Meera Jain

Plant Foods, Antioxidants, and Prostate Cancer Risk: Findings From Case-Control Studies in Canada

Epidemiological data on most cancer sites suggest that consumption of plant foods, which contain high levels of antioxidants, might slow or prevent the appearance of cancer. We used data from three case-control studies to test this hypothesis. The total study population consisted of 617 incident cases of prostate cancer and 636 population controls from Ontario, Quebec, and British Columbia. Dietary information was collected by an in-person interview with a detailed quantitative dietary history. Unconditional logistic regression analyses were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A decreasing, statistically significant association was found with increasing intakes of green vegetables (OR = 0.54, 95% CI = 0.40-0.71 for 4th quartile), tomatoes (OR = 0.64, 95% CI = 0.45-0.91), beans/lentils/nuts (OR = 0.69, 95% CI = 0.53-0.91), and cruciferous vegetables (OR = 0.69, 95% CI = 0.52-0.91 for 3rd quartile). Higher intakes of fruit were associated with higher ORs (OR = 1.51, 95% CI = 1.14-2.01 for 4th quartile), an effect that was seen for total fruit and citrus fruit, as well as for all other noncitrus fruits. Among the grains, refined-grain bread intake was associated with a decrease in risk (OR = 0.65 for 4th quartile), whereas whole-grain breakfast cereals were associated with a higher risk for prostate cancer. Of all the antioxidant nutrients studied, the ORs were higher with higher intakes of cryptoxanthin (OR = 1.44, 95% CI = 1.09-1.89 for 4th quartile). Exposure to certain dietary components of plant origin, which are potentially modifiable, indicates the theoretical scope for reducing the risk from prostate cancer. Future experimental studies or trials are warranted for further understanding.

Dietary fiber, vitamins A, C, and E, and risk of breast cancer: a cohort study

Risk of breast cancer was examined in relation to intake of dietary fiber and vitamins A, C, and E, and food groups which are sources of these dietary constituents, in a cohort of 56,837 women enrolled in the Canadian National Breast Screening Study. Between 1982 and 1987, 519 incident, histologically confirmed cases of breast cancer were identified among women who previously had completed self-administered dietary questionnaires. Their nutrient and food intake was compared with that of 1,182 women who had not developed breast cancer during the follow-up period. Women at the uppermost quintile level of dietary fiber intake had a 30 percent reduction in risk of breast cancer relative to that for women at the lowest quintile level (adjusted odds ratio = 0.68,95 percent confidence interval = 0.46–1.00), and the reduction in risk persisted after adjustment (separately) for total vitamin A, β-carotene, vitamin C, and α-tocopherol. Inverse associations of similar magnitude were observed in association with consumption of pasta, cereals (the trend for which was statistically significant), and vegetables rich in vitamins A and C. Smaller, statistically nonsignificant reductions in risk were observed with increasing intake of dietary retinol, β-carotene, and vitamin C, but the magnitude of these associations was reduced after adjustment for other dietary factors. Vitamin E intake was not associated with altered risk of breast cancer.

A cohort study of nutritional factors and endometrial cancer.

To evaluate the role of nutritional factors in the etiology of endometrial cancer, we performed a case-cohort analysis using data from women enrolled in the National Breast Screening Study in Canada from 1980 to 1985. For this analysis, a subcohort was constructed by selecting a 10% random sample from the 56,837 women in the dietary cohort. Cases were the 221 women diagnosed with incident adenocarcinoma of the endometrium during follow-up to December 31, 1993 and ascertained by record linkage to the Canadian Cancer Database. Information on usual diet at enrolment and other epidemiological variables was collected by means of self-administered questionnaires. Hazard ratios were obtained from proportional hazards regression models, with estimation of robust standard errors. We found a strong association of endometrial cancer with body mass index >25 kg/m2 (hazard ratio 2.72, 95% CI: 2.06–3.50). Endometrial cancer risk was not associated significantly with intakes of total energy, carbohydrates, proteins, total fat and major fatty acids, total dietary fiber and various types of fibers, vitamin C, E and A, folic acid, β-carotene, lutein, or cryptoxanthin. Some decrease in risk was noted with relatively high intakes of saturated fat, animal fat or lycopene. The associations observed in the study were independent of total energy intake and most non-dietary risk factors. The study suggests that dietary intakes of energy and most major nutrients are not related to the risk of endometrial cancer among Canadian women.

