inversely with colon cancer. Since a major focus of this study was to identify components of plant foods which may account for their association with colon cancer, nutrients which are commonly found in plant foods also were evaluated. A population-based case-control study was conducted in Northern California, Utah, and the 'Twin Cities' area of Minnesota (United States). Complete data were available from interviewer-administered questionnaires on 1,993 cases and 2,410 controls. Higher intakes of vegetables (for highest relative to lowest quintile of intake) were associated inversely with colon cancer risk: the odds ratio (OR) was 0.7 for both men (95 percent [CI] confidence interval = 0.5-0.9) and women (CI = 0.5-1.0). Associations were stronger among those with proximal tumors. Total fruit intake was not associated with colon cancer risk although, among men, higher levels of whole grain intake were associated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men); high intakes of refined grains were associated with an increased risk (OR = 1.5, CI = 1.1-2.1). Dietary fiber intake was associated with a decreased risk of colon cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI = 0.4-1.2) for older women; OR = 0.6 (CI = 0.4-1.0) for men with proximal tumors; OR = 0.5 (CI = 0.3-0.9) for women with proximal tumors. Other nutrients, for which plant foods were the major contributor--such as vitamin B6, thiamin, and niacin (women only)--also were associated inversely with colon cancer. Neither beta-carotene nor vitamin C was protective for colon cancer. Adjustment of plant foods for nutrients found in plant foods or for supplement use did not appreciably alter the observed associations between plant foods and colon cancer.

Dietary antioxidants and plasma lipids: the CARDIA Study.

OBJECTIVE: To determine if dietary antioxidants play a role in preventing coronary heart disease (CHD) by having an impact on lipid levels. METHODS: Data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to assess the associations of reported intake of vitamins A, C, E and beta carotene, and their use in supplements, with lipid levels in a black and white, healthy adult (18 to 30 years of age at the baseline examination) population. RESULTS: After adjusting for age, education level, physical activity, body size, alcohol consumption and caloric intake, vitamin A, beta carotene, and vitamin C (white women) intake were directly associated with HDL-cholesterol levels among women who smoked cigarettes, with the strongest associations being observed for white women. Black men who took supplements of vitamins A and C and did not smoke cigarettes had significantly higher HDL-cholesterol levels compared to those in the lowest levels of dietary intake. Although vitamin E was associated with higher levels of HDL-cholesterol, the association was only of borderline significance among white men who smoked cigarettes (p = 0.06). We did not observe any consistent associations between antioxidants and other plasma lipids, including total cholesterol, LDL-cholesterol, or triglycerides. CONCLUSIONS: We conclude that dietary antioxidants are associated with HDL-cholesterol levels in some subsets of the population, although these associations may be operating in conjunction with other lifestyle behaviors.

Smoking, alcohol, coffee, tea, caffeine, and theobromine: risk of prostate cancer in Utah (United States).

Data from a population-based study of newly diagnosed cases of prostate cancer (n = 362) and age-matched controls (n = 685) conducted in Utah (United States) between 1983 and 1986 were used to determine if cigarette smoking, alcohol, coffee, tea, caffeine, and theobromine were associated with prostate cancer risk. These factors were examined since their use differs in the Utah population, which is comprised predominantly of members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormon), from most other populations. Pack-years of cigarettes smoked, alcohol intake, and consumption of alcohol, coffee, tea, and caffeine were not associated with prostate cancer risk. Compared with men with very low levels of theobromine intake, older men consuming 11 to 20 and over 20 mg of theobromine per day were at increased risk of prostate cancer (odds ratio [OR] for all tumors = 2.06, 95 percent confidence interval [CI] = 1.33-3.20, and OR = 1.47, CI = 0.99-2.19, respectively; OR for aggressive tumors = 1.90, CI = 0.90-3.97, and OR = 1.74, CI = 0.91-3.32, respectively). We present biological mechanisms for a possible association between prostate cancer and theobromine. This finding needs further exploration in studies with a wider range of theobromine exposures and more men with aggressive tumors.

Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors.

