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Association of BRCA1 functional single nucleotide polymorphisms with risk of differentiated thyroid carcinoma.

ABSTRACT: Breast cancer 1, early onset (BRCA1) is a vital DNA repair gene, and the single nucleotide polymorphisms (SNPs) of this gene have been studied in diverse cancer types. In this study, we investigated the association between eight common BRCA1 functional SNPs and the risk of differentiated thyroid carcinoma (DTC).This cancer center-based case-control study included 303 DTC cases and 511 controls. A polymerase chain reaction-based restriction fragment length polymorphism assay was performed for genotyping. Unconditional logistical regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) in single-SNP analysis and haplotype analysis.A decreased risk of DTC was found for the A1988G heterozygous AG genotype (adjusted OR=0.63, 95% CI: 0.45-0.87, Bonferroni-adjusted p-value=0.036). AATAATA and ATAA haplotypes that carry C33420T variant allele were associated with reduced papillary thyroid cancer risk (adjusted OR=0.52, 95% CI: 0.33-0.84; adjusted OR=0.62, 95% CI: 0.40-0.95, respectively). Also, having a combination of ?3 favorable genotypes was associated with a DTC risk reduction (adjusted OR=0.69, 95% CI: 0.50-0.95). The A31875G AG/GG genotype was associated with a 69% reduced risk of multifocal primary tumor in DTC patients (adjusted OR=0.31, 95% CI: 0.12-0.81).BRCA1 genetic polymorphisms may play a role in DTC risk, while the possible associations warrant confirmation in independent studies.

SUBMITTER: Xu L

PROVIDER: S-EPMC3263304 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Association of BRCA1 functional single nucleotide polymorphisms with risk of differentiated thyroid carcinoma.

Xu Li L Doan Phi C PC Wei Qingyi Q Liu Yanhong Y Li Guojun G Sturgis Erich M EM

Thyroid : official journal of the American Thyroid Association 20111202 1

<h4>Background</h4>Breast cancer 1, early onset (BRCA1) is a vital DNA repair gene, and the single nucleotide polymorphisms (SNPs) of this gene have been studied in diverse cancer types. In this study, we investigated the association between eight common BRCA1 functional SNPs and the risk of differentiated thyroid carcinoma (DTC).<h4>Methods</h4>This cancer center-based case-control study included 303 DTC cases and 511 controls. A polymerase chain reaction-based restriction fragment length polym ...[more]

PMID: 22136207

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Project description:Thyroid cancer (TC) is the most common endocrine malignancy and its incidence continues to rise worldwide. Ionizing radiation exposure is the best established etiological factor. Heritability is high; however, despite valuable contribution from recent genome-wide association studies, the current understanding of genetic susceptibility to TC remains limited. Several studies suggest that altered function or expression of the DNA mismatch repair (MMR) system may contribute to TC pathogenesis. Therefore, the present study aimed to evaluate the potential role of a panel of MMR single nucleotide polymorphisms (SNPs) on the individual susceptibility to well-differentiated TC (DTC). A case-control study was performed involving 106 DTC patients and 212 age- and gender-matched controls, who were all Caucasian Portuguese. Six SNPs present in distinct MMR genes (MLH1 rs1799977, MSH3 rs26279, MSH4 rs5745325, PMS1 rs5742933, MLH3 rs175080 and MSH6 rs1042821) were genotyped through TaqMan® assays and genotype-associated risk estimates were calculated. An increased risk was observed in MSH6 rs1042821 variant homozygotes [adjusted odds ratio (OR)=3.42, 95% CI: 1.04-11.24, P=0.04, under the co-dominant model; adjusted OR=3.84, 95% CI: 1.18-12.44, P=0.03, under the recessive model]. The association was especially evident for the follicular histotype and female sex. The association was also apparent when MSH6 was analysed in combination with other MMR SNPs such as MSH3 rs26279. Interestingly, two other SNP combinations, both containing the MSH6 heterozygous genotype, were associated with a risk reduction, suggesting a protective effect for these genotype combinations. These data support the idea that MMR SNPs such as MSH6 rs1042821, alone or in combination, may contribute to DTC susceptibility. This is coherent with the limited evidence available. Nevertheless, further studies are needed to validate these findings and to establish the usefulness of these SNPs as genetic susceptibility biomarkers for DTC so that, in the near future, cancer prevention policies may be optimized under a personalized medicine perspective.

Dataset Information

Association of BRCA1 functional single nucleotide polymorphisms with risk of differentiated thyroid carcinoma.

Publications

Association of BRCA1 functional single nucleotide polymorphisms with risk of differentiated thyroid carcinoma.

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