Abstract 4621: Polymorphisms in JAK/STAT signaling pathway genes and risk of breast cancer

Background. Impaired function of JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling pathway genes leads to immunodeficiency; genetic variation in this pathway could affect breast cancer risk. Methods. We evaluated associations between genetic polymorphisms (SNPs) in 14 genes in the JAK/STAT pathway (JAK3, STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6, SCOS1, SCOS2, SCOS3, SCOS4, APOBEC and ADAR) and breast cancer risk using data from the OncoArray. As the JAK/STAT pathway interacts with ER and PR, we also examined these associations by breast cancer subtype. We examined a total of 203 genetic variants in 60,106 cases (38,531 ER positive, and 9,363 ER negative) and 46,300 controls. Results. SNP rs738308 in APOBEC was associated with risk of overall breast cancer (P value Conclusion. We found increased breast cancer risk associated with rs738308 in APOBEC, and SNPs in ADAR1, both involved in RNA editing processes. APOBEC has been linked with cancer development and cholesterol control. Increased ADAR expression has been found in 50% of triple negative breast cancers (TNBC), which has been associated with increased recurrence and worse survival. RNA seq analysis showed that ADAR1 is among the top 5% of upregulated genes in relapsed lobular breast cancer. Activation of the JAK2/STAT3 pathway has been associated with TNBC poor prognosis. Our next step is to analyze these genetic variants using the iCOGs dataset which includes 116,587 additional patients and controls. Citation Format: Manuela Gago-Dominguez, Maria E. Martinez, Roger Milne, Marcos Matabuena, Carmen Redondo, Jose Esteban Castelao, Catriona Jamieson. Polymorphisms in JAK/STAT signaling pathway genes and risk of breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4621.