RET polymorphisms and haplotypes and risk of differentiated thyroid cancer

Objective: To determine whether common (allele frequencies > 5%) single nucleotide polymorphisms located in exons 2, 7, 11, 13, 14, and 15 of the RET proto-oncogene are associated with risk of differentiated thyroid carcinoma (DTC). Study Design: Hospital-based case-control study. Methods: Patients with DTC or benign thyroid disease (BTD) were frequency matched with cancer-free controls on age and sex. Only non-Hispanic whites were included to avoid racial confounding. Polymerase chain reaction-restriction fragment-length polymorphism assays were used for genotyping. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype distributions were estimated using Bayesian analyses. Results: DTC cases and controls had similar rates of tobacco, alcohol, and radiation exposure. The genotype distributions were similar between DTC cases (n = 101) and controls (n = 174) except for RET 7 and RET 14 (P = .003 and P = .047, respectively) and between BTD cases (n = 62) and controls except for RET 14 (borderline; P = .064). Polymorphic allele frequencies were similar between the cases and controls except for RET 14 (borderline; P = .051 and P = .068 for DTC and BTD, respectively). The RET 7 heterozygous polymorphic genotype was associated with a significantly increased risk of DTC after multivariate adjustment (OR = 2.0, 95% CI = 1.2-3.4, P = .012). Compared with the most common haplotype (GGGTCC), no RET haplotype was associated with a significantly increased risk of DTC. Conclusions: Exon 7 (and possibly 14) polymorphism of RET may be associated with increased risk of DTC. However, the sample size is relatively small, and larger investigations are needed.