Beatrice A. Boucher

Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan.

Abstract: Phytoestrogens may play a role in hormone-related diseases such as cancer, but epidemiological and clinical data are conflicting in part due to inadequate databases used in intake estimation. A database of nine phytoestrogens in foods relevant to Western diets was developed to more accurately estimate intakes. Foods (N = 121) available in Ontario, Canada were prepared as commonly consumed and analyzed for isoflavones (genistein, daidzein, glycitein, formononetin), lignans (secoisolariciresinol, matairesinol, pinoresinol, lariciresinol), and coumestan (coumestrol) using gas chromatography-mass spectrometry methods. Data were presented on an as is (wet) basis per 100 g and per serving. Food groups with decreasing levels of total phytoestrogens per 100 g are nuts and oilseeds, soy products, cereals and breads, legumes, meat products, and other processed foods that may contain soy, vegetables, fruits, alcoholic, and nonalcoholic beverages. Soy products contain the highest amounts of isoflavone, followed by legumes, meat products and other processed foods, cereals and breads, nuts and oilseeds, vegetables, alcoholic beverages, fruits, and nonalcoholic beverages. Decreasing amounts of lignans are found in nuts and oilseeds, cereals and breads, legumes, fruits, vegetables, soy products, processed foods, alcoholic, and nonalcoholic beverages. The richest sources of specific phytoestrogens, including coumestrol, were identified. The database will improve phytoestrogen intake estimation in future epidemiological and clinical studies particularly in Western populations.

Validity and reliability of the Block98 food-frequency questionnaire in a sample of Canadian women.

OBJECTIVE To assess the validity and reliability of the most recent adaptation of Blocks full-diet food-frequency questionnaire (FFQ) among a sample of Canadian women. DESIGN Participants completed a self-administered FFQ (FFQ1), two unannounced 24-hour recalls (weekday and weekend) and a second FFQ (FFQ2) between October 2003 and February 2004. FFQs and recalls were analysed for 32 nutrients using Block Dietary Data Systems and the University of Minnesotas Nutrient Data System. Mean and median intakes were computed, along with crude and deattenuated Pearson correlation coefficients between FFQ1 and the average of two recalls (validity) and between FFQ1 and FFQ2 (reliability). SETTING Ontario, Canada. SUBJECTS A random population-based sample (n = 166) of women aged 25 to 74 years. RESULTS One hundred and fifteen (69%) women completed FFQ1, 96 completed FFQ1 and both recalls, and 93 completed both FFQs, about 56 days apart. Mean intakes were similar for most nutrients. FFQ reliability was high, with Pearson correlation coefficients having a median of 0.75, ranging from 0.57 to 0.90 (macronutrients) and from 0.65 to 0.88 (micronutrients from supplements and food). FFQ validity was moderate to high, with deattenuated Pearson correlation coefficients having a median of 0.59, ranging from 0.11 to 0.73 (macronutrients) and from 0.50 to 0.76 (micronutrients from supplements and food). Our micronutrient correlations were similar to or higher than those of other studies that included supplements. Two correlations <0.40 were associated with fats. CONCLUSIONS The validity and reliability of this full-diet version of the Block FFQ were moderate to high, supporting its use in future studies among Canadian women.

Red meat intake, doneness, polymorphisms in genes that encode carcinogen-metabolizing enzymes and colorectal cancer risk

Colorectal cancer literature regarding the interaction between polymorphisms in carcinogen-metabolizing enzymes and red meat intake/doneness is inconsistent. A case-control study was conducted to evaluate the interaction between red meat consumption, doneness, and polymorphisms in carcinogen-metabolizing enzymes. Colorectal cancer cases diagnosed 1997 to 2000, ages 20 to 74 years, were identified through the population-based Ontario Cancer Registry and recruited by the Ontario Family Colorectal Cancer Registry. Controls were sex-matched and age group-matched random sample of Ontario population. Epidemiologic and food questionnaires were completed by 1,095 cases and 1,890 controls; blood was provided by 842 and 1,251, respectively. Multivariate logistic regression was used to obtain adjusted odds ratio (OR) estimates. Increased red meat intake was associated with increased colorectal cancer risk [OR (>5 versus ≤2 servings/wk), 1.67 (1.36-2.05)]. Colorectal cancer risk also increased significantly with well-done meat intake [OR (>2 servings/wk well-done versus ≤2 servings/wk rare-regular), 1.57 (1.27-1.93)]. We evaluated interactions between genetic variants in 15 enzymes involved in the metabolism of carcinogens in overcooked meat (cytochrome P450, glutathione S-transferase, UDP-glucuronosyltransferases, SULT, NAT, mEH, and AHR). CYP2C9 and NAT2 variants were associated with colorectal cancer risk. Red meat intake was associated with increased colorectal cancer risk regardless of genotypes; however, CYP1B1 combined variant and SULT1A1-638G>A variant significantly modified the association between red meat doneness intake and colorectal cancer risk. In conclusion, well-done red meat intake was associated with an increased risk of colorectal cancer regardless of carcinogen-metabolizing genotype, although our data suggest that persons with CYP1B1 and SULT1A1 variants had the highest colorectal cancer risk. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3098–107)

