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Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis

BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk associatio...

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Autores principales: Mishra, Vasudha, Kowtal, Pradnya, Rane, Pallavi, Sarin, Rajiv
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792509/
https://www.ncbi.nlm.nih.gov/pubmed/31408923
http://dx.doi.org/10.1002/cam4.2443
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author Mishra, Vasudha
Kowtal, Pradnya
Rane, Pallavi
Sarin, Rajiv
author_facet Mishra, Vasudha
Kowtal, Pradnya
Rane, Pallavi
Sarin, Rajiv
author_sort Mishra, Vasudha
collection PubMed
description BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. METHODS: In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. RESULTS: Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P < .001) and sporadic MTC (OR 0.53; 95% CI 0.36‐0.78; P = .001). An increased risk association was identified for NAT2Y94Y SNP (OR 1.62, 95% CI 1.17‐2.25, P = .004) and CDKN2A3′UTR SNP (OR 1.89, 95% CI 1.19‐2.98, P = .006) with sporadic MTC and RET S904S with hereditary MTC (OR 2.82, 95% CI 1.64‐4.86, P < .001). Meta‐analysis of RET SNPs including our cohort identified increased risk association of all four RET SNPs with MTC. CONCLUSION: In this largest SNP risk association study for MTC and the only risk association study of the 13 most commonly studied MTC associated SNPs in a single cohort of this rare cancer, a significant protective risk association of CDKN1ASer31Arg SNP with MTC was shown for the first time. Meta‐analysis identified significant risk association of all four RET SNPs, not observed in previous meta‐analysis.
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spelling pubmed-67925092019-10-21 Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis Mishra, Vasudha Kowtal, Pradnya Rane, Pallavi Sarin, Rajiv Cancer Med Cancer Prevention BACKGROUND: Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. METHODS: In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. RESULTS: Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P < .001) and sporadic MTC (OR 0.53; 95% CI 0.36‐0.78; P = .001). An increased risk association was identified for NAT2Y94Y SNP (OR 1.62, 95% CI 1.17‐2.25, P = .004) and CDKN2A3′UTR SNP (OR 1.89, 95% CI 1.19‐2.98, P = .006) with sporadic MTC and RET S904S with hereditary MTC (OR 2.82, 95% CI 1.64‐4.86, P < .001). Meta‐analysis of RET SNPs including our cohort identified increased risk association of all four RET SNPs with MTC. CONCLUSION: In this largest SNP risk association study for MTC and the only risk association study of the 13 most commonly studied MTC associated SNPs in a single cohort of this rare cancer, a significant protective risk association of CDKN1ASer31Arg SNP with MTC was shown for the first time. Meta‐analysis identified significant risk association of all four RET SNPs, not observed in previous meta‐analysis. John Wiley and Sons Inc. 2019-08-13 /pmc/articles/PMC6792509/ /pubmed/31408923 http://dx.doi.org/10.1002/cam4.2443 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Prevention
Mishra, Vasudha
Kowtal, Pradnya
Rane, Pallavi
Sarin, Rajiv
Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title_full Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title_fullStr Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title_full_unstemmed Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title_short Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis
title_sort genetic risk association of cdkn1a and ret gene snps with medullary thyroid carcinoma: results from the largest mtc cohort and meta‐analysis
topic Cancer Prevention
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792509/
https://www.ncbi.nlm.nih.gov/pubmed/31408923
http://dx.doi.org/10.1002/cam4.2443
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