BMC Cancer

BackgroundThe ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes. It is important to determine one\ue2\u20ac\u2122s subtype-specific breast cancer risk when considering chemoprevention. A number of single nucleotide polymorphisms (SNPs), including one in caspase-8 (CASP8), have been previously associated with risk of developing breast cancer. Because caspase-8 is an important protein involved in receptor-mediated apoptosis whose activity is affected by estrogen, we hypothesized that additional SNPs in CASP8 could be associated with breast cancer risk, perhaps in a subtype-specific manner.MethodsTwelve tagging SNPs of CASP8 were analyzed in a nested case control study (1,353 cases and 1,384 controls) of non-Hispanic white women participating in the California Teachers Study. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each SNP using all, estrogen receptor (ER)-positive, ER-negative, human epidermal growth factor receptor 2 (HER2)-positive, and HER2-negative breast cancers as separate outcomes.ResultsSeveral SNPs were associated with all, ER-positive, and HER2-positive breast cancers; however, after correcting for multiple comparisons (i.e., p\ue2\u20ac\u2030<\ue2\u20ac\u20300.0008), only rs2293554 was statistically significantly associated with HER2-positive breast cancer (OR\ue2\u20ac\u2030=\ue2\u20ac\u20301.98, 95 % CI 1.34-2.92, uncorrected p\ue2\u20ac\u2030=\ue2\u20ac\u20300.0005).ConclusionsWhile our results for CASP8 SNPs should be validated in other cohorts with subtype-specific information, we conclude that some SNPs in CASP8 are associated with subtype-specific breast cancer risk. This study contributes to our understanding of CASP8 SNPs and breast cancer risk by subtype.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-2036-9) contains supplementary material, which is available to authorized users.HHSN261201000034C/PHS HHS/United StatesHHSN261201000035C/PHS HHS/United StatesHHSN261201000140C/PHS HHS/United StatesR01 CA77398/CA/NCI NIH HHS/United StatesU58DP003862-01/DP/NCCDPHP CDC HHS/United States2016-01-12T00:00:00Z26758508PMC471101