Phytoestrogen intake from foods, during adolescence and adulthood, and risk of breast cancer by estrogen and progesterone receptor tumor subgroup among Ontario women

Phytoestrogen intake may reduce breast cancer risk and limited evidence suggests this association may hold for hormone receptor‐positive tumors only. The study aims were to assess whether the association between phytoestrogen intake during adolescence and adulthood and breast cancer risk varies by estrogen and progesterone receptor (ERPR) tumor subgroup. Cases were identified from the Ontario Cancer Registry (2002–2003), and ERPR status was ascertained from pathology reports for 81% of cases (n = 2,438). Controls were identified through random digit dialing of Ontario households (n = 3,370). Published phytoestrogen food values were applied to food frequency questionnaire responses to assess isoflavone, lignan and total phytoestrogen intake, during adolescence and adulthood. Polytomous multivariate logistic regression was used to estimate adjusted odds ratios (ORs) for association between phytoestrogen intake and breast cancer risk by hormone receptor ERPR tumor subgroups. Among premenopausal women, few associations were observed for adolescent or adult phytoestrogen intake across all tumor subgroups. Among postmenopausal women, adolescent phytoestrogen intake (isoflavone, lignan and total) was associated with reduced risk across all hormone receptor subgroups; however, statistical significance was most consistent within the ER+PR+ subgroup. For example, ER+PR+ postmenopausal breast cancer risk was associated with adolescent phytoestrogen intake (highest vs. lowest: OR = 0.79; 95% confidence interval: 0.65–0.96). Among all women and postmenopausal women, ORs for high adult lignan intake were all below 1.0 within each tumor subgroup, suggesting reduced breast cancer risk, although none reached statistical significance. In conclusion, adolescent phytoestrogen intake was associated with reduced postmenopausal breast cancer, particularly for ER+PR+ tumor subgroup.

Dietary Phytoestrogens, Including Isoflavones, Lignans, and Coumestrol, in Nonvitamin, Nonmineral Supplements Commonly Consumed by Women in Canada

Abstract Twenty-one nonvitamin, nonmineral dietary supplements commonly consumed by women in Canada were analyzed for isoflavones (formononetin, daidzein, genistein, glycitein), lignans (pinoresinol, lariciresinol, secoisolariciresinol, matairesinol), and coumestrol to complement our previously published food phytoestrogen database. Supplements containing soy or red clover had the highest concentrations of total isoflavones (728.2–35,417.0 ug/g) and total phytoestrogens (1030.1–35,517.7 ug/g) followed by licorice and licorice-containing supplements (41.3–363.3 ug/g isoflavones; 56.5–370.0 ug/g total phytoestrogens). Other supplements had considerably less isoflavones (≤ 19.0 ug/g) and total phytoestrogens (≤ 44.2 ug/g). Lignans were present in all (≤ 298.9 ug/g), whereas coumestrol was either not present or present in only small amounts (≤ 3.0 ug/g). Supplements differed in phytoestrogen profiles. The daily intake of isoflavones and lignans from some supplements may greatly exceed those from several servings of soy or vegetables. Hence, the intake of supplements should be taken into consideration in clinical or epidemiological studies for more accurate estimation of phytoestrogen intakes.

Intake of Phytoestrogen Foods and Supplements Among Women Recently Diagnosed With Breast Cancer in Ontario, Canada

Phytoestrogens are found in foods such as soy (isoflavones) and flaxseed (lignans), and certain botanical supplements. Their role in estrogen receptor positive (ER+) breast cancer recurrence and treatment is controversial, and it is unknown how this affects intake among patients. The Ontario Cancer Registry was used to identify 417 population-based breast cancer cases (mean time from diagnosis was 57 days). A questionnaire was mailed to determine intake of phytoestrogen foods and supplements in the last 2 mo, changes since diagnosis and differences by ER tumor status or hormonal treatment. Of 278 (67%) respondents, 56% consumed soy foods, 39% consumed isoflavone-rich foods (tofu, soybeans, soy milk, soy nuts), and 70% ate lignan-rich foods, including flaxseed (33%). Only soy milk, flaxseed, and flaxseed bread were commonly consumed more than once/wk. Few patients (4%) took isoflavone (soy, red clover, kudzu, licorice, isoflavones) or lignan/flaxseed supplements. Since diagnosis, 17% started or stopped soy foods (most stopped); this was more prevalent among those receiving hormonal treatment (20%; 95% confidence interval (CI): 14, 26) than not (6%; 95% CI: 1, 12). No other differences by ER status or hormonal treatment were observed. Research is needed to confirm this and to explore influencing factors.

