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

Marcello, Marjory Alana; Malandrino, Pasqualino; Almeida, Jacqueline Fátima Martins de; Martins, Mariana Bonjiorno; Cunha, Lucas Leite; Bufalo, Natassia Elena; Pellegriti, Gabriella; Ward, Laura Sterian

doi:10.1530/erc-14-0131

Cited by 50 publications

(43 citation statements)

References 173 publications

(181 reference statements)

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“…Among the several risk factors suggested to contribute to DTC, exposure to ionizing radiation (IR) remains the best-established one (1,4). Heritability is high (familial risk is one of the highest among cancers not showing typical Mendelian inheritance), suggesting that genetic factors (most likely, multiple common low-penetrance or rare moderate-penetrance alleles) strongly contribute to DTC predisposition (5).…”

Section: Introductionmentioning

confidence: 99%

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Santos

Silva

et al. 2018

Oncol Lett

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Thyroid cancer (TC) is the most common endocrine malignancy and its incidence continues to rise worldwide. Ionizing radiation exposure is the best established etiological factor. Heritability is high; however, despite valuable contribution from recent genome-wide association studies, the current understanding of genetic susceptibility to TC remains limited. Several studies suggest that altered function or expression of the DNA mismatch repair (MMR) system may contribute to TC pathogenesis. Therefore, the present study aimed to evaluate the potential role of a panel of MMR single nucleotide polymorphisms (SNPs) on the individual susceptibility to well-differentiated TC (DTC). A case-control study was performed involving 106 DTC patients and 212 age- and gender-matched controls, who were all Caucasian Portuguese. Six SNPs present in distinct MMR genes ( rs1799977, rs26279, rs5745325, rs5742933, rs175080 and rs1042821) were genotyped through TaqMan assays and genotype-associated risk estimates were calculated. An increased risk was observed in rs1042821 variant homozygotes [adjusted odds ratio (OR)=3.42, 95% CI: 1.04-11.24, P=0.04, under the co-dominant model; adjusted OR=3.84, 95% CI: 1.18-12.44, P=0.03, under the recessive model]. The association was especially evident for the follicular histotype and female sex. The association was also apparent when was analysed in combination with other MMR SNPs such as rs26279. Interestingly, two other SNP combinations, both containing the heterozygous genotype, were associated with a risk reduction, suggesting a protective effect for these genotype combinations. These data support the idea that MMR SNPs such as rs1042821, alone or in combination, may contribute to DTC susceptibility. This is coherent with the limited evidence available. Nevertheless, further studies are needed to validate these findings and to establish the usefulness of these SNPs as genetic susceptibility biomarkers for DTC so that, in the near future, cancer prevention policies may be optimized under a personalized medicine perspective.

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Section: Introductionmentioning

confidence: 99%

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Santos

Silva

et al. 2018

Oncol Lett

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“…This finding could be explained by the significant decrease in RET/PTC over the years and the equivalent increasing rate of BRAFV600E and RAS mutations in PTC, possibly attributed to the decreased exposure to ionizing radiation in the last decades or to new pollutants (75,76,77,78,79).…”

Section: Discussionmentioning

confidence: 99%

Break–apart interphase fluorescence in situ hybridization assay in papillary thyroid carcinoma: on the road to optimizing the cut-off level for RET/PTC rearrangements

Colato

Vicentini

Cantara

et al. 2015

European Journal of Endocrinology

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Objective: Chromosomal rearrangements of the RET proto-oncogene is one of the most common molecular events in papillary thyroid carcinoma (PTC). However, their pathogenic role and clinical significance are still debated. This study aimed to investigate the prevalence of RET/PTC rearrangement in a cohort of BRAF WT PTCs by fluorescence in situ hybridization (FISH) and to search a reliable cut-off level in order to distinguish clonal or non-clonal RET changes. Design: Forty BRAF WT PTCs were analyzed by FISH for RET rearrangements. As controls, six BRAFV600E mutated PTCs, 13 follicular adenomas (FA), and ten normal thyroid parenchyma were also analyzed. Methods: We performed FISH analysis on formalin-fixed, paraffin-embedded tissue using a commercially available RET break-apart probe. A cut-off level equivalent to 10.2% of aberrant cells was accepted as significant. To validate FISH results, we analyzed the study cohort by qRT-PCR. Results: Split RET signals above the cut-off level were observed in 25% (10/40) of PTCs, harboring a percentage of positive cells ranging from 12 to 50%, and in one spontaneous FA (1/13, 7.7%). Overall, the data obtained by FISH matched well with qRT-PCR results. Challenging findings were observed in five cases showing a frequency of rearrangement very close to the cut-off. Conclusions: FISH approach represents a powerful tool to estimate the ratio between broken and non-broken RET tumor cells. Establishing a precise FISH cut-off may be useful in the interpretation of the presence of RET rearrangement, primarily when this strategy is used for cytological evaluation or for targeted therapy.

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“…As a matter of fact, Neapolitan patients mainly came from the areas around the volcano Vesuvius and Campi Flegrei, which are exposed to volcanic minerals, according to ARPA data [25]. Therefore, this phenomenon of age anticipation could be related to the exposure to one or more volcanic carcinogens (in particular heavy metals) [21][22][23][32][33][34][35][36]. It has already been reported that high heavy metal concentration in the soil or water would act as endocrine disruptors, increasing the risk for thyroid cancer in younger age because their [37].…”

Section: Discussionmentioning

confidence: 99%

“…In Italy, this limit could be avoided thanks to the territorial limited extension, the more homogeneous population and the comparable lifestyle in all regions [20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

How do etiological factors can explain the different clinical features of patients with differentiated thyroid cancer and their histopathological findings?

et al. 2016

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The aim was to retrospectively analyse the clinical-histopathological characteristics of patients with newly diagnosis of differentiated thyroid cancer (DTC) referred to two Italian centres, one in Northern and the other in Southern Italy, between 2000 and 2013. 1081 patients were included and subdivided into two groups: group A (474 patients from Novara) and group B (607 patients from Naples). The group A came from the industrial area of Novara, while the Group B came from the areas around Vesuvius and Campi Flegrei. The two groups were comparable for iodine levels, body mass index, diagnostic timing and clinical procedures. For all patients, demographic and clinical data were collected. No difference was found in gender, whereas the age at diagnosis was later in the group A (group A 53.1 ± 15.16 years, group B 41.9 ± 14.25 years, p < 0.001). In both groups, the most frequent histotype was papillary thyroid cancer (PTC) with prevalence of follicular variant in group A (p < 0.0001) and classical variant in group B (p < 0.0001). Aggressive histological features were mainly seen in group A (bilaterality p < 0.0001, multifocality p < 0.0001 and thyroid capsular invasion p < 0.0001). Microcarcinomas were more frequent in group A (p < 0.0001) but mostly characterized by bilaterality (p < 0.001) and multifocality (p < 0.04). In both groups, tumour-associated thyroiditis showed a significant increase over the years (group A p < 0.05, group B p < 0.04). Environmental factors could justify the differences found in our study. These preliminary data should stimulate the need for an Italian Cancer Registry of DTC in order to allow an epidemiological characterization, allowing the identification of specific etiological factors and an improvement in the management of the disease.

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

Cited by 50 publications

References 173 publications

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Mismatch repair single nucleotide polymorphisms and thyroid cancer susceptibility

Break–apart interphase fluorescence in situ hybridization assay in papillary thyroid carcinoma: on the road to optimizing the cut-off level for RET/PTC rearrangements

How do etiological factors can explain the different clinical features of patients with differentiated thyroid cancer and their histopathological findings?

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