rs25489

A comprehensive meta-analysis of 50 case-control studies from the Indian subcontinent identified genetic variants modifying lung cancer risk, finding FDR-corrected associations for rs3547/XRCC1 (OR=1.83-2.72) and rs1048943/CYP1A1 (OR=2.07). The rs1048943/CYP1A1 variant showed strongest associations with adenocarcinoma (OR=3.38) and squamous cell carcinoma (OR=3.53) with significant effect modification by smoking status. Global meta-analysis confirmed rs1048943/CYP1A1 association across world populations (OR=1.22, p=0.01).

A study of 559 men with prostate cancer examined associations between circulating carotenoid levels and high-grade prostate cancer risk, finding that higher carotenoid levels (α-carotene OR=0.34, β-carotene OR=0.31, lycopene OR=0.55) were inversely associated with high-grade disease. SNPs in XRCC1 (rs25489), SOD3 (rs699473), and OGG1 (rs1052133) modified these associations, and lycopene levels were associated with lower genomic instability in low-grade tumors.

Population-based case-control study of 601 Connecticut women with non-Hodgkin lymphoma (NHL) and frequency-matched controls examining interactions between DNA repair gene polymorphisms and body mass index. Suggestive gene-BMI interactions were observed for BRCA1 rs799917 (OR=1.7), XRCC1 rs1799782 (OR=1.5), ERCC2 rs13181 (OR=2.0), and other DNA repair genes in modifying NHL risk. After multiple testing correction, significant interactions remained for WRN rs1801195 with T-cell lymphoma (P=0.004) and ERCC2 rs13181 with diffuse large B-cell lymphoma (P=0.002).

A pathway-based candidate gene association study of 218 SNPs in 50 DNA repair genes on non-small-cell lung cancer (NSCLC) survival in 568 Chinese patients. Six SNPs remained significant in multivariate analysis: ATM rs189037 (HR=1.40, p=0.011), MRE11A rs11020802 (HR=1.35, p=0.007), ERCC2 rs1799793 (HR=1.56, p=0.009), MBD4 rs140693 (HR=0.49, p=0.001), XRCC1 rs25487 (HR=1.66, p=0.001), and PMS1 rs5742933 (HR=1.89, p=0.011). In advanced patients treated with platinum-based chemotherapy, ERCC1 rs11615 and XPC rs2228000 were associated with survival.

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

This case-control study of 722 lung cancer cases and 929 controls examined 240 SNPs in DNA repair and cell cycle control pathway genes among smokers. Thirty-eight SNPs were associated with lung cancer risk at P<0.05, with strongest associations in GTF2H4 (rs2074508), LIG1 (rs10500298), PARP1 (rs747658, rs3219073), and XRCC1 (rs1799782, rs3213255). A genetic risk score combining 31 SNPs showed 3.44-fold increased risk in the highest versus lowest quartile.

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 case-control study of 485 HNSCC cases and 549 controls examined the association between XRCC1 polymorphisms (rs1799782, rs25489, rs25487) and head and neck squamous cell carcinoma risk, stratified by HPV16 status and smoking. Among HPV16-seronegative heavy smokers (≥20 pack-years), variant alleles showed increased HNSCC risk (rs25487/399Gln haplotype: OR 1.35, 95% CI 0.97-1.86), while never/light smokers with variant alleles showed reduced risk (OR 0.70, 95% CI 0.42-1.17). No association was found for HPV16-seropositive individuals regardless of smoking status.

A case-control study of 70 Caucasian breast cancer patients examined 8 germline polymorphisms in genes involved in oxidative stress protection, apoptosis, and DNA repair (TP53, NQO1, IL6, TLR4, XRCC1) to predict response to neoadjuvant anthracycline-based chemotherapy. Good pathological response (pCR or residual isolated invasive tumor cells) was significantly more frequent in ER/PR-negative tumors (43.5% vs 10.3% in ER/PR-positive, p=0.006) and G3 tumors (42.4% vs 6.3% in G1/G2, p=0.002). A non-significant trend toward good response was observed in TP53 Arg72Pro carriers (Arg/Arg or Arg/Pro) versus Pro/Pro homozygotes (37.9% or 17.6% vs 0%, p=0.071), and XRCC1 Arg194Trp heterozygotes showed decreased overall survival (HR=6.649, p=0.041).

Case-control study of 1,150 bladder cancer cases and 1,149 controls analyzing 43 SNPs in 12 base excision repair (BER) genes. Significant associations with bladder cancer risk were found for OGG1 rs125701 (OR=0.78, 95% CI 0.63-0.96, decreased risk), PARP1 rs1136410/V762A (OR=1.24, 95% CI 1.02-1.51, increased risk), and POLB rs3136717 (OR=1.30, 95% CI 1.04-1.62, increased risk). Meta-analysis of XRCC1 rs25487 (Q399R) across 7 studies showed no overall association with bladder cancer risk.