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Background: Previous studies investigating relationship between atopic allergic conditions (AACs)—a highly reactive immune state—and prostate cancer (PCa) risk were inconclusive, and few have studied diverse racial/ethnic populations. Methods: We analysed 74,714 men aged ≥45 years at enrollment in Multiethnic Cohort study. Using multivariable Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for self-reported AAC status on PCa outcomes. Results: Through 2017, 8697 incident PCa and 1170 related deaths occurred. Twenty-one percent of men reported a history of AACs. AACs were not associated with incident PCa (HR = 0.98, 95% CI: 0.93–1.03) but were significantly inversely associated with PCa mortality (HR = 0.79, 95% CI: 0.67–0.92). This inverse association was consistently observed across all racial/ethnic groups (HR range: 0.60–0.90). Among men diagnosed with PCa, AACs were inversely associated with PCa-specific death (HR = 0.75, 95% CI: 0.63–0.89). Adjusting for potential confounding effect of PSA screening did not meaningfully change the results. No significant heterogeneity was observed in the effect of AACs on PCa incidence or mortality by Dietary Inflammatory Index. Conclusions: Hyper-allergic conditions were not associated with PCa incidence but were inversely associated with PCa mortality, suggesting a potential role in reducing tumour progression. Further aetiological research is warranted to understand underlying mechanisms. [ABSTRACT FROM AUTHOR]

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]

Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. [ABSTRACT FROM AUTHOR]

Prostate specific antigen (PSA) is widely used as a diagnostic biomarker for prostate cancer (PC). However, due to its low predictive performance, many patients without PC suffer from the harms of unnecessary prostate needle biopsies. The present study aims to evaluate the reproducibility and performance of a genetic risk prediction model in Japanese and estimate its utility as a diagnostic biomarker in a clinical scenario. We created a logistic regression model incorporating 16 SNPs that were significantly associated with PC in a genome-wide association study of Japanese population using 689 cases and 749 male controls. The model was validated by two independent sets of Japanese samples comprising 3,294 cases and 6,281 male controls. The areas under curve (AUC) of the model were 0.679, 0.655, and 0.661 for the samples used to create the model and those used for validation. The AUCs were not significantly altered in samples with PSA 1-10 ng/ml. 24.2% and 9.7% of the patients had odds ratio <0.5 (low risk) or >2 (high risk) in the model. Assuming the overall positive rate of prostate needle biopsies to be 20%, the positive biopsy rates were 10.7% and 42.4% for the low and high genetic risk groups respectively. Our genetic risk prediction model for PC was highly reproducible, and its predictive performance was not influenced by PSA. The model could have a potential to affect clinical decision when it is applied to patients with gray-zone PSA, which should be confirmed in future clinical studies. [ABSTRACT FROM AUTHOR]

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identi ed in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] .1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed signi cant heterogeneity of effect by racial/ethnic group (Pheterogeneity < 0.05), eight were positively associated with risk (OR .1) in at least ve groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations. [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]

Objectives: Since the 1970s incidence rates for esophageal and gastric cardia adenocarcinomas have risen substantially, particularly among white males in the United States. Reasons for the increase of these tumor types are not well understood. We sought to determine the role of smoking, alcohol use, and body size characteristics in the etiology of esophageal, gastric cardia, and distal gastric adenocarcinomas.Materials and Methods: A population-based case-control study that included Whites, African-Americans, Latinos and Asian-Americans diagnosed with incident esophageal (n = 222), gastric cardia (n = 277), and distal gastric adenocarcinomas (n = 443), and 1356 control subjects was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs), as an estimate of the relative risk, and corresponding 95% confidence intervals (CIs) for the three tumor types of interest.Results: After adjustment for age, gender, race, birthplace, and education, current cigarette smoking was a significant risk factor for all tumor types; the association was strongest for esophageal adenocarcinomas (OR = 2.80, 95% CI = 1.8-4.3), intermediate for gastric cardia adenocarcinomas (OR = 2.12, 95% CI = 1.5-3.1), and weaker for distal gastric adenocarcinomas (OR= 1.50, 95% CI = 1.1-2.1). For esophageal adenocarcinomas only, cigarette smoking had a long-lasting deleterious effect, even 20 years after smoking cessation. Alcohol use was not associated with an increased risk of these tumor types. Risks of esophageal and gastric cardia adenocarcinomas also increased statistically significantly in a dose-dependent manner with increasing body mass index measured at ages 20 and 40 years and recently. The positive associations with smoking and body mass index were generally consistent when evaluated separately for Whites, non-Whites, males, and females.Conclusions: Cigarette smoking and high body mass index are significant, independent risk factors for esophageal and gastric cardia adenocarcinomas. Studies designed to understand the mechanisms whereby smoking and high body mass influence these tumor types are needed. [ABSTRACT FROM AUTHOR]