The Frequency of Selected Polymorphic Variants of the RET Gene in Patients with Medullary Thyroid Carcinoma and in the General Population of Central Poland

Sromek, Maria; Czetwertyńska, Małgorzata; Skasko, E.; Zielińska, Joanna; Czapczak, Dorota; Steffen, Jan

doi:10.1007/s12022-010-9125-8

Cited by 20 publications

(29 citation statements)

References 29 publications

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“…Here, we found no differences in the frequency of G691S/S904S(COG) polymorphisms between MTC patients and controls. However, similar to others, we observed that both L769L(TOG) and S836S(COT) polymorphisms were associated with increased risk for MTC (9,16,17,18,31).…”

Section: Discussionsupporting

confidence: 90%

“…Bioinformatic analysis showed differences in minimal free energy (MFE) structures in the case of exon 13. The L769L (TOG) variant reduces the energy of the wild type by 17% and the mutant Y791F by 7%, leading the authors to conclude that the L769L polymorphism reduces the MFE of small RET mRNA (17). It is also possible that this neutral variant is in LD with an as yet unknown functional variant (22,31).…”

Section: Discussionmentioning

confidence: 99%

“…Patients with MTC younger than 30 years presented a higher frequency of the RET L769L variant than those diagnosed between 31 and 45 years (16). This polymorphism was also associated with increased risk for MTC whereas patients homozygous for the minor allele of this variant were younger at the MTC diagnosis (17). Ruiz et al (2001) (18) have demonstrated that the RET S836S variant was associated with a two-to three-fold increase in the risk of MTC in the Spanish population.…”

Section: Introductionmentioning

confidence: 92%

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

Ceolin

Siqueira²,

Ferreira³

et al. 2012

European Journal of Endocrinology

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Objective: RET single nucleotide polymorphisms (SNPs) have been implicated in the pathogenesis and progression of medullary thyroid carcinoma (MTC). Here, we investigated the influence of multiple RET variants (G691S, L769L, S836S, and S904S) on the risk of MTC and tumor behavior. Design and methods: One hundred and seven MTC patients and 308 cancer-unaffected control individuals were included. SNPs were analyzed using Custom TaqMan Genotyping Assays. Haplotypes based on the combination of allelic variants were inferred using a Bayesian statistical method. Results: The minor allele frequencies in MTC patients were as follows: L769L: 28.0%, S836S: 8.9%, and G691S/S904S: 22.2%. The RET L769L and S836S SNPs were associated with increased risk of MTC (odds ratio (OR)Z1.95, 95% CI: 1.2-3.1, PZ0.005 and ORZ2.29, 95% CI: 1.2-4.5, PZ0.017 respectively). The adjusted OR for individuals harboring haplotypes with three or more polymorphic alleles was 3.79 (95% CI: 1.5-9.5; PZ0.004), indicating an additive effect of these variants on the risk for MTC. Among MTC patients, no significant associations were observed between RET variants and age of diagnosis or tumor size but serum calcitonin levels increased according to the number of risk alleles (PZ0.003). Remarkably, patients carrying haplotypes with three or four risk alleles had increased risk for lymph node and distant metastases at diagnosis (ORZ5.84, 95% CI: 1.1-31.2, PZ0.039). Further analysis using Kaplan-Meier model demonstrated that metastatic disease occurred earlier in individuals harboring multiple risk alleles. Conclusion: Our results demonstrated an additive effect of RET polymorphic alleles on the estimated risk of developing aggressive MTC.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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

Ceolin

Siqueira²,

Ferreira³

et al. 2012

European Journal of Endocrinology

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“…The picture gets even more complicated since studies with other RET variants, such as the synonymous rs1800861 (p.Leu769Leu) and 3 0 UTR rs3026782, have led to contradictory results (Wiench et al 2004, Cebrian et al 2005, Weinhaeusel et al 2008, Sromek et al 2010. In addition, some intronic polymorphisms have been associated with sMTC, such as rs2565206 (IVS1-126 GOT; Borrego et al 2003, Fernandez et al 2004 and in LD with p.Ser836Ser, and rs2472737 (IVS14-24; Baumgartner-Parzer et al 2005).…”

Section: Ret Polymorphisms In Smtcmentioning

confidence: 99%

Association studies in thyroid cancer susceptibility: are we on the right track?

Landa¹,

Robledo²

2011

Journal of Molecular Endocrinology

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It is widely accepted that thyroid cancer is strongly determined by the individual genetic background. In this regard, it is expected that sporadic thyroid cancer is the result of multiple low-to moderate-penetrance genes interacting with each other and with the environment, thus modulating individual susceptibility. In the last years, an important number of association studies on thyroid cancer have been published, trying to determine this genetic contribution. The aim of this review is to provide a comprehensive and critical evaluation of the associations reported so far in thyroid cancer susceptibility in case-control studies performed in both non-medullary (papillary and follicular) and medullary thyroid cancers, including their potential strengths and pitfalls. We summarize the genetic variants reported to date, and stress the importance of validating the results in independent series and assessing the functional role of the associated loci.

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“…In their paper they evidenced the predisposition role of SNP L769L in the developing of sporadic MTC and also in the lowering the age of onset of MTC in carriers of the homozygous SNP L769L. [56]. At least, Pasquali and his colleagues recently reported a new SNP, V109G.…”

Section: Ret Proto-oncogene Polymorphismsmentioning

confidence: 99%

Genetic Alterations in Medullary Thyroid Cancer: Diagnostic and Prognostic Markers

Taccaliti¹,

Silvetti²,

Palmonella³

et al. 2011

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Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently essential roles in cell survival, differentiation and proliferation. Somatic or germline mutations of the RET gene play an important role in this neoplasm in development of sporadic and familial forms, respectively. Genetic diagnosis has an important role in differentiating sporadic from familiar MTC. Furthermore, depending on the location of the mutation, patients can be classified into risk classes. Therefore, genetic screening of the RET gene plays a critical role not only in diagnosis but also in assessing the prognosis and course of MTC.

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The Frequency of Selected Polymorphic Variants of the RET Gene in Patients with Medullary Thyroid Carcinoma and in the General Population of Central Poland

Cited by 20 publications

References 29 publications

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

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

Association studies in thyroid cancer susceptibility: are we on the right track?

Genetic Alterations in Medullary Thyroid Cancer: Diagnostic and Prognostic Markers

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