rs25487

Candidate gene study of 465 HBV-related hepatocellular carcinoma (HCC) patients examined 19 SNPs in Notch pathway receptors (NOTCH1-4) using Sanger sequencing. Four SNPs significantly associated with overall survival: rs1043996 (NOTCH3), rs422951 (NOTCH4), rs520692 (NOTCH4), and rs3830041 (NOTCH4). Notch3 mRNA was significantly elevated in tumors (P<0.0001) and higher expression predicted poorer overall and recurrence-free survival.

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).

This review examines the genetic and epigenetic basis of Tourette Syndrome (TS), a neurodevelopmental disorder with high heritability (0.45-0.77). The paper reviews candidate gene associations including variants in SLITRK1 (rs9593835, rs9546538, rs9531520), DRD2/ANKK1 (rs1800497), ADORA1/ADORA2A (rs2228079, rs5751876), and other dopaminergic genes, along with a large GWAS in 1285 cases and 4964 controls highlighting rs7868992 in COL27A1. The review proposes that epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) may link genetic susceptibility with environmental factors in TS pathogenesis.

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.

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).

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.

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.

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.

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.

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.

This candidate gene association study examined 16 DNA repair gene polymorphisms in 94 patients with metastatic colorectal cancer treated with oxaliplatin-based chemotherapy. The MGMT -535G>T polymorphism (rs1625649) was found to be significantly associated with progression-free survival (PFS) (p=0.076 in univariate analysis), with TT genotype showing improved prognosis compared to GG/GT genotypes (HR=3.137, p=0.005 in multivariate analysis). Several other polymorphisms in DNA repair genes were evaluated for associations with chemotherapy response and survival outcomes.

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 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.

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 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.