rs2228001

A case-control study of 988 bladder cancer cases and 1,004 controls from Los Angeles and Shanghai examined 632 tagSNPs in 28 DNA repair genes across four pathways. Key findings include associations between POLB rs7832529 (OR=1.5, p=0.003) and bladder cancer risk among Chinese, XPC SNPs (rs2607734, rs2279017, rs2228001) among Chinese males, and OGG1 SNPs among Chinese females. XRCC6 rs2284082 showed significant interaction with smoking (p=0.001).

This study examined PAH-related DNA adduct levels in 111 female never-smokers from Iran, evaluating 21 SNPs in 14 xenobiotic metabolism genes and 12 SNPs in 8 DNA repair genes. DNA adduct levels were significantly lower with NAT2 slow alleles (β=-0.24, p=0.01) and ERCC5 non-risk genotype (β=0.16, p=0.04), but higher with MPO risk alleles (β=0.21, p=0.01). The combination of phase I genes and measured NER capacity explained 17% more variation in adduct levels than environmental exposure alone (r²=0.24 vs 0.07), demonstrating the importance of genetic polymorphisms in PAH metabolism and DNA repair capacity.

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).

In a case-control study of 658 oropharyngeal squamous cell carcinoma (SCCOP) patients, genetic variants in nucleotide excision repair (NER) pathway genes were associated with cancer recurrence risk. In a dominant genetic model, XPC rs2228000 Ala/Val+Val/Val was associated with increased recurrence (HR=1.6, 95% CI 1.1-2.3), while XPD rs1799793 Asp/Asp and XPG rs17655 His/His were associated with decreased recurrence (HR=0.4, 95% CI 0.3-0.6 and HR=0.5, 95% CI 0.4-0.8, respectively), particularly in HPV16/18-positive tumors.

Case-control study of 150 melanoma patients and 150 healthy controls evaluating seven nucleotide excision repair pathway polymorphisms (XPC Lys939Gln and Ala499Val, XPD Lys157Gln/Asp272Asn/Arg751Arg, XPG Asp1104His, XPF Arg415Gln) and cutaneous melanoma susceptibility. None of the polymorphisms showed significant association with melanoma risk in the Iranian population studied.

A case-control study of 139 patients with advanced ovarian cancer found that SNPs in the nucleotide excision repair (NER) pathway genes, particularly XPC and XPF/ERCC4, were associated with platinum chemotherapy response. XPC rs3731108 AG/AA genotype was associated with prolonged progression-free survival (PFS) of 21.3 months vs 13.4 months (HR=0.63, p=0.03), XPC rs1124303 GT/GG genotype with PFS of 22.8 vs 14.9 months (HR=0.47, p=0.03), and XPC-PAT polymorphism with extended PFS (HR=0.56, p=0.01). These XPC associations remained significant after multivariate adjustment for BRCA status and cytoreductive surgery outcome.

This case-control study of 200 Hodgkin disease cases and 220 matched controls examined whether polymorphisms in DNA repair genes (XPD, XPC, XPG, XRCC1, XRCC3) modulate HD risk. The XRCC1 Arg399Gln variant was significantly associated with increased HD risk (OR=1.77, 95% CI 1.16–2.71, p=0.04), and gene-gene interactions between XRCC1 and XRCC3 variants showed even stronger associations (e.g., XRCC1 Arg399Gln + XRCC3 Met241Met: OR=4.13). A cumulative genetic risk score showed significant dose-response association with HD risk (p for trend=0.02).

A case-control study of nucleotide excision repair (NER) pathway genes and lung cancer risk among 113 Latino cases, 255 African American cases, and 579 controls from the San Francisco Bay Area (1998-2003). Among Latinos, ERCC2 haplotype CGA (rs238406, rs11878644, rs6966) showed reduced lung cancer risk (OR=0.65, 95% CI: 0.44-0.97). Among African Americans, ERCC5 rs17655 His/His genotype increased lung cancer risk (OR=1.78, 95% CI: 1.09-2.91), while LIG1 haplotype GGGAA reduced risk (OR=0.61, 95% CI: 0.42-0.88). Multifactor dimensionality reduction identified a 4-factor model including rs171140, rs17655, and rs20581 with 67.4% prediction accuracy for lung cancer (p=0.001) in Latinos.