Common sequence variants in chemokine-related genes and risk of breast cancer in post-menopausal women

[摘要] Chemokines are small molecules that when secreted by tissues under pathological conditions such as inflammation are believed to be involved in carcinogenesis. Recent reports have found that the genetic variation in chemokine encoding genes are associated with risk of breast cancer. Methods: Using data from a population-based case-control study of 845 invasive breast cases and 807 controls, we genotyped 34 single nucleotide polymorphisms (SNPs) in 8 chemokine candidate genes (CCL3, CCL4, CCL5, CCL20, CCR5, CCR6, CXCL12 and CXCR4). Associations with breast cancer were computed for individual SNPs, groups of SNPs within genes, and in a gene-set analysis. We also performed a meta-analysis of CXCL12 rs1801157 and a haplotype analysis for two SNPs: CXCR4 rs2228014 and CXCL12 rs1801157. Results: We found no significant associations between the risk of breast cancer and any individual SNPs, single genes, or combined gene sets. Some individual variants were marginally associated with some histologic subtypes, but these associations were not significant after adjustment for multiple comparisons. In the meta-analysis of five studies of European ancestry, CXCL12 rs1801157 was marginally associated with breast cancer risk (OR=1.14, 95% CI: 1.00, 1.30). Conclusions: Our findings suggest that genetic variants in the 8 candidate genes coding for chemotactic cytokines have little influence in the risk of breast cancer in postmenopausal women. Additional examination of the relationship between CXCL12 rs1801157 and breast cancer risk is warranted.

[学科分类] 流行病学

[关键词] Breast cancer;chemokines;genetic variation;epidemiology