Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Ceolin, Lucieli; Siqueira, Débora Rodrigues; Ferreira, Carla Vaz; Romitti, Mírian; Maia, Silvana Cavalcante; Leiria, Leonardo Barbosa; Crispim, Daisy; Prolla, Patrícia Ashton; Maia, Ana Luiza Silva

doi:10.1530/eje-11-1060e

Cited by 2 publications

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“…Matching for age was not possible as MTC, especially the hereditary MTC, is known to occur in childhood and recruiting minor subjects as healthy controls for genotyping study raises ethical issues. Of all the MTC case‐control studies, some have not reported whether controls were matched whereas many have failed to obtain controls matched for age or gender . Moreover, in the absence of a clearly established lifestyle or environmental factors for MTC risk, none of the MTC SNP case‐control studies have described or matched for these factors, as is the case in our study.…”

Section: Discussionmentioning

confidence: 67%

“…A few small studies which have examined certain lifestyle related risk associations with MTC have either failed to show any risk association or have paradoxically identified a protective role of tobacco smoking and alcohol . Several case‐control studies have examined the risk association of SNPs in RET and a few other genes involved in xenobiotic metabolism and cell cycle regulation with MTC in different populations . However, most of these studies and their meta‐analysis were either inconclusive or showed contradictory results.…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2019

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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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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…These postulated mechanisms are not mutually exclusive [54]. The mutant Y791F reduces the energy of the wild type by 7% and L769L (T > G) variant the by 17%, concluding that the L769L polymorphism reduces the MFE of small RET mRNA [45,55]. Because of its cosegregation of S904S with G691S, the results obtained could be interpreted as a founder effect without influence as genetic modifier [38].…”

Section: Ret Polymorphisms and Haplotypes In Differentiated Thyroid Cmentioning

confidence: 99%

Genetic Alterations of RET: Possible Implications and Clinical Correlations in Thyroid Carcinogenesis

Mudassar¹,

Khan²,

Masoodi³

et al. 2019

Knowledges on Thyroid Cancer

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Thyroid cancers are malignant tumors in the thyroid gland. DNA polymorphisms are playing a decisive role in unscrambling the genomic basis of tumor formation and development in cancer. Thyroid cancer is influenced in a polygenic and low-penetrance manner by RET gene polymorphisms and this part of the world (North India) has not recorded any study regarding RET alterations in this very cancer. We assessed RET G691S (rs1799939), L769L (rs1800861) and S904S (rs1800863) polymorphisms by restriction fragment length polymorphism (RFLP) in order to explain their potential role in the diagnosis and prognosis of Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). In RET G691S polymorphism, the total dissemination of variant alleles (GA + AA) was 62.9% in cases as related to 44.5% in controls (P < 0.05). RET L769L variant alleles (TG + GG) was 70% in cases versus 88% in controls (P < 0.05). In RET S904S, occurrence of variant alleles (CG + GG) was 56% in cases versus 44% in controls (P < 0.05). G691S and L769L polymorphism advocate a "Dominant mode of inheritance". The S904S polymorphism approves an "Additive mode of inheritance". In conclusion, there was an over-representation of RET G691S/S904S polymorphisms and underrepresentation of L769L polymorphism in PTC and FTC patients. Additionally, our data suggest that some haplotypes (A T G, G T G and A T C) of RET may act as low penetrance alleles for predisposition of thyroid cancer.

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Additive effect of RET polymorphisms on sporadic medullary thyroid carcinoma susceptibility and tumor aggressiveness

Abstract: The authors and the journal apologise for an error in the name of one of the co-authors of this article published in the May 2012 (vol 166, No 5) issue of the European Journal of Endocrinology (pp 847–854). The correct name should be Patrícia Ashton-Prolla and not as published.

Cited by 2 publications

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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

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

Genetic Alterations of RET: Possible Implications and Clinical Correlations in Thyroid Carcinogenesis

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