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Background Ovarian cancer is the fifth most common cause of cancer death among women in the US, yet few modifiable risk factors have been established. Diets high in glycemic index (GI) and glycemic load (GL) have been linked to several cancers, but epidemiologic studies of ovarian cancer have yielded inconsistent results. Objective In this study, we aimed to examine associations between GI or GL and ovarian cancer. Methods We used prospective data from the Prostate, Lung, Colorectal, and Ovarian cohort. GI and GL were calculated from validated FFQs. Participants were women who were aged 60 to 74 y, did not have a history of cancer, and had both ovaries. Cox proportional hazard models were used to calculate HRs and 95% CIs for risk of ovarian cancer associated with quartiles of GI and GL. Analyses were performed separately for those who completed the dietary questionnaire at baseline (DQX) or later in the study (DHQ). Results From the DQX sample set, 181 cases were identified among 24,633 women with median follow-up of 12.1 y; there were 211 cases among 42,410 women in the DHQ set, with median follow-up of 8.9 y. After adjusting for age at dietary questionnaire completion, year of randomization, year of questionnaire, study center, and oral contraceptive use, the risk of ovarian cancer decreased by 43% (HR: 0.57; 95% CI: 0.37, 0.88) among those in the highest compared with those in the lowest quartile of GL (DQX). Those in the highest compared with those in the lowest quartile of GI (DHQ), had a 38% lower risk (HR: 0.62; 95% CI: 0.42, 1.00). Conclusions We observed lower risk of ovarian cancer associated with higher GI and GL. Results should be interpreted with caution as they may have been influenced by limitations including lack of variability in dietary intake. Additional studies are needed to better understand what is driving these associations.

Plant sterols or phytosterols are common components of plant foods, especially plant oils, seeds and nuts, cereals and legumes. The most common phytosterols are campesterol, beta-sitosterol and stigmasterol. Phytosterols have anticarcinogenic properties. Previous studies have suggested that populations with low breast cancer incidence often consume diets high in phytosterols. The present study evaluated whether consumption of a plant food-based diet, low in animal fat, may increase serum phytosterol levels in postmenopausal women. One hundred and four women volunteers were randomized to dietary intervention or control groups. The dietary intervention included intensive dietary counseling to replace animal products with plant-based foods. Subjects in the dietary intervention group participated twice a week for 18 wk in workshops about the preparation and consumption of a plant food-based diet. The absolute change in serum total phytosterol concentration was greater in the dietary intervention group than in the control group. The percent change tended to differ between groups (P = 0.06). However, only for beta-sitosterol did the absolute and percent changes within a group differ significantly between groups (P = 0.0017). The decrease in serum total cholesterol in the dietary intervention group (-14%) was greater than that in the control group (-4%; P = 0.0005). The results of this study show that circulating levels of phytosterols can be affected by dietary modification. These findings indicate that phytosterols, in particular beta-sitosterol, can be used as biomarkers of exposure in observational studies or as compliance indicators in dietary intervention studies of cancer prevention.

Although there is clear evidence that smoking is the primary risk factor for lung cancer, not all variation in disease risk is understood. There is some evidence that alcohol may contribute to risk. We examined lifetime and recent (12-24 mo previous) alcohol consumption in relation to risk of lung cancer in a case-control study in western New York. In addition we examined the alcohol dehydrogenase 3 (ADH 3 ) genotype in relation to lung cancer risk; ADH 3 is rate limiting in alcohol metabolism and has a functional polymorphism. We interviewed incident, primary, histologically confirmed lung cancer cases (n = 111) in two counties. Controls were randomly selected from among those residing in the counties, frequency-matched to cases for age and race (n = 1546). Lifetime and recent total alcohol and beverage-specific alcohol consumption as well as relevant confounders were assessed by interview. ADH 3 genotype was evaluated by a PCR-restriction fragment length polymorphism assay. Because of the small sample size, power was limited and Cl were wide. Residual confounding by smoking remains a concern. Although we found a significant trend for increased risk for beer consumption in the recent period (odds ratio 1.67, 95% Cl 0.96-2.92, P for trend = 0.05), chance cannot be ruled out as an explanation. We found no evidence of risk related to lifetime alcohol consumption nor evidence that alcohol dehydrogenase genotype modifies risk related to alcohol and lung cancer.

Intakes of specific nutrients and food groups have been shown previously to be related to ovarian cancer risk, but no studies, to our knowledge, have emphasized the effect of phytochemical intakes on this cancer. We conducted a case-control study of diet and ovarian cancer in western New York involving 124 primary, histologically confirmed ovarian cancer cases and 696 population-based controls, frequency matched to cases on age and county of residence. Diet was assessed with a detailed food-frequency questionnaire. Nutrient and phytochemical intakes were calculated from published food composition data. The odds ratios (OR) and 95% CI for risk of ovarian cancer with each nutrient, phytochemical and food group were estimated with unconditional logistic regression adjusting for age, education, total months menstruating, difficulty becoming pregnant, oral contraceptive use, menopausal status and energy intake. Compared with women in the lowest quintile of intake, reduced risks were observed for women in the highest quintile of intake of dietary fiber (OR 0.43, 95% CI, 0.20-0.94), total carotenoids (OR 0.33, 95% CI, 0.16-0.68), stigmasterol (OR 0.42, 95% CI, 0.20-0.87), total lignans (OR 0.43, 95% CI, 0.21-0.85), vegetables (OR 0.47, 95% CI, 0.23-0.97) and poultry (OR 0.45, 95% CI, 0.22-0.92). These results support a protective effect on ovarian cancer of phytoestrogen intakes, and our results support the hypothesis that a plant-based diet may be important in reducing risks of hormone-related neoplasms.

