RET polymorphisms and haplotypes and risk of differentiated thyroid cancer

Laryngoscope. 2005 Jun;115(6):1035-41. doi: 10.1097/01.MLG.0000162653.22384.10.


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.

Publication types

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

MeSH terms

  • Female
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Oncogene Proteins / genetics*
  • Polymorphism, Genetic*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Thyroid Neoplasms / genetics*


  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases