Evidence that polymorphisms in detoxification genes modulate the susceptibility for sporadic medullary thyroid carcinoma

Abstract

Aim: Polymorphic low-penetrance genes have been consistently associated with the susceptibility to a series of human tumors, including differentiated thyroid cancer. Methods: To determine their role in medullary thyroid cancer (MTC), we used TaqMan SNP method to genotype 47 sporadic MTC (s-MTC) and a control group of 578 healthy individuals for CYP1A2*F, CYP1A1m1, GSTP1, NAT2 and 72TP53. A logistic regression analysis showed that NAT2C/C (OR=3.87; 95% CI=2.11-7.10; P=2.2×10 -5) and TP5 3C/C genotypes (OR=3.87; 95% CI=1.78-6.10; P=2.8×10 -4) inheritance increased the risk of s-MTC. A stepwise regression analysis indicated that TP53C/C genotype contributes with 8.07% of the s-MTC risk. Results: We were unable to identify any relationship between NAT2 and TP53 polymorphisms suggesting they are independent factors of risk to s-MTC. In addition, there was no association between the investigated genes and clinical or pathological features of aggressiveness of the tumors or the outcome of MTC patients. Conclusion: In conclusion,we demonstrated that detoxification genes and apoptotic and cell cycle control genes are involved in the susceptibility of s-MTC and may modulate the susceptibility to the disease. © 2012 European Society of Endocrinology.