Genetic variants in EBV reactivation-related genes and the risk and survival of breast cancer

Tumor susceptibility gene 101 (TSG101) and activating transcription factor 2 (ATF2) have been suggested to involve in the reactivation of EBV which has implications in the development and progression of breast cancer. Therefore, the polymorphisms of TSG101 and ATF2 may associate with breast cancer risk and prognosis. A case-control study with 1551 breast cancer cases and 1605 age-matched controls were conducted in Guangzhou, China. We have also successfully followed up 1168 cases until December 31, 2014. The variant allele of TSG101 rs2292179 was associated with a non-significant reduced risk of breast cancer, particularly among women with BMI < 24 (kg/m²) (P for interaction <0.05). For ATF2 rs3845744, the variant allele was also associated with a significantly reduced breast cancer risk [odds ratio (OR) (95 % confidence interval (CI)) 0.86 (0.74∼1.00)], and the association occurred among only postmenopausal women [OR (95 % CI) 0.69 (0.54∼0.88)] (P for interaction <0.05). Breast cancer risk was further reduced with the increasing numbers of the variant G alleles of the two polymorphisms (P for trend <0.05). We did not find an overall association of the two loci with breast cancer prognosis, while the hazard ratios of the two loci (AG/GG vs. AA) were significantly higher among postmenopausal women than premenopausal women (P = 0.046, 0.016 for TSG101 rs2292179 and ATF2 rs3845744, respectively). In summary, the variant alleles of TSG101 rs2292179 and ATF2 rs3845744 were associated with a reduced risk of breast cancer, particularly for subjects with BMI <24 (kg/m²) and postmenopausal women, respectively. The two SNPs and menopausal status may have a significant interaction on breast cancer progression.