WDR3 gene haplotype is associated with thyroid cancer risk in a Spanish population.
BACKGROUND
A member of the genes encoding WD-repeat proteins, the WDR3 gene, maps in the 1p12 region. This region was shown to be associated with thyroid cancer susceptibility in a previous work. In this study we aim to evaluate the contribution of WDR3 to thyroid cancer risk.


METHODS
A case-control association study was performed in a total of 402 patients and 479 control subjects from a Spanish population. In the initial phase of the study, 10 single-nucleotide polymorphisms covering the WDR3 region were genotyped in a small group (157 patients and 118 control subjects); next, three of the initial single-nucleotide polymorphisms were further genotyped in the overall population. In addition, WDR3 expression was investigated in 10 thyroid cancer cell lines by RT-PCR and Western blot.


RESULTS
Haplotype analysis revealed that combination of certain WDR3 variants, such as haplotype CAT, increases the risk of thyroid cancer (odds ratio = 1.85, 95% confidence interval = 0.97-3.55, p = 0.063). Further, both messenger RNA transcription and protein expression of WDR3 were altered in human thyroid cancer cells.


CONCLUSIONS
These results indicate for the first time that WDR3 is a risk factor to thyroid cancer, suggesting its implication in the etiology of thyroid cancer.
Akdi
Abdelmounaim
A
Group of Mutagenesis, Department of Genetics and Microbiology, Faculty of Bioscience, Autonomous University of Barcelona, Bellaterra, Spain.
Giménez
Esteban-Mariano
EM
García-Quispes
Wilser
W
Pastor
Susana
S
Castell
Juan
J
Biarnés
Josefina
J
Marcos
Ricard
R
Velázquez
Antonia
A
D018263:Adenocarcinoma, Follicular / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015854:Up-Regulation; D055815:Young Adult
D009687:Nuclear Proteins; D012333:RNA, Messenger; C120702:WDR3 protein, human