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 (ORZ3.87; 95% CIZ2.11-7.10; PZ2.2!10 K5) and TP53C/C genotypes (ORZ3.87; 95% CIZ1.78-6.10; PZ2.8!10 K4) 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.

Polymorphisms of cell cycle control genes influence the development of sporadic medullary thyroid carcinoma

“…The CDKN1B V109G polymorphism was reported to influence the clinical course of patients presenting sporadic MTC (15). In addition, cell cycle and apoptosis regulators have long been recognized as critical in the initiation of malignant cell proliferation and this study has recently demonstrated the influence of the presence of a C homozygous allele for the TP53 gene on the susceptibility to s-MTC (17).…”

“…Individuals with a history of past thyroid disease and antecedents of malignancy were excluded. An in-person questionnaire, described previously, was used to collect demographic and health condition information (17). All data, including nodule size, tumor histological features, and laboratory test results, were confirmed using the hospital records of the patient.…”

“…Nine polymorphisms were genotyped: CDKN1A (rs1801270 and rs1059234), CDKN1B (rs2066827 and rs34330), CDKN2A (rs11515), CDKN2B (rs2069426, rs3731239, and rs1063192), and CDKN2C (rs12885) using the TaqMan system (Applied Biosystems), as described previously (17). These SNPs were chosen because they have previously been associated with thyroid carcinoma or other tumor risks as described in Table 1 (13,15,16,20,21,22).…”

Thyroid: Medullary carcinoma

“…Studies have identified single nucleotide polymorphisms within HRAS among patient haplotypes shown to be associated with sporadic MTC. (Ruiz-Llorente et al, 2007; Barbieri, 2012). …”

The influence of the environment on the development of thyroid tumors: a new appraisal

“…In another study, our group also demonstrated that NAT2 increases susceptibility to sporadic medullary thyroid carcinoma (Barbieri et al 2012), and that CYP1A2*F, GSTP1, and NAT2 might also play an important role in the risk for hereditary medullary thyroid carcinoma (Barbieri et al 2013).…”