rs4808075

Genome-wide association study of epithelial ovarian cancer in 755 African ancestry cases and 1,235 controls identified 4 novel loci associated with overall EOC (rs4525119 in AKR1C3 p=4.9×10⁻⁷, rs7643459 in LOC101927394 p=8.4×10⁻⁷, rs4286604 near UGT2A2 p=8.5×10⁻⁷, rs142091544 near WWC1 p=9.4×10⁻⁷) and 6 loci for high-grade serous ovarian carcinoma (rs37792 near FST p=6.0×10⁻⁸, rs57403204 near MAGEC1 p=1.7×10⁻⁷, rs79079890 in LOC105376360 p=3.0×10⁻⁷, rs66459581 near PRPSAP1 p=5.1×10⁻⁷, rs116046250 in GABRG3 p=8.7×10⁻⁷, rs192876988 near GK2 p=9.2×10⁻⁷). The GK2 SNP showed inverse association with EOC in European women (p=0.002) and eQTL evidence for decreased GK2 expression (p=0.004). A European ancestry-derived polygenic risk score showed positive association with EOC in African ancestry women (OR=1.20 per SD, p=4.46×10⁻⁹).

A comprehensive gene-environment interaction study in ovarian cancer examining 28 genome-wide significant variants and 7 environmental risk factors (oral contraceptive use, parity, tubal ligation, breastfeeding, menopausal hormone therapy, BMI, endometriosis) in 9,971 cases and 15,566 controls. The strongest multiplicative interaction identified was between rs13255292 and OCP use (P = 3.48 × 10⁻⁴), with differential protective effects by genotype and duration of use, though no interactions remained significant after multiple testing correction.