Innate Immunity Pathways and Breast Cancer Risk in African American and European-American Women in the Women’s Circle of Health Study (WCHS)

• DOI: 10.1371/journal.pone.0072619
• Publication Date: 2013-08-21T21:06:00Z
• Authors: Zhihong Gong; Lei Quan; Song Yao; Gary Zirpoli; Elisa V. Bandera; Michelle Roberts; Jean-Gabriel Coignet; Citadel Cabasag; Lara Sucheston; Helena Hwang; Gregory Ciupak; Warren Davis; Karen Pawlish; Lina Jandorf; Dana H. Bovbjerg; Christine B. Ambr...; Chi-Chen Hong
• Keywords: Ancestry-informative marker

African American (AA) women are more likely than European (EA) 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 AA and EA women, examined their associations cancer risk within the Women's Circle Health Study (WCHS). In stage I study (864 650 women) we found that genotype frequencies for 35 42 tested SNPs (18 candidate genes) differed between AAs EAs (corroborated by ancestry informative markers). Among premenopausal comparing variant allele carriers non-carriers, reduced was associated CXCL5-rs425535 (OR=0.61, P=0.02), while among there were TNFA-rs1799724 (OR =2.31, P =0.002) CRP-rs1205 (OR=0.54, P=0.01). For postmenopausal IL1B-rs1143627 (OR=1.80, P=0.02) IL1B-rs16944 (OR=1.85, =0.02) significant limited estrogen receptor (ER) positive cancers (OR=2.0, =0.001). However, none retained significance after Bonferroni adjustment multiple testing at level P0.0012 (0.05/42) except ER cancers. a II validation (1,365 1,307 women), extended evaluations four (CCL2-rs4586, CRP-rs1205, CXCL5-rs425535, IL1RN-rs4251961), which yielded similar results. summary, genes involved differ populations, showed differential according menopausal or status. These results suggest adaptations suited ancestral environments may differentially influence women.