Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three novel susceptibility loci were revealed at P<5×10-8; 15 variants were identified among men of European ancestry, 7 from multiethnic analyses and one was associated with early-onset prostate cancer. These 23 variants, in combination with the known prostate cancer risk variants, explain 33% of the familial risk of the disease in European ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the utility of combining ancestrally diverse populations to discover risk loci for disease.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 [95% confidence interval (CI) 4.84–5.29] for men of European ancestry to 3.74 [95% CI 3.36–4.17] for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher [95% CI 2.14–2.22], and men of East Asian ancestry 0.73-times lower [95% CI 0.71–0.76], than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

This study provides strong evidence that the addition of a progestin to HRT enhances markedly the risk of breast cancer relative to estrogen use alone. These findings have important implications for the risk-benefit equation for HRT in women using CHRT.

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.

Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 × 10−10). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 × 10−9), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 × 10−9). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.