Innate Immunity Pathways and Breast Cancer Risk in African American and European-American Women in the Women’s Circle of Health Study (WCHS)
| Autor: | Lina Jandorf, Christine B. Ambrosone, Karen Pawlish, Citadel J Cabasag, Zhihong Gong, Dana H. Bovbjerg, Gary Zirpoli, Warren Davis, Chi Chen Hong, Lara Sucheston, Michelle Roberts, Helena Hwang, Elisa V. Bandera, Lei Quan, Gregory Ciupak, Jean Gabriel Coignet, Song Yao |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Oncology Candidate gene medicine.medical_specialty lcsh:Medicine Black People Estrogen receptor Breast Neoplasms Single-nucleotide polymorphism Ancestry-informative marker Polymorphism Single Nucleotide White People 03 medical and health sciences 0302 clinical medicine Breast cancer Risk Factors Internal medicine Humans Medicine Allele lcsh:Science 030304 developmental biology 0303 health sciences Multidisciplinary business.industry lcsh:R Case-control study Middle Aged medicine.disease Immunity Innate 3. Good health Genotype frequency Postmenopause Premenopause Case-Control Studies 030220 oncology & carcinogenesis Immunology lcsh:Q Female business Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 8, p e72619 (2013) |
| ISSN: | 1932-6203 |
| Popis: | African American (AA) women are more likely than European American (EA) women to be diagnosed with early, aggressive breast cancer. Possible differences in innate immune pathways (e.g., inflammatory responses) have received little attention as potential mechanisms underlying this disparity. We evaluated distributions of selected genetic variants in innate immune pathways in AA and EA women, and examined their associations with breast cancer risk within the Women's Circle of Health Study (WCHS). In stage I of the study (864 AA and 650 EA women) we found that genotype frequencies for 35 of 42 tested SNPs (18 candidate genes) differed between AAs and EAs (corroborated by ancestry informative markers). Among premenopausal AA women, comparing variant allele carriers to non-carriers, reduced breast cancer risk was associated with CXCL5-rs425535 (OR=0.61, P=0.02), while among EA women, there were associations with TNFA-rs1799724 (OR =2.31, P =0.002) and CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal women, IL1B-rs1143627 (OR=1.80, P=0.02) and IL1B-rs16944 (OR=1.85, P =0.02) were associated with risk among EA women, with significant associations for TNFA-rs1799724 limited to estrogen receptor (ER) positive cancers (OR=2.0, P =0.001). However, none of the SNPs retained significance after Bonferroni adjustment for multiple testing at the level of P0.0012 (0.05/42) except for TNFA-rs1799724 in ER positive cancers. In a stage II validation (1,365 AA and 1,307 EA women), we extended evaluations for four SNPs (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, and IL1RN-rs4251961), which yielded similar results. In summary, distributions of variants in genes involved in innate immune pathways were found to differ between AA and EA populations, and showed differential associations with breast cancer according to menopausal or ER status. These results suggest that immune adaptations suited to ancestral environments may differentially influence breast cancer risk among EA and AA women. |
| Databáze: | OpenAIRE |
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