Patterns of Associations with Epidemiologic Factors by High-Grade Serous Ovarian Cancer Gene Expression Subtypes.
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Collin Lindsay J, Cushing-Haugen Kara L, Terry Kathryn L, Goode Ellen L, Wu Anna H, Harris Holly R, Sasamoto Naoko, Cramer Daniel W, Modugno Francesmary, Elishaev Esther, Fu Zhuxuan, Moysich Kirsten B, Fasching Peter A, Pearce Celeste Leigh, Menon Usha, Gentry-Maharaj Aleksandra, Gayther Simon A, Wentzensen Nicolas, Goodman Marc T, George Joshy, Talhouk Aline, Anglesio Michael S, Ramus Susan J, Bowtell David D L, Tworoger Shelley S, Schildkraut Joellen M, Webb Penelope M, Doherty Jennifer A
Аннотация
METHODS: We pooled data from 11 case-control studies with epidemiologic and tumor gene expression data from custom NanoString CodeSets developed through a collaboration within the Ovarian Tumor Tissue Analysis consortium. The PrOTYPE-validated NanoString-based 55-gene classifier was used to assign HGSC gene expression subtypes. We examined associations between epidemiologic factors and HGSC subtypes in 2,070 cases and 16,633 controls using multivariable-adjusted polytomous regression models.
RESULTS: Among the 2,070 HGSC cases, 556 (27%) were classified as C1.MES, 340 (16%) as C5.PRO, 538 (26%) as C2.IMM, and 636 (31%) as C4.DIF. The key factors, including oral contraceptive use, parity, breastfeeding, and family history of ovarian cancer, were similarly associated with all subtypes. Heterogeneity was observed for several factors. Former smoking [OR = 1.25; 95% confidence interval (CI) = 1.03, 1.51] and genital powder use (OR = 1.42; 95% CI = 1.08, 1.86) were uniquely associated with C2.IMM. History of endometriosis was associated with C5.PRO (OR = 1.46; 95% CI = 0.98, 2.16) and C4.DIF (OR = 1.27; 95% CI = 0.94, 1.71) only. Family history of breast cancer (OR = 1.44; 95% CI = 1.16, 1.78) and current smoking (OR = 1.40; 95% CI = 1.11, 1.76) were associated with C4.DIF only.
CONCLUSIONS: This study observed heterogeneous associations of epidemiologic and modifiable factors with HGSC molecular subtypes.
IMPACT: The different patterns of associations may provide key information about the etiology of the four subtypes.