Association between 5p12 Genomic Markers and Breast Cancer Susceptibility: Evidence from 19 Case-Control Studies

BACKGROUND: The association between polymorphisms on 5p12 and breast cancer (BC) has been widely evaluated since it was first identified through genome-wide association approach; however, the studies have yielded contradictory results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on two wildly studied polymorphisms (rs10941679 and rs4415084) on 5p12. METHODS: Databases including Pubmed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The random-effects model was applied, addressing heterogeneity and publication bias. RESULTS: A total of 19 articles involving 100,083 cases and 163,894 controls were included. An overall random-effects per-allele OR of 1.09 (95% CI: 1.06–1.12; P = 4.5×10(−8)) and 1.09 (95% CI: 1.05–1.12; P = 4.2×10(−7)) was found for the rs10941679 and rs4415084 polymorphism respectively. Significant results were found in Asians and Caucasians when stratified by ethnicity; whereas no significant associations were found among Africans/African-Americans. Similar results were also observed using dominant or recessive genetic models. In addition, we find both rs4415084 and rs10941679 conferred significantly greater risks of ER-positive breast cancer than of ER-negative tumors. CONCLUSIONS: Our findings demonstrated that rs10941679-G allele and rs4415084-T allele might be risk-conferring factors for the development of breast cancer, especially in Caucasians and East-Asians.