Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer.
OBJECTIVE
Xenobiotic-metabolizing enzymes are widely polymorphic and confer interindividual variation in the ability to detoxify carcinogens or to activate pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in lack of enzyme activity and has been associated with an altered susceptibility to several cancers. The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer (PTC).


METHODS
Retrospective case-control study.


METHODS
One hundred and eighty-seven patients with PTC and 256 controls.


METHODS
Genotyping was performed by PCR and restriction enzyme analysis to detect the presence of the common CYP2D6*4 poor metaboliser allele.


RESULTS
The frequency of individuals with the homozygous poor metaboliser genotype was lower in the patient group [1.6 vs. 5.5%, P = 0.037, OR = 0.28 (95% CI 0.09-0.93)]. The CYP2D6*4 allele frequency was also lower in the patient group [13.4 vs. 21.7%, P = 0.002, OR = 0.56 (95% CI 0.39-0.80)].


CONCLUSIONS
The results suggest that the poor metaboliser genotype is associated with a protective effect against PTC. This could be explained by a possible role of CYP2D6 on the metabolic activation of putative environmental chemical thyroid carcinogens or by linkage to another cancer-causing gene. Further research may allow the identification of metabolic risk factors and contribute towards understanding the molecular mechanisms involved in thyroid carcinogenesis.
Lemos
Manuel C
MC
Centro de Investigação em Ciências da Saúde (CICS), Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal. mclemos@fcsaude.ubi.pt
Carrilho
Francisco
F
Rodrigues
Fernando
F
Coutinho
Eduarda
E
Gomes
Leonor
L
Carvalheiro
Manuela
M
Regateiro
Fernando J
FJ
D000231:Adenocarcinoma, Papillary / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000235:genetics*
D019389:Cytochrome P-450 CYP2D6