Abstract
The specific mechanism by which low-risk genetic variants confer breast cancer risk is currently unclear, with contradictory evidence on the role of single nucleotide polymorphisms (SNPs) in TOX3/LOC643714 as a breast cancer susceptibility locus. Investigations of this locus using a Chinese population may indicate whether the findings initially identified in a European population are generalizable to other populations, and may provide new insight into the role of genetic variants in the etiology of breast cancer. In this case-control study, 623 Chinese female breast cancer patients and 620 cancer-free controls were recruited to investigate the role of five SNPs in TOX3/LOC643714 (rs8051542, rs12443621, rs3803662, rs4784227, and rs3112612); Linkage disequilibrium (LD) pattern analysis was performed. Additionally, we evaluated how these common SNPs influence the risk of specific types of breast cancer, as defined by estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER2) status. Significant associations with breast cancer risk were observed for rs4784227 and rs8051542 with odds ratios (OR) of 1.31 ((95% confidence intervals (CI), 1.10–1.57)) and 1.26 (95% CI, 1.02–1.56), respectively, per T allele. The T-rs8051542 allele was significantly associated with ER-positive and HER2-negative carriers. No significant association existed between rs12443621, rs3803662, and rs3112612 polymorphisms and risk of breast cancer. Our results support the hypothesis that the applicability of a common susceptibility locus must be confirmed among genetically different populations, which may together explain an appreciable fraction of the genetic etiology of breast cancer.
Highlights
Breast cancer continues to be a major contributor to overall morbidity and mortality among women, accounting for 23% of all cancers in women in 2008 [1], and its incidence continues to increase, in several Asian countries [2]
In unselected breast cancer patients, several genome-wide association studies (GWAS) or studies of specific candidate single nucleotide polymorphisms (SNPs) have revealed a number of novel genetic susceptibility variants and loci, including FGFR2, TOX3/LOC643714, LSP1, MAP3K1, chromosome 8q24, and CASP8, which were independently associated with an increased risk of breast cancer
We provided the supplement data of linkage disequilibrium (LD) structure between the four new SNPs and the five SNPs examined exhibiting moderate to low correlation in the HapMap CHB population, except for rs3112612-rs3104793 with high correlation (Figure S1)
Summary
Breast cancer continues to be a major contributor to overall morbidity and mortality among women, accounting for 23% of all cancers in women in 2008 [1], and its incidence continues to increase, in several Asian countries [2]. In unselected breast cancer patients, several genome-wide association studies (GWAS) or studies of specific candidate single nucleotide polymorphisms (SNPs) have revealed a number of novel genetic susceptibility variants and loci, including FGFR2, TOX3/LOC643714, LSP1, MAP3K1, chromosome 8q24, and CASP8, which were independently associated with an increased risk of breast cancer Most of these studies focused primarily on women of European descent [6,7,8,9,10,11], and replication studies among Asian populations have had mixed success with approximately half of the identified loci [12,13,14,15]. Further investigation of these loci in non-European populations may reveal the generalizability of these initial findings and shed new light onto the biological mechanisms by which genetic variants affect breast cancer etiology
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