Haplotype analysis on correlation between transcription factor 7-like 2 gene polymorphism and breast cancer risk

Up to now, limited researches focused on the association between transcription factor 7-like 2 gene (TF7L2) gene single nucleotide polymorphisms (SNPs) and breast cancer (BC) risk. The aim of this study was to evaluate the associations between TF7L2 and BC risk in Chinese Han population.

Logistic regression model was used to test the correlation between polymorphisms and BC risk. Strength of association was evaluated by odds ratio (OR) and 95% confidence interval (CI). Generalized multifactor dimensionality reduction (GMDR) was applied to analyze the SNP-SNP and gene-environment interaction.

Logistic regression analysis indicated that the BC risk was obviously higher in carriers of rs1225404 polymorphism C allele than that in TT genotype carriers (TC or CC versus TT), adjusted OR (95%CI) =1.40 (1.09-1.72). Additionally, we also discovered that people with rs7903146- T allele had an obviously higher risk of BC than people with CC allele (CT or TT versus CC), adjusted OR (95%CI) =1.44 (1.09-1.82). GMDR model was used to research the effect of interaction among 4 SNPs and environmental factors on BC risk. We discovered an important two-locus model (p = 0.0100) including rs1225404 and abdominal obesity, suggesting a potential gene-environment correlation between rs1225404 and abdominal obesity. In general, the cross-validation consistency of two-locus model was 10 of 10, and the testing accuracy was 0.632. Compared with subjects with normal waist circumference (WC) value and rs1225404 TT genotype, abdominal obese subjects with rs1225404 TC or CC genotype had the highest BC risk. After covariate adjustment, OR (95%CI) was 2.23 (1.62-2.89). Haplotype analysis indicated that haplotype containing rs1225404-T and rs7903146-C alleles were associated with higher BC risk.

C allele of rs1225404 and T allele of rs7903146, interaction between rs1225404 and abdominal obesity, rs1225404-T and rs7903146-C haplotype were all related to increased BC risk.