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There is suggestive epidemiologic evidence that high soy intake may protect against breast cancer. The mechanisms by which intake of soy may influence risk of breast cancer are not known. A predominant hypothesis focuses on the potential effects of soy on hormone production and metabolism. The main objective of this soy intervention study was to investigate the relationship between ovarian function in healthy cycling premenopausal women and daily intake of Asian soy foods (tofu, soy milk and soybean peas). The women's hormone levels were compared during the soy intervention with their levels before and after intervention. Twenty women completed this 7-mo study, which consisted of 2 mo of baseline assessment, 3 mo of soyfood supplementation and 2 mo of follow-up assessment. During the entire study period, subjects provided morning urine specimens and blood specimens during specified days of their menstrual cycles. In addition, subjects completed a daily log to record information on menstrual cycle, alcohol intake, exercise pattern, and the amount and types of soy food eaten (during the intervention months only). Soy intervention was associated with a significant reduction in serum luteal estradiol level, but there were no significant changes in follicular phase estradiol, follicular or luteal phase progesterone, sex hormone--binding globulin or menstrual cycle length. Implications of these findings will be discussed.

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.

Background: The four-kallikrein (4K) panel has been demonstrated to improve prediction of aggressive prostate cancer compared with prostate-specific antigen (PSA) among men with moderately elevated PSA levels. However, the development and testing of the 4K panel has been conducted primarily in White men, with limited data in African Americans and no studies in other racial and ethnic groups. Methods: We evaluated the 4K panel in a nested case-control study among African American, Latino, Japanese, Native Hawaiian, and White men in the Multiethnic Cohort. Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 were measured among 1,667 incident prostate cancer cases and 691 controls with PSA ≥2 ng/mL. We evaluated the discriminative ability of the 4K panel within and across all racial/ethnic groups. Results: The 4K panel enhanced discrimination of overall prostate cancer compared with free plus total PSA and total PSA alone (AUC 0.748 vs. 0.711 and 0.669, respectively). Discrimination was further enhanced for Gleason 8+ prostate cancer, aggressive prostate cancer, and death due to prostate cancer, and to a lesser degree for nonaggressive prostate cancer. Improvement of the 4K panel over PSA was observed in each population. Adding a prostate cancer polygenic risk score slightly improved upon the discriminative ability of the 4K panel. Conclusions: The superior discriminative ability of the 4K panel over PSA for overall and aggressive prostate cancer across multiethnic populations indicates the broad clinical applicability of the 4K panel. Impact: Our multiethnic investigation suggests potential for the 4K panel to improve current prostate cancer screening practices. [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., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

Few data exist on the extent to which the differences in breast cancer risk between "racial-ethnic" groups in the United States (US) are "explained" by differences in their distribution of risk factors. We have determined this for African-American (AA), native Hawaiian (NH), Japanese-American (JA), Latina-US-born (L-US), Latina-non-US-born (L-NUS), and white (W) women using prospective incidence data on 88,712 postmenopausal women recruited in 1993-1996. We identified 1,757 incident breast cancer cases through 1999 among these women (1,116 cases after excluding women with a simple hysterectomy or missing risk factor data). Data were available on seven "known" risk factors: ages at menarche and first birth; parity; age at and type of menopause; weight; hormone replacement therapy use; and alcohol consumption. The relative risks (RRs) of breast cancer (with the RR in Ws set to 1.0) for the groups were as follows: W = 1.0; AA = 0.78; NH = 1.33; JA = 0.99; L-US = 0.77; and L-NUS = 0.60. After adjustment for the risk factors, the RRs were as follows: W = 1.0; AA = 0.98; NH = 1.65; JA = 1.11; L-US = 0.95; and L-NUSB = 0.84. The slightly greater risk of the JAs compared with the Ws is in sharp contrast to the very low breast cancer rates that were observed in "traditional" Japanese women and in early Japanese migrants. The adjusted RR of NHs is 65% greater than that of Ws, and that of migrant Latinas is 16% lower than that of Ws. Elucidating the causes of the high rates in NHs is now a major focus of our efforts.