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

Thyroid. 2012 Jan;22(1):35-43. doi: 10.1089/thy.2011.0117. Epub 2011 Dec 2.

Abstract

Background: 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).

Methods: 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.

Results: 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).

Conclusion: BRCA1 genetic polymorphisms may play a role in DTC risk, while the possible associations warrant confirmation in independent studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / genetics*
  • Adenocarcinoma, Follicular / pathology
  • Adenoma, Oxyphilic
  • Adult
  • Alleles
  • Carcinoma
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Case-Control Studies
  • Female
  • Genes, BRCA1*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Supplementary concepts

  • Thyroid cancer, Hurthle cell