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).


METHODS
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.
Ho
Tang
T
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-1402, USA.
Li
Guojun
G
Zhao
Chong
C
Wei
Qingyi
Q
Sturgis
Erich M
EM
D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases