Reproduction Abstracts

Prospective studies have reported positive associations between having a history of hyperemesis gravidarum and developing breast cancer in the future, with stronger evidence for HER+ tumors. We investigated whether this relationship may be due to shared biological mechanisms by examining established genetic risk loci for hyperemesis gravidarum in association with breast cancer risk and intrinsic breast cancer subtypes. For this study, we leveraged publicly available breast cancer genetic summary statistics from the Breast Cancer Association Consortium (BCAC, Ahern et al. 2022), which includes genome-wide association data for overall breast cancer (106,571 cases and 95,762 controls) and intrinsic-like subtypes, including Luminal A-like (n = 27,510 cases), Luminal B-like/HER2-negative (n = 6,804 cases), Luminal B-like/HER2-positive (n = 6,511), HER2-postive/non-luminal (n = 2,797) and Triple-negative breast cancer (n = 7,178) among women of European ancestry. The hyperemesis gravidarum-risk variants examined were rs1058587 in GDF15, rs9312688 at IGFBP7 and rs12790159 at PGR. For overall breast cancer, the per allele odds ratio was 0.99 (P = 0.18) for rs1058587, 1.01 (P = 0.07) for rs9312688 and 1.00 (P = 0.40) for rs12790159. No significant associations were observed with any variant and risk of breast cancer intrinsic-like subtypes. In summary, utilizing data from the largest genetic study of breast cancer, we found no significant evidence for shared genetic risk loci between hyperemesis gravidarum and overall breast cancer, HER+ tumors or any intrinsic-like subtype. The suggested association reported between hyperemesis gravidarum and breast cancer risk may be due to exposure to hyperemesis gravidarum rather than shared mechanisms from genetic risk loci.

Keywords: Hyperemesis Gravidarum, Breast cancer, genetic