GermLine Variation in Superoxide Dismutase-2 (SOD2) and Survival Outcomes After Radiation Therapy for Prostate Cancer: Results of a Test and Validation Set Analysis

© 2015 Elsevier Inc. Background: Genetic variants in antioxidant pathways might decrease the efficacy of radiation therapy (RT) by suppressing the generation of reactive oxygen species. We studied the association between single nucleotide polymorphisms (S

A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.

BACKGROUND: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer). METHODS: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian. RESULTS: The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years. CONCLUSIONS: Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men

Ecological Contexts in Adolescent Pregnancy: The Role of Individual, Sociodemographic, Familial and Relational Variables in Understanding Risk of Occurrence and Adjustment Patterns

Adolescent pregnancy appears today as an intricate tapestry where different dimensions interact. In our study we examined the associations between individual, sociodemographic, familial, and relational variables and their impact in the occurrence of pregnancy and adolescents’ adjustment to it. Participants were Portuguese pregnant and non-pregnant adolescents (N = 833). Ecological contexts were characterized, and individual and relational adjustment (depressive symptoms and quality of life; perceived quality of relationship with significant others – parents, romantic partner and friends) were evaluated. Differences between the ecologies of adolescents in both groups were identified. Familial and relational variables were significantly associated with both the risk of pregnancy and more difficulties in adjustment. Implications for preventive intervention are discussed