Dietary intake of folic acid and colorectal cancer risk in a cohort of women.

Folate is crucial for normal DNA methylation, synthesis and repair, and deficiency of this nutrient is hypothesized to lead to cancer through disruption of these processes. There is some evidence to suggest that relatively high dietary folate intake might be associated with reduced colorectal cancer risk, especially among individuals with low methionine intake. A case‐cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self‐administered dietary questionnaire. During follow‐up to the end of 1993, a total of 389 women were diagnosed with colorectal cancer, identified by linkage to the Canadian Cancer Database. For comparative purposes, a subcohort of 5,681 women was randomly selected from the full dietary cohort at baseline. After exclusions for various reasons, the analyses were based on 295 cases and 5,334 non‐cases. Folate intake was inversely associated with colorectal cancer risk (IRR = 0.6, 95% CI = 0.4–1.1, p for trend = 0.25). The inverse association was essentially similar among individuals with low and high methionine intake, and was similar for colon and rectal cancers when those endpoints were analyzed separately. Among individuals with low methionine intake, folate intake did not appear to lower the risk of rectal cancer, a finding that may be due, in part, to the low number of cases in the subgroup analysis. Overall, our data lend some support to the hypothesis that high folate intake is associated with a reduced risk of colorectal cancer.

Dietary carbohydrates and breast cancer risk: A prospective study of the roles of overall glycemic index and glycemic load

We examined breast cancer risk in association with overall glycemic index (GI), glycemic load (GL), and dietary carbohydrate and sugar intake in a prospective cohort of 49,613 Canadian women enrolled in the National Breast Screening Study who completed a self‐administered food frequency questionnaire between 1980 and 1985. Linkages to national mortality and cancer databases yielded data on deaths and cancer incidence, with follow‐up ending between 1998 and 2000. During a mean follow‐up of 16.6 years, we observed 1,461 incident breast cancer cases. GI, GL, total carbohydrate and total sugar intake were not associated with breast cancer risk in the total cohort. However, there was evidence of effect modification of the association between GI and breast cancer risk by menopausal status (p = 0.01), the hazard ratio for the highest versus the lowest quintile level of GI being 0.78 (95% CI = 0.52–1.16; ptrend = 0.12) in premenopausal women and 1.87 (95% CI = 1.18–2.97; ptrend = 0.01) in postmenopausal women. The associations between GI and GL were not modified by body mass index (BMI) or by vigorous physical activity among pre‐ or postmenopausal women. Similarly, the associations between GI/GL and risk in postmenopausal women were not modified by BMI, vigorous physical activity, or ever use of hormone replacement therapy (HRT), although the associations were slightly stronger among those who reported no vigorous physical activity (ptrend = 0.02), among those who reported ever using HRT (ptrend = 0.02) and among normal‐weight women (BMI < 25 kg/m2; ptrend = 0.03). Our data suggest that consumption of diets with high GI values may be associated with increased risk of breast cancer among postmenopausal women, possibly more so among subgroups defined by participation in vigorous physical activity, ever use of HRT and those who are not overweight.

Dietary intake of selected B vitamins in relation to risk of major cancers in women

Although folic acid has been investigated for its potential to inhibit carcinogenesis, few epidemiologic studies have assessed the effects of intake of thiamin, riboflavin, and niacin, which may reduce cancer risk by acting as cofactors in folate metabolism or by other mechanisms. Using data from a large cohort of Canadian women, we examined the association of dietary intake of these nutrients, as well as intake of folate, methionine, and alcohol, with cancers of the breast, endometrium, ovary, colorectum, and lung ascertained during an average of 16.4 years of follow-up. After exclusions, the following numbers of incident cases were available for analysis: breast, n=2491; endometrium, n=426; ovary, n=264; colorectum, n=617; and lung, n=358. Cox proportional hazard models were used to estimate risk of each cancer with individual nutrients and to explore possible effect modification by combinations of nutrients on cancer risk. Few significant associations of intake of individual B vitamins with the five cancers were observed. Alcohol consumption showed a modest positive association with breast cancer risk but not with risk of the other cancers. There was no evidence of effect modification among the nutrients. This large study provides little support for an association of dietary intake thiamin, riboflavin, niacin, folate, or methionine with five major cancers in women.

