Combinational polymorphisms of seven CXCL12-related genes are protective against breast cancer in Taiwan.
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.
Lin
Gau-Tyan
GT
Department of Orthopedic Surgery, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tseng
Hung-Fu
HF
Yang
Cheng-Hong
CH
Hou
Ming-Feng
MF
Chuang
Li-Yeh
LY
Tai
Hsiao-Ting
HT
Tai
Ming-Hong
MH
Cheng
Yu-Huei
YH
Wen
Cheng-Hao
CH
Liu
Chih-Shan
CS
Huang
Chih-Jen
CJ
Wang
Chun-Lin
CL
Chang
Hsueh-Wei
HW
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
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D017931:DNA Primers