rs889312

Genome-wide association study of Ashkenazi Jewish women with familial breast cancer but no BRCA1/2 mutations identified 7 novel SNPs and confirmed 6 known variants. A 7-marker risk model including rs17663555, rs566164, rs11075884, FGFR2 haplotype (rs11200014, rs2981579, rs1078806, rs1219648, rs2420946, rs2981582), rs13387042, rs2046210 (ESR1), and rs3112612 (TOX3) achieved moderate discriminatory accuracy (AUC=0.74; 95% CI: 0.69-0.79) for predicting familial breast cancer risk in this population.

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).

This PhD thesis presents a comprehensive study of microRNA (miRNA) SNPs and their association with breast cancer risk in Australian Caucasian populations. The study identified three key findings: rs2910164 in MIR146A showed significant association (p=0.03 and p=0.00013 in two populations); rs353291 in MIR145 showed significant differences in allele frequencies (p=0.041 and p=0.023); and rs4284505/rs7336610 in the MIR17HG cluster showed significant association with protective effect (OR=0.75, 95% CI: 0.60-0.94, p=0.012).

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.

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.

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.