A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women

In a cohort study of 49 654 Canadian women, we assessed the association of colorectal cancer with total iron and heme iron intake, excluding iron supplements. Among women aged 40–59 years, followed for an average of 16.4 years, we identified 617 incident colorectal cancer cases. Data from a food frequency questionnaire administered at baseline were used to calculate red meat intake and intake of total dietary iron, iron from meat, and heme iron. Analyses were carried out for all cases and for the proximal colon, distal colon, and rectum, using Cox proportional hazards models. We found no association of intake of iron, heme iron, or iron from meat with risk of colorectal cancer overall or with any of the subsites, nor was there effect modification by alcohol consumption or hormonal replacement therapy.

Alcohol consumption and risk of breast cancer: a cohort study.

AbstractObjectives: To study the association between alcohol consumption and breast cancer risk. Methods: A case–cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40–59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases. Results: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming > 0 and  ≤ 10 g of alcohol/day,  > 10 and  ≤ 20 g/day,  > 20 and  ≤thinsp;30 g/day,  > 30 and  ≤ 40 g/day,  > 40 and  ≤ 50 g/day, and  > 50 g/day were 1.01 (0.84–1.22), 1.16 (0.91–1.47), 1.27 (0.91–1.78), 0.77 (0.51–1.16), 1.00 (0.57–1.75), and 1.70 (0.97–2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors. Conclusions: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.

Agreement of self-reported use of menopausal hormone replacement therapy with physician reports.

There have been relatively few epidemiological studies to verify the information obtained from study participants on the use of menopausal hormone replacement therapy. We conducted this study as part of a case-control study of diet, hormone use, and endometrial cancer in Toronto, Ontario, Canada, 1994-1998. We compared records from 653 subjects, 30-79 years of age, with reports from their physicians on ever/never use of hormone replacement therapy and duration, type, and dose of hormone replacement therapy. A total of 88% of the interview records were in agreement with physician reports for ever/never use of hormone replacement therapy. The overall kappa value for ever/never use agreement was 0.76 (range = 0.71-0.81), and the intraclass correlation coefficient was 0.64 (range = 0.57-0.70) for duration of hormone replacement therapy use, indicating good agreement; similar correlations were seen among cases and controls for overall use, as well as estrogen- or progestogen-alone use. Concordance for brand codes was observed for about 43% of the subjects. This study suggests that information obtained by interview in case-control studies provides a reasonable measure of ever use of hormone replacement therapy and duration of use. Interviews, however, do not represent a reliable source of information on brands and dosage of hormone replacement therapy preparations.

Tumor characteristics and survival of breast cancer patients in relation to premorbid diet and body size

Nutritional factors have been suggested to play an important role in the prognosis of breast cancer through their effect on tumor characteristics. This study evaluated four tumor characteristics and prognosis in relation to premorbid diet and body size. From a cohort of 89,835 women in the National Breast Screening Study (NBSS) in Canada, data on 676 incident cases of invasive carcinoma of breast, on whom we had dietary information, were used. A high energy intake lowered the likelihood of being ER positive and PR positive but after adjusting for ER status, was still associated with a higher risk of dying of breast cancer. Total fat and various types of fats were associated with a greater likelihood that a woman would be ER and PR positive, however the likelihood of dying from breast cancer was higher with higher fat consumption. There was no significant effect of higher intakes of beta carotene or vitamin C on ER status, nodal status or tumor size, but a significantly lower risk of dying from breast cancer was observed. Higher intake of carbohydrates and calcium was associated with a lowered frequency of ER and PR positive status but also with a lower risk of dying. Of the five indicators of body size studied, higher triceps skinfold thickness was associated with a slightly lower chance of being ER positive, PR positive, and node negative, and a significantly higher likelihood of dying. It appears that while there are significant associations between some of the diet and body size variables and tumor characteristics, the effect of most nutritional factors on prognosis in breast cancer may not be mediated via their effect on tumor characteristics.