Common low-penetrance risk variants associated with breast cancer in Polish women

Abstract

BackgroundBreast cancer is the most common type of cancer and the second leading cause of cancer-death among women in Poland. The known high-risk mutations account for 25% of familial aggregation cases and 5% of total breast cancer predisposition. Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations.MethodsTo verify selected associations with breast cancer susceptibility among Polish women, the replication study was performed, included 1424 women with breast cancer and 1788 healthy persons. Sixteen single-nucleotide polymorphisms (SNPs) were analyzed using TaqMan SNP Genotyping Assays. Allele frequency differences were tested using chi2-test implemented in PLINK v1.07 and Cochran-Armitage trend test was performed using R software.ResultsSignificant differences (Bonferroni corrected p-valuecor ≤ 0.0197) in the frequency of alleles distribution between all cancer and control subjects were observed for four (rs2736098, rs13281615, rs1219648, rs2981582) out of 16 SNPs. The same result was obtained for group of patients without high-risk BRCA1/2 mutations. The rs1219648 (p-valuecor ≤ 6.73E-03) and rs2981582 (p-valuecor ≤ 6.48E-03) SNPs showed significant association with both familial and sporadic cancers. Additionally, rs2736098 (p-valuecor ≤ 0.0234) was associated with only sporadic cancers; also in group without carriers of high-risk mutation. All these associations revealed their significance also in Cochran-Armitage trend test. Opposite to other SNPs, rs2736098 was associated with a decreased risk of breast cancer.ConclusionThe association of four known susceptibility SNPs, representing three individual loci, with breast cancer risk in Polish women was confirmed. One of them (rs2736098) seems to be specific for the Polish population. Due to the population differences in allele frequencies, identification of general genetic risk factors requires sets of association studies conducted on different populations.

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma

“…In fact it has been reported that the GA and/or AA genotypes of rs2736098 are associated with a decreased risk of head and neck (9) and breast (24,25) tumors. However, rs2736098 has been mostly associated with an increased risk for a variety of malignancies especially lung cancer (26).…”

Correlation of FGFR2 rs2981582 polymorphisms with susceptibility to breast cancer: a case-control study in a Chinese population

“…Ledwoń et al. 15 reported a similar result in Polish women (OR = 1.31, 95% CI: 1.17–1.45). In contrast, Bayraktar et al.…”

Lack of Association Between the Matrix Metalloproteinase-2 -1306C>T Polymorphism and Breast Cancer Susceptibility: a Meta-analysis

“…Notably, the -1306 T-allele frequency differs across ethnicities: Saudi (0.10), Chinese (0.12), Brazilian (0.18), Greek (0.18), Australian (0.24), Polish (0.24), Mexican (0.26), Swedish (0.26) (Grieu et al 2004;Zhou et al 2004;Lei et al 2007;Roehe et al 2007;Delgado-Enciso et al 2008;Beeghly-Fadiel et al 2009;Ledwoń et al 2013;Saeed et al 2013a;Zagouri et al 2013). However, when subgroup analysis by ethnicity was performed, we could only find that CC was associated with a significant increase in breast susceptibility among Latin-Americans in the dominant model and the association disappeared in other models.…”

“…A total of 9 case-control studies were eligible Lei et al 2007;Roehe et al 2007;DelgadoEnciso et al 2008;Beeghly-Fadiel et al 2009;Ledwoń et al 2013;Saeed et al 2013a;Slattery et al 2013;Zagouri et al 2013). The flow chart of study selection is shown in Figure 1.…”

“…The total number of sample size of each study ranged from 182 to 7775. For ethnicity distribution, there were 3 studies of Europeans (Lei et al 2007;Ledwoń et al 2013;Zagouri et al 2013), 2 studies of East Asians Beeghly-Fadiel et al 2009), 2 studies of Latin-Americans (Roehe et al 2007;Delgado-Enciso et al 2008), 1 study of Arabians (Saeed et al 2013a) and 1 study of mixed people (Slattery et al 2013). All the studies were reported in full text.…”