High Coffee Intake, but Not Caffeine, is Associated with Reduced Estrogen Receptor Negative and Postmenopausal Breast Cancer Risk with No Effect Modification by CYP1A2 Genotype

Associations between caffeine and coffee consumption and breast cancer risk are uncertain, with studies suggesting inverse and null associations. Variation in cytochrome P450 1A2 (CYP1A2), a gene responsible for caffeine metabolism, may modify these associations. Cases (n = 3,062) were recruited through the Ontario Cancer Registry and controls (n = 3,427) through random digit dialing. Logistic regression was used to evaluate associations between breast cancer risk and intakes of 7 caffeine-containing items and total caffeine, and examine whether a genetic variant in CYP1A2 (rs762551) modified these associations. Analyses were stratified by estrogen receptor (ER), menopausal, and smoking status. Generally, coffee and caffeine were not associated with breast cancer risk; however, a significant reduction in risk was observed with the highest category of coffee consumption [≥5 cups per day vs. never, multivariate-adjusted odds ratio (MVOR) = 0.71, 95% confidence interval (CI): 0.51, 0.98]. Variant rs762551 did not modify associations. In stratified analyses, high coffee intake was associated with reduced risk of ER- (MVOR = 0.41, 95% CI: 0.19, 0.92) and postmenopausal breast cancer (MVOR = 0.63, 95% CI: 0.43, 0.94). High coffee consumption, but not total caffeine, may be associated with reduced risk of ER- and postmenopausal breast cancers, independent of CYP1A2 genotype. Further studies are needed to replicate these findings.

Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk

Botanical supplements are widely used and contain diverse ingredients, including isoflavones. Food‐based isoflavones have been associated with reduced breast cancer risk. However, no study has comprehensively evaluated supplements identified by isoflavone content and breast cancer risk. Associations between ever use of 28 isoflavone supplements and breast cancer risk in Ontario, Canada were evaluated using cases (n = 3,101) identified in 2002–2003 from the Ontario Cancer Registry and controls (n = 3,471) identified through random digit dialing methods. Multivariate logistic regression was used to estimate age‐adjusted odds ratio (AOR) and 95% confidence intervals (CI). Several individual supplements were associated with reduced breast cancer risk (e.g., Natural HRT; AOR = 0.39; 95% CI: 0.22, 0.69; nusers = 58). Use of any isoflavone supplements was associated with reduced risk when ≥3 were ever used (AOR = 0.68; 95% CI: 0.54, 0.86; nusers = 332; ptrend = 0.008) or any was taken >5 years (AOR = 0.75; 95% CI: 0.60, 0.94; nusers = 325; ptrend = 0.01); high content supplements were consistently associated with reduced risk. Risk reduction was confined to postmenopausal breast cancer for both individual and combined supplements, and was strongest in the latter among high content users who ever took ≥3 supplements (AOR = 0.55; 95% CI: 0.38, 0.81; nusers = 118; ptrend = 0.04) or any >5 years (AOR = 0.47; 95% CI: 0.27, 0.81; nusers = 60; ptrend = 0.03). Associations did not differ by estrogen‐progesterone tumor receptor status. In conclusion, isoflavone supplements were associated with decreased postmenopausal breast cancer risk. Further research to examine these novel findings is warranted, given the low supplement use and potential limitations of our results.

Using national dietary intake data to evaluate and adapt the US Diet History Questionnaire: the stepwise tailoring of an FFQ for Canadian use.

OBJECTIVE To evaluate the Canadian Diet History Questionnaire I (C-DHQ I) food list and to adapt the US DHQ II for Canada using Canadian dietary survey data. DESIGN Twenty-four-hour dietary recalls reported by adults in a national Canadian survey were analysed to create a food list corresponding to C-DHQ I food questions. The percentage contribution of the food list to the total survey intake of seventeen nutrients was used as the criterion to evaluate the suitability of the C-DHQ I to capture food intake in Canadian populations. The data were also analysed to identify foods and to modify portion sizes for the C-DHQ II. SETTING The Canadian Community Health Survey (CCHS) - Cycle 2.2 Nutrition (2004). SUBJECTS Adults (n 20 159) who completed 24 h dietary recalls during in-person interviews. RESULTS Four thousand five hundred and thirty-three foods and recipes were grouped into 268 Food Groups, of which 212 corresponded to questions on the C-DHQ I. Nutrient intakes captured by the C-DHQ I ranged from 79 % for fat to 100 % for alcohol. For the new C-DHQ II, some food questions were retained from the original US DHQ II while others were added based on foods reported in CCHS and foods available on the Canadian market since 2004. Of 153 questions, 143 were associated with portion sizes of which fifty-three were modified from US values. Sex-specific nutrient profiles for the C-DHQ II nutrient database were derived using CCHS data. CONCLUSIONS The C-DHQ I and II are designed to optimize the capture of foods consumed by Canadian populations.

Dietary assessment is a critical element of health research – Perspective from the Partnership for Advancing Nutritional and Dietary Assessment in Canada

Challenges and complexities associated with assessing dietary intakes are numerous, but not insurmountable. This opinion paper from Canadian researchers draws attention to the importance of building capacity and providing funding opportunities for research in dietary assessment methods in Canada and elsewhere. Such strategies would contribute to a better understanding of the roles played by diet in human health and better translation of this information into the most meaningful and effective dietary guidelines, policies, and interventions.