Abstract
Genome-wide association studies have identified SNP rs11249433 at chromosome 1p11 as a new breast cancer (BC) susceptibility locus in populations of European descent. Since then, the relationship between 1p11- rs11249433 and breast cancer has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 15 studies involving a total of 90,154 cases and 137,238 controls for 1p11-rs11249433 polymorphism to evaluate its effect on genetic susceptibility for breast cancer. An overall random effects odds ratio of 1.09 (95% CI: 1.06-1.12, P<10-5) was found for rs11249433-G variant. Significant results were also observed for heterozygous (OR=1.09, 95% CI: 1.05-1.12, P<10-5) and homozygote (OR=1.14, 95% CI: 1.08-1.21, P<10-5). There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant associations were found among Caucasians. However, no significant associations were detected among East Asian and African populations. In addition, we found that rs11249433 polymorphism on 1p11 confer risk, exclusively for ER-positive tumors with per-allele OR of 1.13 (95% CI: 1.08-1.18; P <10-5) compared to ER-negative tumors of 1.01 (95% CI: 0.98-1.04; P=0.49). Similar results were also observed when stratified by PR status. Our findings demonstrated that rs11249433-G allele is a risk-conferring factor for the development of breast cancer, especially in Caucasians.
Highlights
Breast cancer (BC) is one of the most common malignancies among women worldwide [1]
Articles were included in this meta-analysis if they (1) examined the hypothesis that 1p11-rs11249433 polymorphism was associated with breast cancer risk, (2) followed a casecontrol or cohort study design, (3) identified breast cancer cases histologically or pathologically, and (4) provided sufficient information on genotype/allele counts between cases and controls to estimate the odds ratio (OR) and the corresponding 95% confidence interval
A total of 15 studies with 90,154 cancer cases and 137,238 controls were retrieved based on the search criteria for BC susceptibility related to the 1p11-rs11249433 polymorphism [13,20,21,22,23,24,25,26,27,28,29,30,31,32,33]
Summary
Breast cancer (BC) is one of the most common malignancies among women worldwide [1]. Epidemiologic investigation of breast cancer has identified a number of environmental and lifestyle risk factors [2]. Only a few risk genes have been identified These include rare, high-penetrance germline mutations segregating in high-risk pedigrees, notably in the BRCA1 and BRCA2 genes [5,6] and a handful of rare susceptibility variants with lower penetrance identified in DNA repair and apoptosis genes [7,8,9,10,11]. These genes account for less than 5% of overall breast cancer patients and most of the risk is likely to be attributable to more low-penetrance genetic variants [12]. To help clarify the inconsistent findings, we conducted a comprehensive meta-analysis to quantify the overall risk of 1p11-rs11249433 polymorphism on developing breast cancer
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