A population-based case-control study in Utah of 358 cases diagnosed with prostate cancer between 1984 and 1985, and 679 controls categorically matched by age and county of residence, were interviewed to investigate the association between dietary intake of energy (kcal), fat, protein, vitamin A, beta-carotene, vitamin C, zinc, cadmium, selenium, and prostate cancer. Dietary data were ascertained using a quantitative food-frequency questionnaire. Data were analyzed separately by age (45-67, 68-74) and by tumor aggressiveness. The most significant associations were seen for older males and aggressive tumors. Dietary fat was the strongest risk factor for these males, with an odds ratio (OR) of 2.9 (95 percent confidence interval [CI] 1.0-8.4) for total fat; OR = 2.2 (CI = 0.7-6.6) for saturated fat; OR = 3.6 (CI = 1.3-9.7) for monounsaturated fat; and OR = 2.7 (CI = 1.1-6.8) for polyunsaturated fat. Protein and carbohydrates had positive but nonsignificant associations. Energy intake had an OR of 2.5 (CI = 1.0-6.5). In these older men, no effects were seen for dietary cholesterol, body mass, or physical activity. There was little association between prostate cancer and dietary intake of zinc, cadmium, selenium, vitamin C, and beta-carotene. Total vitamin A had a slight positive association with all prostate cancer (OR = 1.6, CI = 0.9-2.4), but not with aggressive tumors. No associations were found in younger males, with the exception of physical activity which showed active males to be at an increased but nonsignificant risk for aggressive tumors (OR = 2.0, CI = 0.8-5.2) and beta-carotene which showed a nonsignificant protective effect (OR = 0.6, CI = 0.3-1.6). The findings suggest that dietary intake, especially fats, may increase risk of aggressive prostate tumors in older males.

Tobacco, alcohol, coffee, and caffeine as risk factors for colon cancer in a low-risk population.

We used data from a population-based case-control study to examine how use of tobacco products and consumption of alcohol, coffee, and caffeine relate to colon cancer in Utah. We hypothesized that low use of these substances is one factor contributing to the low colon cancer incidence in Utah and could help explain the low risk associated for colon cancer with being a member of the Church of Jesus Christ of Latter-day Saints. In females, we observed little or no increase in risk of colon cancer from smoking cigarettes or from consumption of alcohol, caffeine, or coffee. Males who used pipes, however, experienced an increased risk for colon cancer (OR = 4.1, 95% CI = 1.3-12.3). Risk for colon cancer associated with alcohol use was greatly attenuated after adjusting for caffeine and pipe use in males; males who consumed higher levels of caffeine during the two to three years prior to the interview were at higher risk than males who consumed low levels of caffeine (OR = 2.0, 95% CI = 1.0-4.2); similar associations were observed for coffee consumption. Nonuse of these substances could explain the low colon cancer incidence rates observed in members of the Church of Jesus Christ of Latter-day Saints and Utah males.

Dietary vitamins A, C, and E and selenium as risk factors for cervical cancer.

The relation between cervical cancer and dietary intake of vitamins A, C, and E, beta-carotene, and selenium was examined in a population-based case-control study in Utah. Cervical cancer cases (n = 266) and population-based controls (n = 408) were interviewed between 1984 and 1987. Protective effects were observed for vitamins A, C, and E and beta-carotene but were attenuated by age, level of education, and lifetime cigarette use. Associated risk (comparing highest with lowest quartiles of intake) went from 0.53 (crude) to 0.71 (adjusted) for vitamin A; from 0.55 (crude) to 0.82 (adjusted) for beta-carotene; from 0.45 (crude) to 0.55 (adjusted) for vitamin C; from 0.58 (crude) to 0.60 (adjusted) for vitamin E; and from 0.95 (crude) to 0.70 (adjusted) for selenium. Adjustment for number of sex partners and church attendance, factors significantly related to cervical cancer risk, only slightly attenuated these adjusted risk estimates.

Smoking and bladder cancer. The modifying effect of cigarettes on other factors.

A population-based, incidence case-control study was used to assess the effect of cigarette smoking on other risk factors for the development of bladder cancer. White men (n = 332) between the ages of 21 and 84 with bladder cancer were compared with 686 population-based controls. Cigarette smokers were classified by current smoking status as well as by amount, duration, inhalation patterns, age at first having smoked, and years since having stopped smoking. These variables were associated with a change in the risk for bladder cancer. The population-attributable risk associated with cigarette smoking was 48.5%. Risks from the use of other tobacco products such as cigars, pipes, snuff, and chewing tobacco, and from caffeinated coffee, tea, and alcoholic beverages were evaluated in light of cigarette smoking status. Cigarette smoking was shown to be both a confounder and an effect modifier. Risk estimates for bladder cancer associated with caffeinated coffee and alcoholic beverages were decreased after controlling for the effects of cigarette smoking. However, an increased risk of developing bladder cancer from cigar smoking (Odds ratio [OR] = 2.46) and tea drinking (OR = 3.14) was only seen in men who never smoked cigarettes. An increased but not significant risk was also seen for pipe, snuff, and chewing tobacco use in noncigarette smokers. The population-attributable risk from cigars and tea in the population of white men who had never smoked was 6.3% and 18.9%, respectively. Our results suggest that cigarette smoking may obscure other risk factors unless those who never smoked are separately studied.