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Abstract
BackgroundThe ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes. It is important to determine one’s 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 < 0.0008), only rs2293554 was statistically significantly associated with HER2-positive breast cancer (OR = 1.98, 95 % CI 1.34-2.92, uncorrected p = 0.0005).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.
Highlights
The ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes
Models were adjusted for center, age, family history, BMI, recent physical activity, alcohol consumption, and menopause/hormone therapy (HT) status **Only uncorrected p values
The most recent Breast Cancer Association Consortium (BCAC) paper on CASP8 [26] covered the analysis of 501 typed and 1232 imputed SNPs, and, while some California Teachers Study (CTS) samples were included in the BCAC study, there was only overlap of 57 triple-negative and 49 controls between the BCAC study and our present analysis. rs2293554 was not included on the panel of CASP8 SNPs analyzed in the BCAC paper [26]; using the SNP lookup function on the BCAC website, we found that rs2293554 was not associated with overall, estrogen receptor (ER) +, or ER- breast cancer risk
Summary
The ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes. It is important to determine one’s subtype-specific breast cancer risk when considering chemoprevention. 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. (e.g., tamoxifen and raloxifene) and aromatase inhibitors in reducing the incidence of breast cancer. These drugs were significantly more effective at reducing the incidence of ER-positive breast cancer than ER-negative breast cancer [5,6,7,8,9,10,11,12,13].
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