A study on genetic variants of Fibroblast growth factor receptor 2 (FGFR2) and the risk of breast cancer from North India

PLoS One. 2014 Oct 21;9(10):e110426. doi: 10.1371/journal.pone.0110426. eCollection 2014.

Abstract

Genome-Wide Association Studies (GWAS) have identified Fibroblast growth factor receptor 2 (FGFR2) as a candidate gene for breast cancer with single nucleotide polymorphisms (SNPs) located in intron 2 region as the susceptibility loci strongly associated with the risk. However, replicate studies have often failed to extrapolate the association to diverse ethnic regions. This hints towards the existing heterogeneity among different populations, arising due to differential linkage disequilibrium (LD) structures and frequencies of SNPs within the associated regions of the genome. It is therefore important to revisit the previously linked candidates in varied population groups to unravel the extent of heterogeneity. In an attempt to investigate the role of FGFR2 polymorphisms in susceptibility to the risk of breast cancer among North Indian women, we genotyped rs2981582, rs1219648, rs2981578 and rs7895676 polymorphisms in 368 breast cancer patients and 484 healthy controls by Polymerase chain reaction-Restriction fragment length polymorphism (PCR-RFLP) assay. We observed a statistically significant association with breast cancer risk for all the four genetic variants (P<0.05). In per-allele model for rs2981582, rs1219648, rs7895676 and in dominant model for rs2981578, association remained significant after bonferroni correction (P<0.0125). On performing stratified analysis, significant correlations with various clinicopathological as well as environmental and lifestyle characteristics were observed. It was evident that rs1219648 and rs2981578 interacted with exogenous hormone use and advanced clinical stage III (after Bonferroni correction, P<0.000694), respectively. Furthermore, combined analysis on these four loci revealed that compared to women with 0-1 risk loci, those with 2-4 risk loci had increased risk (OR = 1.645, 95%CI = 1.152-2.347, P = 0.006). In haplotype analysis, for rs2981578, rs2981582 and rs1219648, risk haplotype (GTG) was associated with a significantly increased risk compared to the common (ACA) haplotype (OR = 1.365, 95% CI = 1.086-1.717, P = 0.008). Our results suggest that intron 2 SNPs of FGFR2 may contribute to genetic susceptibility of breast cancer in North India population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Asian People / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Haplotypes
  • Humans
  • India
  • Linkage Disequilibrium
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Retrospective Studies
  • Risk Factors

Substances

  • Receptor, Fibroblast Growth Factor, Type 2

Associated data

  • Dryad/10.5061/dryad.13F6N

Grants and funding

Financial support for the production of the manuscript was provided by University Grants Commission (UGC) to Department of Biotechnology, Jamia Millia Islamia and Council of Scientific and Industrial Research (CSIR) to S. Siddiqui as scholarship under Grant No. File No. 09/466(0127)/2010-EMR-I. UGC (http://www.ugc.ac.in/) CSIR (http://csirhrdg.res.in/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.