Updated meta-analysis on HER2 polymorphisms and risk of breast cancer: evidence from 32 studies.

Wei Chen,Heng Yang,Shi-Jun Feng,Wen-Ru Tang,Yun-Lin Wei

doi:10.7314/apjcp.2014.15.22.9643

Abstract

Several studies have been performed to investigate the association of the HER2 Ile655Val polymorphism and breast cancer risk. However, the results were inconsistent. To understand the precise relationship, a meta-analysis was here conducted. A search of PubMed conducted to investigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, of which 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals were used to assess any association. In the overall analysis, the HER2 Ile655Val polymorphism was associated with breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominant genetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model. On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111, 95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asians and Africans in any of the genetic models. In summary, our meta-analysis findings suggest that the HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwide populations with additive and dominant models, but not a recessive model.

Highlights

Breast cancer has a wide distinct range of clinical, pathological and molecular features that makes it a heterogeneous disease (Sorlie et al, 2001)
Information was carefully extracted from each study, the following date of HER2 Ile655Val polymorphism was assessed for Hardy-Weinberg equilibrium in control group using the p text, and a P-value of
The strength of association between HER2 Ile655Val polymorphism and canner was accessed by calculating crude odds ratios (ORs) with 95%CIs

Summary

Introduction

Breast cancer has a wide distinct range of clinical, pathological and molecular features that makes it a heterogeneous disease (Sorlie et al, 2001) It has been progressively increased with estimated 229,060 new diagnoses and 39, 510 deaths per year in the United States, and its incidence is currently increasing in the world (Linos et al, 2008; Ziegler et al, 2008; Siegel et al, 2012). Sequence analysis identified a common genetic variant at codon 655 in the transmembrane coding region of HER2 gene, an Ile-to-Val single-nucleotide polymorphism was found, resulting in the substitution of isoleucine (Ile: ATC) with valine (Val: GTC) (Cooke et al, 2001; Uzan et al, 2009). We conducted a meta-analysis to estimate the possible influence of HER2 Ile655Val polymorphism on the risk of breast cancer

Materials and Methods

Results

Discussion