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Genetic polymorphism of CYP2D6 influences susceptibility to papillary thyroid cancer
Author(s) -
Lemos Manuel C.,
Carrilho Francisco,
Rodrigues Fernando,
Coutinho Eduarda,
Gomes Leonor,
Carvalheiro Manuela,
Regateiro Fernando J.
Publication year - 2007
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2007.02858.x
Subject(s) - cyp2d6 , genotype , genotyping , biology , medicine , pharmacogenetics , carcinogenesis , allele , carcinogen , allele frequency , endocrinology , thyroid cancer , genetics , cancer , oncology , gene
Summary 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). Design Retrospective case‐control study. Patients One hundred and eighty‐seven patients with PTC and 256 controls. Measurements 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.