Research article

Polymorphisms of selected Xenobiotic Genes contribute to the development of Papillary Thyroid Cancer susceptibility in Middle Eastern population

Abdul K Siraj¹ , Muna Ibrahim¹ , Maha Al-Rasheed¹ , Jehad Abubaker¹ , Rong Bu¹ , Shakaib U Siddiqui¹ , Fouad Al-Dayel² , Osama Al-Sanea³ , Abdulrahman Al-Nuaim⁴ , Shahab Uddin¹ and Khawla Al-Kuraya¹

¹Cancer Genomics, Research Centre, King Fahad National Center for Children's Cancer & Research, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

²Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

³Health Sciences Centre, Saad Specialist Hospital, Al-Khobar, Saudi Arabia

⁴Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

author email corresponding author email

BMC Medical Genetics 2008, 9:61doi:10.1186/1471-2350-9-61

Published:	5 July 2008

Abstract

Background

The xenobiotic enzyme system that enables us to detoxify carcinogens exhibits identifiable genetic polymorphisms that are highly race specific. We hypothesized that polymorphisms of these genes may be associated with risk of thyroid cancer. To evaluate the role of genetic polymorphisms of xenobiotic genes in thyroid cancer, we conducted a hospital-based case-control study in Saudi population.

Methods

223 incident papillary thyroid cancer cases and 513 controls recruited from Saudi Arabian population were analyzed for the association between polymorphisms in genes encoding folic acid metabolizing enzymes MTHFR and six xenobiotics-metabolizing enzymes including CYP1A1 T3801C, C4887A, GSTP1 A1578G, C2293T, GSTM1, GSTT1, NAT2 G590A, NQO*1 C609T, using PCR-RELP.

Results

Among selected genes, CYP1A1 C4887A genotypes CA, AA and variant allele A demonstrated significant differences and greater risk of developing thyroid cancer comparing to wild type genotype CC (CA vs. CC; p < 0.0001, OR = 1.91, 95% CI = 1.36–2.70, AA vs. CC; p < 0.001, OR = 3.48, 95% CI = 1.74–6.96 and CA+AA vs. CC; p < 0.0001, OR = 2.07, 95% CI = 1.49–2.88). GSTT1 null showed 3.48 times higher risk of developing thyroid cancer (p < 0.0001, 95% CI = 2.48–4.88) while GSTM1 null showed protective effect (p < 0.05, OR = 0.72, 95% CI = 0.52–0.99). Remaining loci demonstrated no significance with risk.

Conclusion

Of the 9 polymorphisms screened, we identified GST, GSTM1 and CYP1A1 C4887A, may be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population.