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

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.

Two polymorphisms, rs2046210 and rs3803662, are associated with breast cancer risk in a Vietnamese case-control cohort

“…The two remaining SNPs, rs2046210 and rs3803662, were found to be associated with breast cancer risk in our Vietnamese cohort, with P values less than 0.007 (Table 6). In addition, these results correlate with other association studies of rs2046210 and rs3803662 in Europeans and Asians, especially Japanese, with P values less than 0.03 and the highest OR (95% CI) being 2.16 (1.32-3.59) (Cai et al, 2011;Mizoo et al, 2013;Mazhar et al, 2016;Wang et al, 2016;Hu et al, 2017). Therefore, these two SNPs are likely to increase the risk of breast cancer up to two-fold in Vietnamese women (Tables 7 and 8), as in other ethnic groups.…”

“…Among the genotyped SNPs, five (rs1219648, rs3817198, rs889312, rs10941679 and rs13281615) were found to not show an association with breast cancer risk, but the remaining two (rs2046210 and rs3803662) showed a strong association with the risk of breast cancer in our Vietnamese population cohort. In the literature, five SNPs (rs1219648, rs3817198, rs889312, rs10941679, and rs13281615) were shown to be strongly associated with breast cancer risk in Europeans and Asians (Antoniou et al, 2009;Shan et al, 2012;Wang et al, 2013;Sawyer et al, 2014;Siddiqui et al, 2014;Campa et al, 2015;Ghoussaini et al, 2016;Mazhar et al, 2016;Tang et al, 2016;Zhang et al, 2016;Hein et al, 2017), as well as in populations similar to the Vietnamese, namely Chinese and Taiwanese populations (Liang et al, 2008;Long et al, 2010;Zheng et al, 2010;Kuo et al, 2017). Furthermore, among these populations, these five SNPs have been shown to be associated with an increased risk of breast cancer with the highest OR (95% CI) of 3.06 (1.79-5.25).…”

“…Among them, seven SNPs (rs2046210 in ESR1, rs1219648 in FGFR2, rs3817198 in LSP1, rs3803662 in TNRC9, rs889312 in MAP3K1, rs10941679 in MRPS30 and rs13281615 in PVT-1) have been found to be strongly associated with breast cancer risk in different populations, not only Asian populations (namely Chinese, Japanese, Pakistani and North Indian), but also European (German), African (Tunisian) and Australian populations, with the majority of the P values being much lower than 0.01. Furthermore, the mutated alleles of these SNPs could increase breast cancer risk significantly with odds ratios (ORs) (and 95% confidence interval (CI)) ranging from 1.07 (1.01 -1.14) to 3.06 (1.79 -5.25) (Liang et al, 2008;Antoniou et al, 2009;Cai et al, 2011;Shan et al, 2012;Guan et al, 2014;Lin et al, 2014;Sawyer et al, 2014;Siddiqui et al, 2014;Zhang et al, 2014;Campa et al, 2015;Ghoussaini et al, 2016;He et al, 2016;Mazhar et al, 2016;Hein et al, 2017;Kuo et al, 2017).…”

Genetic Epidemiology of Breast Cancer in Latin America

“…Some studies conducted in Latin America replicated selected loci that were discovered in breast cancer GWAS conducted in samples of European origin: two in Chile and one in Mexico [95,96,116]. These studies tested the association between SNPs in FGFR2 , TOX3 , and MAP3K1 genes and the 2q35 and 8q24 loci, that were replicated in different populations [178,179,180,181,182,183,184]. FGFR2 and MAP3K1 are tyrosine kinases.…”

Genetic determinants of sporadic breast cancer in Sri Lankan women

“…They demonstrated the functional significance of this intronic variant using a combination of luciferase reporter gene assays and electrophoretic mobility shift assays. Similarly, Mazhar et al reported that two intronic variants of FGFR2 [rs2981582 ( P = 0.005), rs1219648 ( P = 9.08e-006)] and a non-coding transcript of CASC16 [rs3803662 ( P = 0.012)] were related to sporadic breast cancer in Pakistani women [ 12 ].…”