Association of transcription factor 7-like 2 gene polymorphisms with breast cancer risk in northwest Chinese women.

Weili Min,Zhijun Dai,Xiaobin Ma,Xijing Wang,Tianbo Jin,Qingyong Ma,Shanli Li,Zhuoqing Gong,Kang Liu,Huafeng Kang,Shuai Lin,Meng Wang,Yi Zheng,Ye Lu,Xinghan Liu,Cong Dai

doi:10.18632/oncotarget.12591

Abstract

Genetic variations in transcription factor 7-like 2 (TCF7L2) are associated with cancer risk. This study was conducted to establish the relationship between TCF7L2 polymorphisms (rs1225404, rs7003146, and rs7903146) and clinical features and risk of breast cancer in Northwest Chinese Han women. In this study, three polymorphisms of TCF7L2 (rs1225404, rs7003146, and rs7903146) were genotyped in 458 patients with breast cancer and 500 healthy controls using the Sequenom MassARRAY-iPLEX system. We evaluated the associations between the polymorphisms and breast cancer using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The C allele of rs1225404 was associated with increased breast cancer risk (OR = 1.58, P = 0.0004, PC= 0.0012), whereas the G allele of rs7003146 was associated with decreased breast cancer risk (OR = 0.71, P = 0.01, PC= 0.03). Furthermore, the rs1225404 polymorphism positively correlated with negative progesterone receptor status. A positive correlation with positive estrogen receptor (ER) status was observed for the rs7003146 polymorphism. Our results suggest that TCF7L2 polymorphisms rs1225404 and rs7003146, but not rs7903146, may affect breast cancer risk in Northwest Chinese women. Additionally, the tag polymorphisms in TCF7L2 are associated with the clinical features of breast cancer, which may provide us novel insight into the pathogenesis of breast cancer.

Highlights

Breast cancer (BC) accounts for the largest proportion of women cancer globally, and has a significant tendency to onset among younger people [1]
We evaluated the associations between the polymorphisms and breast cancer using odds ratios (ORs) and corresponding 95% confidence intervals
Our results suggest that transcription factor 7-like 2 (TCF7L2) polymorphisms rs1225404 and rs7003146, but not rs7903146, may affect breast cancer risk in Northwest Chinese women

Summary

INTRODUCTION

Breast cancer (BC) accounts for the largest proportion of women cancer globally, and has a significant tendency to onset among younger people [1]. B-catenin binds to TCF7L2 in the nucleus, which activates its transcription factor activity This results in the expression of some specific genes such as the cyclin D1, MCP-1, and c-myc oncogenes, which is a common feature in human cancers [5,6,7,8]. The rs7003146 (G/T) polymorphism significantly correlated with reduced BC risk in Han nationality of China [18] and the rs1225404 (GA/AA genotype) may be an anti-breast cancer factor in Hispanic populations [15]. Pervious studies reported the inconsistent conclusions about the association between the three polymorphisms (rs1225404, rs7003146, and rs7903146) and breast cancer in different ethnicities, so we performed this study to confirm the effect of the TCF7L2 polymorphisms to BC risk, we genotyped all participants from a Chinese Han population in Northwest China for the three important SNPs, rs1225404, rs7003146, and rs7903146

RESULTS

DISCUSSION

MATERIALS AND METHODS