Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma.

Published

Journal Article

CONTEXT: ATM is critical in response to ionizing radiation-induced DNA damage. OBJECTIVE: Variations in ATM are hypothesized to affect individual susceptibility to thyroid cancer. Our objective was to evaluate the association between ATM polymorphisms and thyroid cancer risk. DESIGN, PARTICIPANTS, AND METHODS: Six ATM single nucleotide polymorphisms (SNP) were genotyped in two independent case-control series including 592 patients with differentiated thyroid carcinoma (DTC) and 885 healthy individuals. An unconditional logistic regression model was applied to calculate odds ratios (OR) and 95% confidence intervals (CI) for each SNP with respect to risk of DTC and the combination effect of SNP on cancer risk. RESULTS: The risk-allele frequencies of all the SNP were similar in the two case-control populations. Under a dominant model of inheritance, the G allele of ATM rs189037 exhibited a protective effect against DTC (adjusted OR = 0.8; 95% CI, 0.6-1.0; P = 0.04), and the G allele of rs1800057 was associated with increased risk of DTC (adjusted OR = 1.9; 95% CI, 1.1-3.1; P = 0.02). A protective haplotype (A-G-C-T-C-A) was associated with decreased risk of DTC in non-Hispanic whites (adjusted OR = 0.2; 95% CI, 0.0-0.8; P = 0.03). A significant dose-response relationship was observed between the total number of risk alleles of ATM and DTC risk (P = 0.01). Carriers of a combination of six to seven and eight to 10 risk alleles were at 30% (adjusted OR = 1.3; 95% CI, 1.0-1.7) and 50% (adjusted OR = 1.5; 95% CI, 1.1-2.1) increased risk of DTC, respectively. CONCLUSION: Individual susceptibility to DTC may be attributable to polymorphisms of ATM, and the associations warrant confirmation in independent studies.

Full Text

Duke Authors

Cited Authors

  • Xu, L; Morari, EC; Wei, Q; Sturgis, EM; Ward, LS

Published Date

  • June 2012

Published In

Volume / Issue

  • 97 / 6

Start / End Page

  • 1913 - 1921

PubMed ID

  • 22438227

Pubmed Central ID

  • 22438227

Electronic International Standard Serial Number (EISSN)

  • 1945-7197

Digital Object Identifier (DOI)

  • 10.1210/jc.2011-3299

Language

  • eng

Conference Location

  • United States