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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 ,  m ay be of importance to disease process and may be associated with papillary thyroid cancer risk in Saudi Arabian population.

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