Abstract 2789: Associations between insertional polymorphisms of human endogenous retrovirus K113 and K115 and breast cancer risk in African American and European American women

Background: Human endogenous retroviruses (HERVs) are remnants of ancient virus infection. The majority of them are disabled due to mutation and/or deletion. However, HERV K113 and K115 have been shown to have full-length insertion in human genome and retain the ability to encode functional virus proteins in some individuals. Considering the potential role of HERVs in carcinogenesis and a high genetic homology between HERV K and mouse mammary tumor virus, the study is designed to investigate the distribution of HERV K113 and K115 in African American (AA) and European American (EA) women, and their association with breast cancer risk. Methods: Built on a funded multi-center case-control study, the Women9s Circle of Health Study, the study included 1242 cases (608 AA and 634 EA) and 1422 controls (783 AA and 639 EA). PCR followed by fragment analysis was used for insertional polymorphism assay. For each HERV, three PCRs were performed to determine whether the insertion is partial or full length. Indeed, a subset of individuals showed insertion of long terminal repeat (LTR) of HERV, instead of whole virus insertion. The distribution of insertional polymorphisms was compared between AA and EA as well as between cases and controls. Logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI) with adjustment for age at diagnosis and proportion of European ancestry. Results: For both K113 and K115, with or without including LTR insertion, the distribution was significantly different between AA and EA women. A two-fold higher prevalence of HERVs was observed in AA women, showing 51.5% of individuals with at least one copy of either K113 or K115 compared to 23.3% in EA women among controls. The prevalence of HERVs was inversely associated with proportions of European ancestry, showing a decrease from averagely 66% European ancestry in individuals without insertion to 42.9%, 23.2%, 13.3% with one, two, or more insertions of HERV K113 or K115, respectively. Between cases and controls, the prevalence of K113 was slightly higher in controls, but not for K115. Furthermore, both K113 and K115 insertion were significantly associated with the reduced risk of breast cancer in both AA and EA women. Near 50% reduction of breast cancer risk was observed in AA and EA women with homozygous insertion of K113 (combined OR, 0.45; 95% CI, 0.25-0.80). A trend of a reduction in breast cancer risk with an increase of copy number of HERV K insertion was observed in both AA and EA women. However, there was no association with breast cancer subtypes. Conclusion: This is the first study to document the prevalence of HERV K113 and K115 in AA and EA population, and to report an inverse association with breast cancer risk. Validation of the findings in a relatively large study is warranted in the future. Funded by 5R03CA156645, K07CA148888, P01151135, and R01CA100598. Citation Format: Li Tang, Steven R. Gregory, David Tritchler, Gary R. Zirpoli, Song Yao, Warren Davis, Gregory L. Ciupak, Yasmin Thanavala, Elisa V. Bandera, Christine B. Ambrosone. Associations between insertional polymorphisms of human endogenous retrovirus K113 and K115 and breast cancer risk in African American and European American women. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2789. doi:10.1158/1538-7445.AM2015-2789