Glutathione-S-transferases catalyze the detoxication of carcinogen metabolites and reactive oxygen species (ROS) produced through a number of mechanisms. Glutathione-S-transferase (GST) M1 is polymorphic, and the null allele results in a lack of enzyme activity. Because there are indications that ROS may be involved in breast carcinogenesis, we sought to determine whether the GSTM1 null allele was associated with increased breast cancer, particularly among women with lower consumption of dietary sources of alpha-tocopherol, carotenoids and ascorbic acid. In a study of diet and cancer in western New York, women with primary, incident, histologically confirmed breast cancer (n = 740) and community controls (n = 810) were interviewed and an extensive food-frequency questionnaire administered. A subset of these women provided a blood specimen. DNA was extracted and genotyping performed for GSTM1. Data were available for 279 cases and 340 controls. The null allele did not increase breast cancer risk, regardless of menopausal status. There were also no differences in associations between the polymorphism and risk among lower and higher consumers of dietary sources of antioxidants or smokers and nonsmokers. These results indicate that GSTM1 genetic polymorphisms are not associated with breast cancer risk, even in an environment low in antioxidant defenses.

We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age-specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records.

The role of vegetable consumption in relation to breast cancer risk is controversial. Anticarcinogenic compounds may be present only in specific vegetables, thereby attenuating findings for total vegetable intake. Cruciferous vegetables contain precursors of isothiocyanates (ITCs), which may be chemopreventive through potent inhibition of phase I, and induction of phase II enzymes, such as glutathione S-transferases (GSTs). We investigated associations between consumption of cruciferous vegetables, sources of ITCs, and breast cancer risk, and potential modification of relations by GSTM1 and GSTT1 genotypes. Cases (n = 740) were Caucasian women with incident breast cancer identified from all major hospitals in Erie and Niagara counties. Community controls (n = 810) were frequency matched to cases by age and county. An in-depth interview including a validated FFQ was administered in person. Odds ratios (ORs) and 95% CIs were used to estimate relative risks. Consumption of cruciferous vegetables, particularly broccoli, was marginally inversely associated with breast cancer risk in premenopausal women [4th quartile OR = 0.6, 95% CI (0.40-1.01), P = 0.058]. Associations were weaker or null among postmenopausal women. No significant effects of GST genotype on risk were observed in either menopausal group. These data indicate that cruciferous vegetables may play an important role in decreasing the risk of premenopausal breast cancer.

Alcohol drinking in light-to-moderate amounts has been associated with reduced coronary heart disease (CHD) risk. However, there is evidence that the way people consume alcohol (drinking pattern) may affect risk. Central adiposity, a known CHD risk factor may be one mechanism in the pathway between alcohol consumption and CHD risk. Our study examined whether various drinking patterns differentially affect fat distribution, particularly abdominal fat in women and men. In a randomly selected population-based cohort (n = 2343), 35-79 y old, we assessed drinking pattern as reported for the past 30 d, including beverage type and amount, frequency of consumption, percentage of time drinking while eating and number of drinks consumed/drinking day. Central adiposity was determined using an abdominal caliper to measure supine height of the abdomen. Current drinkers tended to have smaller abdominal heights than nondrinkers (women, P < 0.0001; men, P = 0.0559). For drinking pattern, frequency was inversely associated, but drinking intensity (drinks/drinking day) was positively associated with central adiposity in women (P trend for frequency, 0.0007; intensity, 0.0010) and men (P trend for frequency, 0.0005; intensity, 0.0004), even when age, education, physical activity, smoking status and amount of alcohol (g) were included in the models. When frequency and intensity were considered together, daily drinkers of

Lignans are plant compounds metabolized in the gut to produce the phytoestrogens enterolactone and enterodiol. Reduced breast cancer risks associated with higher urinary lignan excretion may be related to competitive inhibition of endogenous estrogens. Evidence exists that associations with reproductive risk factors for breast cancer differ according to cytochrome P450c17alpha (CYP17) genotype. Genetic variability in estrogen metabolism could affect lignan metabolism thereby modifying risk associations. We examined breast cancer risk, dietary lignans and CYP17 genotype among 207 women with primary, incident, histologically confirmed breast cancer and 188 controls frequency matched to cases by age and county of residence. Self-reported frequency of intake of 170 foods and beverages during the 2 y before the interview and other relevant data were collected by detailed in-person interviews. Dietary lignan intake was expressed as the sum of enterolactone and enterodiol production from foods. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression, adjusting for age, education and other breast cancer risk factors. Women in the highest tertile of dietary lignans tended to have reduced breast cancer risk (OR 0.45, 95% CI 0.20-1.01 and OR 0.59, 95% CI 0.28-1.27, pre- and postmenopausal women, respectively). Substantially reduced risks in the highest tertile of lignans were observed for premenopausal women with at least one A2 allele (OR 0.12, 95% CI 0.03-0.50). Our results suggest that CYP17 genotype may be important in modifying the effect on breast cancer risk of exogenous estrogens, particularly for premenopausal women.

Increasingly the role of diet in the etiology of chronic disease has been the focus of research. Reviewed here are the epidemiologic study designs used for such research and the methodologies used for measurement of diet. Strengths and weaknesses of ecologic, cross-sectional, case-control cohort studies and clinical trials are discussed. Additionally the advantages and disadvantages of dietary recalls, food records, diet histories and food frequency questionnaires are reviewed as pertains to their use in nutritional epidemiology research.