Genetic variants in FGFR2 and TNRC9 genes are associated with breast cancer risk in Pakistani women

Mol Med Rep. 2016 Oct;14(4):3443-51. doi: 10.3892/mmr.2016.5633. Epub 2016 Aug 18.

Abstract

Single nucleotide polymorphisms (SNPs) lead to genetic differences in breast cancer (BC) susceptibility among women from different ethnicities. The present study aimed at investigating the involvement of SNPs of three genes, including fibroblast growth factor receptor 2 (FGFR2), trinucleotide-repeat-containing 9 (TNRC9) and mitogen-activated protein kinase kinase kinase 1 (MAP3K1), as risk factors for the development of BC. A case‑control study (90‑100 cases; 90‑100 controls) was performed to evaluate five genetic variants of three genes, including FGFR2 (SNPs: rs1219648, rs2981582), TNRC9 (SNPs: rs8051542, rs3803662) and MAP3K1 (SNP: rs889312) as BC risk factors in Pakistani women. Significant associations were observed between BC risk and two SNPs of FGFR2 [rs2981582 (P=0.005), rs1219648 (P=9.08e‑006)] and one SNP of TNRC9 [rs3803662) (P=0.012)] in Pakistani women. On examining the different interactions of these SNPs with various clinicopathological characteristics, all three associated genetic variants, rs2981582 rs1219648 and rs3803662, exhibited a greater predisposition to sporadic, in comparison to familial, BC. Furthermore, there was an increased effect of BC risk between haplotype combinations of the two SNPs of FGFR2 (rs2981582 and rs1219648) in Pakistani women. The results of the present study suggest that variants of FGFR2 and TNRC9 may contribute to the genetic susceptibility of BC in Pakistani women.

MeSH terms

  • Adult
  • Aged
  • Apoptosis Regulatory Proteins
  • Breast / metabolism
  • Breast / pathology*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • High Mobility Group Proteins
  • Humans
  • MAP Kinase Kinase Kinase 1 / genetics
  • Middle Aged
  • Pakistan / epidemiology
  • Polymorphism, Single Nucleotide*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Receptors, Progesterone / genetics*
  • Trans-Activators
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • High Mobility Group Proteins
  • Receptors, Progesterone
  • TOX3 protein, human
  • Trans-Activators
  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2
  • MAP Kinase Kinase Kinase 1
  • MAP3K1 protein, human

Supplementary concepts

  • Breast Cancer, Familial