rs3212986

This document is a comprehensive collection of ~1,200 cancer-related research abstracts and summaries published in various journals (2013), covering clinical trials, pharmacogenomic studies, and mutation analyses across multiple cancer types including colorectal, breast, lung, lymphoma, and other malignancies. The collection documents associations between genetic variants (SNPs and somatic mutations), gene expression patterns, and cancer treatment outcomes, including studies on KRAS, EGFR, TP53, BRAF, and pharmacogenomic variants like CYP3A4 and UGT1A1.

This functional study examined two ERCC1 SNPs (rs11615 and rs3212986) in 780 healthy Chinese participants and assessed BPDE-DNA adduct levels in cultured lymphocytes from 117 participants as a marker of DNA repair capacity. The minor A allele of rs3212986 was associated with significantly higher BPDE-DNA adduct levels (3,691.3 vs 1,902.5, P<0.01) and haplotype CA showed elevated risk (OR=1.801, 95% CI 1.191-2.724). CAST mRNA expression was reduced in AA carriers. The findings suggest rs3212986 is associated with diminished DNA repair capacity in response to benzo[a]pyrene exposure.

This is a comprehensive journal compilation containing multiple oncology and pharmacogenomics studies published in 2013 across various journals. The collection includes 60+ papers covering cancer treatment outcomes, genetic polymorphisms predicting chemotherapy response and survival, pharmacogenetic variants in drug metabolism and DNA repair genes, and prognostic biomarkers in various cancer types including breast, lung, colorectal, hematologic malignancies, and others. Key findings include associations of XRCC1 variants (rs915927, rs76507, rs2854501, rs2854509, rs3213255) with bladder cancer chemotherapy survival, ABCG2 rs2725264 with lung cancer overall survival (HR 3.22), SLCO1B1 rs4149056 with methotrexate pharmacokinetics, MTHFR rs1801131 with acute lymphoblastic leukemia outcome, and ABCC3/GSTM variants with acute myeloid leukemia survival.

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.

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.

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 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.

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 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.

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.

A systematic review and meta-analysis of 161 published meta-analyses evaluating 344 gene-variant/cancer associations across 99 genes and 18 cancer sites. The authors calculated false-positive report probability (FPRP) values to evaluate the robustness of statistically significant findings (p<0.05). The most noteworthy associations at very low prior probability were GSTM1 null with bladder cancer (OR: 1.5, p=1.9×10-14), NAT2 slow acetylator with bladder cancer (OR: 1.46, p=2.5×10-7), MTHFR C677T with gastric cancer (OR: 1.52, p=4.9×10-8), and GSTM1 null with acute leukemia (OR: 1.20, p=8.6×10-15). Phase II metabolizing enzymes, particularly GSTM1 deletion, showed the most consistent and highly significant associations with cancer risk.

A case-control association study of 141 glioma cases and 108 controls identified polymorphisms in GLTSCR1 (rs1035938, T allele: 40% vs 27%, OR=3.4) and ERCC2 (rs1052555, T allele: 35% vs 18%) associated with oligodendroglioma development. Notably, carriers of the TT genotype at rs1035938 had significantly improved survival (77% at 2 years, 68% at 5 years vs 56% and 34% for other genotypes, P=0.02).