rs13181

A prospective study of 91 primary central nervous system lymphoma (PCNSL) patients examined genetic polymorphisms in DNA repair, one-carbon metabolism, and metabolism genes as prognostic markers. ABCB1 rs1045642 was identified as an independent prognostic factor, with the CC genotype significantly associated with shorter progression-free survival (PFS: 16 months CC vs. 27 months TT/CT, HR=1.9, P=0.036) and higher risk of disease progression compared to T allele carriers.

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 candidate gene association study screening 1,421 SNPs in 407 cancer-related genes identified two novel susceptibility loci for childhood B-precursor acute lymphoblastic leukemia: rs6966 in PPP1R13L/ERCC2 region (OR=3.74, 95% CI 2.31-6.04, p=4.55×10⁻⁹) and rs414580 in MSR1 (OR=3.93, 95% CI 2.31-6.69, p=6.09×10⁻⁸). A third SNP, rs11762213 in MET, showed borderline significance (p=2.97×10⁻²).

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.

Genome-wide association study identifying genetic polymorphisms associated with severe oxaliplatin-induced chronic peripheral neuropathy (OXCPN) in colon cancer patients. Discovery analysis of 96 patients and validation in 247 patients identified 9 SNPs in 8 genes with nominal replication (P < 0.05), with the strongest association at rs10486003 in TAC1 (P = 4.84 × 10⁻⁷, OR = 0.32). A prediction model using 5 SNPs (rs10486003, rs2338, rs830884, rs843748, rs797519) achieved 72.8% accuracy in model development and 75.9% in model evaluation.

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 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 case-control association study evaluated 23 genetic sequence variants in 17 genes across DNA repair, cell cycle, and other pathways in 531 stage I-II radiation-treated head and neck cancer (HNC) patients to identify associations with secondary primary cancers (SPCs). Among the variants tested, the DNMT3B C149T variant (rs2424913) showed a strong significant association with SPC development, with adjusted hazard ratios of 2.23 (95% CI, 1.32-3.78; P = .003) for TT versus CC genotype and 1.49 (95% CI, 1.15-1.95; P = .003) per T allele. A haplotype cluster of 5 DNMT3B variants in strong linkage disequilibrium also showed significant associations (P < .003), suggesting aberrant DNA methylation is an important modulator of field cancerization in HNC.

A case-control study of 150 chronic myeloid leukemia (CML) patients and 150 healthy controls found significant associations between GSTT1 null (OR=3.39, p<0.001), GSTM1 null (OR=2.9, p<0.001), and XPD Lys751Gln polymorphisms (rs13181 Lys/Lys OR=1.43 p=0.027; Gln/Gln OR=2.98 p=0.013) and increased CML risk. Combined GSTT1/GSTM1 null with XPD Lys/Lys showed the strongest association (OR=9.5, p=0.034).

A study of 348 multiple myeloma patients examined associations between SNPs in chromosome 19q13.3 (specifically in RAI and CD3EAP genes) and treatment outcomes following high-dose chemotherapy with stem cell support. Polymorphisms RAI-intron1-1 (rs4572514) and CD3EAP G-21A (rs967591) were significantly associated with prolonged time-to-treatment failure (p=0.003) and overall survival (p=0.02). Combination analyses with the NFKB1 promoter polymorphism suggested potential functional effects related to NF-κB pathway involvement.

Nested case-control study of 859 breast cancer cases and 1,083 controls in US radiologic technologists examining nucleotide excision repair gene polymorphisms and ionizing radiation-related breast cancer risk. ERCC5 rs17655 (C allele) showed borderline main effect (OR=1.3 for CC, p-trend=0.08) and possible gene-radiation interaction (EOR/Gy=5.9 for carriers vs 1.0 for non-carriers, p=0.10). ERCC2 rs13181 significantly modified radiation dose effects (EOR/Gy=9.1 for AA vs 0.6 for AC/CC carriers, p=0.01).

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.