title: Combinational polymorphisms of seven CXCL12-related genes are protective against breast cancer in Taiwan.
abstract: Many single nucleotide polymorphisms (SNPs) have been found to be associated with breast cancer, but their SNP interactions are seldom addressed. In this study, we focused on the joint effect for SNP combinations of seven CXCL12-related genes involved in major cancer-related pathways. SNP genotyping was determined by PCR-restriction fragment length polymorphism (RFLP) in this study (case = 220, control = 334). Different numbers of combinational SNPs with genotypes called the SNP barcodes from different chromosomes were used to evaluate their joint effect on breast cancer risk. Except for vascular endothelial growth factor (VEGF) rs3025039-CT, none of these SNPs were found to individually contribute to breast cancer risk. However, for two combined SNPs, the proportion of subjects with breast cancer was significantly low in the SNP barcode with CC-GG genotypes in rs2228014-1801157 (CXCR4-CXCL12) compared to those with non-CC-GG genotypes. Similarly, the SNP barcode of rs12812942-rs2228014-rs3025039 (CD4-CXCR4-VEGF) and rs12812942-rs3136685-rs2228014-rs1801157 (CD4- CCR7-CXCR4-CXCL12) with specific genotype patterns (AT-CC-CC and AT-AG-CC-GG) among three and four combinational SNPs were significantly low in breast cancer occurrence. More SNP combinations larger than five SNPs were also addressed, and these showed similar effects. After controlling for age, and comparing their corresponding non-SNP barcodes, the estimated odds ratios for breast cancer ranged between 0.20 and 0.71 for specific SNP barcodes with two to seven SNPs. In conclusion, we have associated the potential combined CXCL12-related SNPs with genotypes that were protective against breast cancer, and that may contribute to identification of a low-risk population for the development of breast cancer.
authors.affiliation: Department of Orthopedic Surgery, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Gau-Tyan
authors.initials: GT
authors.lastname: Lin
authors.forename: Hung-Fu
authors.initials: HF
authors.lastname: Tseng
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Yang
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Hou
authors.forename: Li-Yeh
authors.initials: LY
authors.lastname: Chuang
authors.forename: Hsiao-Ting
authors.initials: HT
authors.lastname: Tai
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Tai
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Cheng
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Wen
authors.forename: Chih-Shan
authors.initials: CS
authors.lastname: Liu
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Huang
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Wang
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000328:Adult; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D013624:Taiwan
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers