rs13281615

A meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls) found that the rs6983267 polymorphism on chromosome 8q24 was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95% CI=1.13-1.26; recessive: OR=1.19, 95% CI=1.14-1.25; homozygous: OR=1.31, 95% CI=1.23-1.40). Stratified analyses showed significant associations for colorectal cancer, prostate cancer, and thyroid cancer in Caucasians, and lung cancer in Asians.

Meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls, 170,737 total subjects) examining the association between 8q24 rs6983267 G/T polymorphism and cancer susceptibility. The G risk allele was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95%CI=1.13-1.26; recessive: OR=1.19, 95%CI=1.14-1.25; homozygous: OR=1.31, 95%CI=1.23-1.40). Significant associations were found for colorectal cancer, prostate cancer, thyroid cancer, and lung cancer in ethnicity-stratified analyses.

A hospital-based case-control study in rural and urban India (1,204 cases; 1,212 controls) examined genetic and lifestyle risk factors for breast cancer. Four SNPs in FGFR2 (rs1219648, rs2420946, rs2981575, rs2981582) showed positive associations with breast cancer (ORs 1.32-1.47). Additional SNPs in obesity and metabolic genes (rs374748 in FBN2, rs2922763 in HNF4G, rs2116830 in KCNMA1, rs11121832 in MTHFR, rs16886165 in MAP3K1, rs11594610 in TCF7L2, rs2274459 in MLN) were associated with increased breast cancer risk. Waist-to-hip ratio ≥0.95 showed strong association (OR 3.78; 95% CI 2.92-4.89), and women living first 20 years in rural areas showed protective effect (OR 0.77).

Population-based case-control study of 1,484 breast cancer cases and 1,307 controls examining 13 GWAS-identified SNPs for breast cancer susceptibility. Confirmed associations for 7 SNPs (rs13387042, rs4973768, rs10941679, rs2981582, rs3817198, rs3803662, rs6504950), with women in the highest quintile of a polygenic risk score having 2.2-fold increased breast cancer risk (95% CI: 1.67-2.88) compared to the lowest quintile. No significant interactions were detected between genetic loci and reproductive/menstrual risk factors.

This paper applies a bias correction method for odds ratio estimates from GWAS discovery data, demonstrating that the 'winner's curse' affects initial effect size estimates. The authors applied conditional maximum likelihood estimation to correct bias in GWAS findings from multiple complex diseases (breast cancer, colorectal cancer, lung cancer, prostate cancer, type I and II diabetes) and show that bias-adjusted odds ratios are substantially more consistent with subsequent replication studies, with selection-adjusted confidence intervals providing better uncertainty quantification than uncorrected estimates.

This case-control study examined whether seven breast cancer susceptibility alleles (in FGFR2, TNRC9, MAP3K1, LSP1, and chromosomal regions 8q24 and 2q35) were associated with epithelial ovarian cancer risk. The pooled analysis of 1,383 ovarian cancer cases and 1,804 controls found no significant associations between these variants and ovarian cancer risk, with OR estimates for FGFR2 rs1219648 of 1.06 (95% CI=0.95-1.18) and rs2981582 of 1.04 (95% CI=0.93-1.15), suggesting that breast cancer risk alleles may be specific to breast cancer.

A nested case-control study of 692 invasive endometrial cancer cases and 1,723 controls within the Nurses' Health Study and Women's Health Study investigated whether seven breast cancer risk alleles were also associated with endometrial cancer risk. In contrast to breast cancer, the authors found an inverse association with rs2981582 (FGFR2) and endometrial cancer risk (OR=0.75, 95% CI: 0.60-0.95), and non-significant inverse associations with rs889312 (MAP3K1, OR=0.85) and rs1219648 (FGFR2, OR=0.86). No associations were observed with the other four SNPs, suggesting important biological differences between endometrial and breast cancer despite their shared hormone-related etiology.

This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.

This case-control study investigated 15 SNPs at the 8q24 locus for association with testicular germ cell tumors (TGCT) using 568 cases and 680 controls from the STEED military study. Overall, no significant associations were found between 8q24 SNPs and TGCT risk. However, nonseminomas showed three tentative associations: rs6470494 (OR=1.68 for GG genotype, p=0.04), rs13254738 (OR=1.62 for TT genotype, p=0.07), and an inverse association with rs10505476 (OR=0.67 for CT genotype, p=0.04).

This comprehensive resequence analysis of a 136 kb region of chromosome 8q24 (chr8: 128,473,000-128,609,802) using 454 next-generation sequencing identified 442 novel SNPs and characterized the complete catalog of common variation across regions previously associated with prostate and colorectal cancer risk by GWAS. The study identified 780 common SNPs, with 454 having MAF ≥5%, and determined that 114 tag SNPs are necessary to comprehensively tag the region (r² > 0.8), providing important resources for fine-mapping association signals marked by rs6983267 and rs1447295.