TY - JOUR ID - 89089 TI - Modulatory Role of Single Nucleotide Polymorphisms of Distinct Genetic Pathways on Clinical Behavior of Medullary Thyroid Carcinoma JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Mishra, Vasudha AU - Kowtal, Pradnya AU - Rane, Pallavi AU - Sarin, Rajiv AD - Sarin Lab, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India. AD - 3Clinical Research Centre (CRC), Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, India. Y1 - 2020 PY - 2020 VL - 21 IS - 5 SP - 1289 EP - 1293 KW - Medullary thyroid carcinoma KW - MTC KW - RET KW - SNP KW - Association-study DO - 10.31557/APJCP.2020.21.5.1289 N2 - Background: Role of RET proto-oncogene as predisposing gene for Medullary Thyroid Carcinoma is well established which provides the basis for clinical management of patients. However clinical behavior of MTC varies considerably among patients. Several studies have investigated whether SNPs in low penetrance genes could modulate the clinical behavior of MTC but with conflicting or inconclusive results. The present study aimed to investigate the modifier effect of 13 SNPs of three distinct genetic pathways -Detoxification, Cell cycle regulation and RET on the clinico-pathological features of hereditary and sporadic MTC. Methods: SNPs were genotyped using RFLP or TaqMan method. The genotypes were correlated with various clinico-pathological parameters (age and calcitonin levels at MTC diagnosis, tumor volume, nodal and distant metastasis). Results: Nodal metastasis was the only clinico-pathological parameter showing significant association with any SNP. In the hereditary MTC group (n=77), incidence of nodal metastases was significantly higher in wild type allele for Cyp1A1m1, CDKN2A and CDKN2C (p=0.01 for all three). In sporadic MTC group (n=361) CDKN2C wild type allele had higher nodal metastasis (p=0.03). Conclusion: In this largest MTC cohort with comprehensive analysis of modulatory role of 13 most frequently studied SNPs with MTC clinical outcome, we observed a statistically significant association of few SNPs with nodal metastasis. However as these SNPs did not show association with any other clinico-pathological parameters like tumor volume or Calcitonin, they may not be true modifier of MTC. Additional large cohort studies with clinico-pathological details and long-term follow-up are needed to identify genetic modifiers of MTC behavior. UR - https://journal.waocp.org/article_89089.html L1 - https://journal.waocp.org/article_89089_850c9f8ac10c2d12a6d433a7ac9655b8.pdf ER -