Purpose: Because they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake.Patients and Methods: A total of 24,226 women ages 40 to 69 years in the Japan Public Health Center–based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model.Results: We found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein.Conclusion: This nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.

Importance: Despite evidence of an association between reproductive factors and endometrial cancer risk, prospective studies have been conducted mainly in non-Asian countries.Objective: To assess the association between reproductive factors, such as number of deliveries, age at menarche, or menopause, and endometrial cancer risk.Design, Setting, and Participants: This cohort study used pooled individual data from 13 prospective cohort studies conducted between 1963 and 2014 in the Asia Cohort Consortium. Participants were Asian women. Data analysis was conducted from September 2019 to April 2023.Exposures: Reproductive factors were assessed using a questionnaire in each cohort.Main Outcomes and Measures: The main outcome was time to incidence of endometrial cancer. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% CIs.Results: A total of 1005 endometrial cancer cases were detected among 332 625 women (mean [SD] age, 54.3 [10.4] years) during a mean (SD) of 16.5 (6.4) years of follow-up. Increasing number of deliveries was associated with a decreased endometrial cancer risk in a dose-response manner (≥5 deliveries vs nulliparous [reference]: HR, 0.37; 95% CI, 0.26-0.53; P for trend < .001). Compared with menarche at younger than 13 years, menarche at 17 years or older had an HR of 0.64 (95% CI, 0.48-0.86; P for trend < .001). Late menopause (age ≥55 years) showed an HR of 2.84 (95% CI, 1.78-4.55; P for trend < .001) compared with the youngest age category for menopause (<45 years). Age at first delivery, hormone therapy, and breastfeeding were not associated with endometrial cancer risk.Conclusions and Relevance: This large pooled study of individual participant data found that late menarche, early menopause, and a higher number of deliveries were significantly associated with a lower risk of endometrial cancer. These convincing results from Asian prospective studies add to the growing body of evidence for the association between reproductive factors and endometrial cancer.

Background: Several studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between5,10-methylenetetrahydrofolate reductase (MTHFR)andmethionine synthase(MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated.Methods: A case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B₆, and vitamin B₁₂were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed forMTHFRA1298C and C677T, andMTRA2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: Neither dietary intake of folate, vitamin B₆, or vitamin B₁₂norMTHFRpolymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23–3.83;P_trend= 0.010). TheMTR2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01–3.92;P_trend= 0.801), and statistically significant interactions with regard to risk were observed between theMTHFRA1298C polymorphism and folate (P = 0.024) or vitamin B₆(P = 0.043), and between theMTHFRC677T polymorphism and folate (P = 0.043) or vitamin B₁₂(P = 0.022).Conclusion: MTHFRpolymorphisms and dietary intake of folate, vitamin B₆, and vitamin B₁₂had no overall association with breast cancer risk. However, increased risk was observed in total women with theMTR2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions betweenMTHFRpolymorphisms and B vitamins, warrant further investigation.