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Int J Mol Epidemiol Genet 2013;4(4):218-227

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

Clara Bodelon, Katheleen E Malone, Lisa G Johnson, Mari Malkki, Effie W Petersdorf, Barbara McKnight, Margaret M Madeleine

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Epidemiology,
School of Public Health, University of Washington, Seattle, WA, USA; Division of Clinical Research, Fred Hutchinson Cancer
Research Center, Seattle, WA; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA;
Current affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA

Received October 3, 2013; Accepted November 3, 2013; Epub November 28, 2013; Published December 15, 2013

Abstract: 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. (IJMEG1310001).

Keywords: Breast cancer, chemokines, genetic variation, epidemiology

Address correspondence to: Dr. Clara Bodelon, Division of Cancer Epidemiology and Genetics, National Cancer Institute,
9609 Medical Center Drive, Room 7-E220, Bethesda, MD 20892, USA. Tel: 240-276-7327; Fax: 240-276-7838; E-mail:
clara.bodelon@nih.gov