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In studies of anthropometric measures and prostate cancer risk, conducted primarily in White men, positive associations with advanced disease have been reported. We assessed body size in relation to incident prostate cancer risk in 79,950 men from the Multiethnic Cohort, with 8,819 cases identified over 22 years (1993–2015). Height was associated with increased risk of advanced prostate cancer (≥68 inches (≥ 173 cm) vs. < 66 inches (168 cm); hazard ratio (HR) = 1.24, 95% confidence interval (CI): 1.04, 1.48) and high-grade disease (HR = 1.15, 95% CI: 1.02, 1.31). Compared with men of normal weight, men overweight at baseline were at higher risk of high-grade cancer (HR = 1.15, 95% CI: 1.04, 1.26). Greater weight was positively associated with localized and low-grade disease in Blacks and Native Hawaiians (by race, P for heterogeneity = 0.0002 and 0.008, respectively). Weight change since age 21 years was positively associated with high-grade disease (for ≥ 40 pounds (18 kg) vs. 10 pounds (4.5 kg), HR = 1.20, 95% CI: 1.05, 1.37; P for trend  =  0.005). Comparing highest versus lowest quartile, waist-to-hip ratio was associated with a 1.78-fold increase (95% CI: 1.28, 2.46) in the risk of advanced prostate cancer. Positive associations with the majority of anthropometric measures were observed in all 5 racial/ethnic groups, suggesting a general impact of anthropometric measures on risk across populations. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive vs nonaggressive disease.Methods: Participants were 5545 European-ancestry men, including 2775 nonaggressive and 2770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency < 0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared single variant, gene-based, and DNA repair pathway-based burdens by disease aggressiveness. All statistical tests are 2-sided.Results: BRCA2 and PALB2 had the most statistically significant gene-based associations, with 2.5% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D BRCA2 alleles (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.94 to 5.25, P = 8.58 × 10-7) and 0.65% of aggressive and 0.11% of nonaggressive cases carrying P/LP/D PALB2 alleles (OR = 6.31, 95% CI = 1.83 to 21.68, P = 4.79 × 10-4). ATM had a nominal association, with 1.6% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D ATM alleles (OR = 1.88, 95% CI = 1.10 to 3.22, P = .02). In aggregate, P/LP/D alleles within 24 literature-curated candidate PCa DNA repair genes were more common in aggressive than nonaggressive cases (carrier frequencies = 14.2% vs 10.6%, respectively; P = 5.56 × 10-5). However, this difference was non-statistically significant (P = .18) on excluding BRCA2, PALB2, and ATM. Among these 24 genes, P/LP/D carriers had a 1.06-year younger diagnosis age (95% CI = -1.65 to 0.48, P = 3.71 × 10-4).Conclusions: Risk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. These findings support the importance of these genes in both screening and disease management considerations. [ABSTRACT FROM AUTHOR]

Observational epidemiological studies and randomized trials have reported a protective effect of estrogen and progestin therapy (EPT) on the risk of colorectal cancer but the findings on estrogen-alone therapy (ET) are less consistent. The mechanism by which menopausal hormones influence risk of colorectal cancer has not been well studied. To further investigate the relationship between menopausal hormones and risk of colon cancer, we conducted a population-based case–control study in Los Angeles County involving 831 women with newly diagnosed colon cancer and 755 population-based control women. Risk of colon cancer decreased significantly with increasing duration of current use of ET and EPT; the adjusted relative risk was 0.83 [95% confidence interval (95% CI) = 0.76–0.99)] per 5 years of ET use and 0.88 (95% CI = 0.78–0.99) per 5 years of EPT use. Risk of colon cancer was unrelated to past ET or EPT use. We explored if current use of menopausal hormones is associated with DNA methylation of estrogen receptor (ESR1 and ESR2), progesterone receptor and other genes in the colonic tissues of a subset of colon cancer patients (n = 280) we interviewed. Our results suggest that current menopausal hormone users compared with non-current users displayed increased DNA methylation of progesterone receptor in the ‘normal’ colonic tissues (P = 0.055) and increased DNA methylation of ESR1 in the ‘tumorous’ colonic tissues (P = 0.056). These findings on DNA methylation and hormone therapy use need confirmation in larger studies. [ABSTRACT FROM PUBLISHER]

The association between soyfood intake and breast cancer risk is controversial. Most of the epidemiologic studies published on this topic in the 1990s were not designed to specifically address this question. We conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County to further investigate the role of soy. Our primary objective was to quantify breast cancer risks associated with intake of soy during adolescence and adult life among Asian-American women. During 1995–1998, we successfully interviewed 501 breast cancer patients and 594 control subjects. Intake of soy among Asian-Americans is still relatively high; the median intake was 12 mg isoflavones/day, approximately one-third of that reported in a recent study in Shanghai, China. The risk of breast cancer was significantly inversely associated with soy intake during adolescence and adult life. After adjusting for age, specific Asian ethnicity, education, migration history and menstrual and reproductive factors, women who reported soy intake at least once per week during adolescence showed a statistically significantly reduced risk of breast cancer. There was also a significant trend of decreasing risk with increasing soy intake during adult life. When we considered soy intake during both adolescence and adult life, subjects who were high-soy consumers during both time periods showed the lowest risk (OR=0.53, 95% CI=0.36–0.78) compared with those who were low consumers during both time periods. Risk of breast cancer was intermediate among subjects who were high-soy consumers during adolescence and low-soy consumers during adult life (OR=0.77, 95% CI=0.51–1.10). Based on a relatively small number of subjects, the risk did not appear to differ between those who were low consumers during adolescence and high consumers during adult life. Results remained similar after adjustment for other potential confounders including other dietary and non-dietary risk factors for breast cancer. These results show that high soy intake in childhood in Asian-Americans is associated with reduced breast cancer risk. Risk may be further reduced by intake as an adult. [ABSTRACT FROM PUBLISHER]