Novel polymorphisms in caspase-8 are associated with breast cancer risk in the California Teachers Study.

Abstract

BACKGROUND:

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. 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.

METHODS:

Twelve 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.

RESULTS:

Several 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).

CONCLUSIONS:

While 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.

• Authors: Hannah Lui Park, Argyrios Ziogas, Jenny Chang, Bhumi Desai, Leona Bessonova, Chad Garner, Eunjung Lee, Susan L Neuhausen, Sophia S Wang, Huiyan Ma, Jessica Clague, Peggy Reynolds, James V Lacey Jr, Leslie Bernstein, Hoda Anton-Culver
• Journal: BMC cancer (BMC Cancer) Vol. 16 Pg. 14 (Jan 12 2016) ISSN: 1471-2407 [Electronic] England
• PMID: 26758508 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Receptors, Estrogen
• Receptors, Progesterone
• ERBB2 protein, human
• Receptor, ErbB-2
• Caspase 8

Topics

• Adult
• Breast Neoplasms (genetics, pathology)
• California
• Caspase 8 (genetics)
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genotype
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptor, ErbB-2 (genetics)
• Receptors, Estrogen (genetics)
• Receptors, Progesterone (genetics)
• Risk Factors