rs16260

This candidate gene association study examined 218 postmenopausal women at high breast cancer risk, testing 79 SNPs in steroid metabolism, receptor, cell cycle control, DNA repair, and carcinogen metabolism genes for associations with abnormal breast tissue cytomorphology (RPFNA atypia) as a biomarker for HRT-related breast cancer risk. Key findings: RAD54 Gln929Glu (rs3088074, OR=1.74), TFR Gly142Ser (rs3817672, OR=1.98, p=0.0025), VEGF 3'UTR (rs3025039, OR=2.12), and ACE I/D (rs4646994, OR=0.55) were associated with RPFNA atypia. RAD23B Ala249Val (rs1805329) showed strongest association with worsening cytomorphology on HRT versus off HRT (p=0.0009) and ERCC1 3'UTR (rs3212986) was borderline significant (p=0.0015). Results suggest DNA repair gene polymorphisms may modify breast tissue response to exogenous estrogens.

This comprehensive review examines genetic association studies on prostate cancer, discussing GWASs that have identified over 75 variants associated with PCa risk (as of February 2016), with major susceptibility regions at 8q24, 17q12, 17q24, 10q11, and 19q13. The paper also reviews candidate gene-based approaches targeting genes involved in androgen signaling, carcinogen metabolism, DNA repair, vitamin D signaling, inflammation, angiogenesis, and cellular adhesion, as well as regulatory RNA genes.

This study examined the relationship between 233 colorectal cancer (CRC) risk loci and overall survival in 1,926 patients with advanced CRC from clinical trials. Two SNPs significantly associated with survival under a recessive model were identified: rs117079142 (HR=2.79, 95% CI=1.70-4.58, P=4.7×10⁻⁵) mapping to UTP23/EIF3H, and rs9924886 (HR=1.24, 95% CI=1.12-1.38, P=5.2×10⁻⁵) mapping to CDH1/CDH3. Low CDH1 gene expression in tumors was associated with worse survival (HR=2.18, P=1.8×10⁻³), supporting a prognostic role for CDH1 variants.

This study confirms a strong association between the E-cadherin gene (CDH1) promoter SNP rs16260 and prostate cancer risk in families with positive family history (FH+), with P=0.003 in an independent replication population. The variant A-allele showed increased risk with OR 1.5 for heterozygotes and OR 2.6 for homozygotes compared to CC genotype. A common haplotype carrying rs16260 was also significantly associated with familial PC risk (P=0.004), and family-based transmission tests confirmed over-transmission of rs16260 to affected offspring.

A case-control association study of 1,036 prostate cancer cases and 669 controls from three Swedish population-based studies found that the -160C/A polymorphism in the CDH1 (E-cadherin) gene promoter was significantly associated with hereditary prostate cancer (HPC), with OR = 1.7 (95% CI 1.0–2.7) for CA heterozygotes and OR = 2.6 (95% CI 1.4–4.9) for AA homozygotes, but showed no association with sporadic or familial prostate cancer. The A-allele was identified as a low-penetrance susceptibility variant primarily relevant in hereditary cancer contexts.