<i>TERT</i> Genetic Polymorphism rs2736100 Was Associated with Lung Cancer: A Meta-Analysis Based on 14,492 Subjects

Wang, Huimin; Zhang, Xueyan; Jin, Bo

doi:10.1089/gtmb.2013.0322

Cited by 14 publications

(8 citation statements)

References 22 publications

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“…We found that TERT rs2736100 was still significantly associated with lung cancer when incorporated with many environmental and lifestyle factors. Overall, our data were consist with those from meta-analyses 38 - 40 , thus providing evidence that this locus is strongly associated with the development of the disease.…”

Section: Discussionsupporting

confidence: 75%

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility

Wang¹,

Ma²,

Chi³

et al. 2016

J. Cancer

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Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.

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Section: Discussionsupporting

confidence: 75%

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility

Wang¹,

Ma²,

Chi³

et al. 2016

J. Cancer

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“…It has been thoroughly associated with lung cancer risk (mostly adenocarcinoma [ 242 , 249 ]), although there were also reports of no evident association [ 386 ]. Wang et al [ 387 ] and Yang et al [ 388 ] published meta-analyses in which they reported the association of rs2736100 with increased lung cancer risk (mainly adenocarcinoma) in both Caucasian and Asian populations. This SNP was identified to associate with an increased risk of myeloproliferative neoplasms (e.g., polycythaemia vera, essential thrombocythemia, and primary myelofibrosis) in Caucasian and Chinese populations [ 267 , 269 ].…”

Section: Telomere Maintenance Mechanismsmentioning

confidence: 99%

Telomere Maintenance Mechanisms in Cancer

Gaspar

Sá

Lopes

et al. 2018

Genes

107

135

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Tumour cells can adopt telomere maintenance mechanisms (TMMs) to avoid telomere shortening, an inevitable process due to successive cell divisions. In most tumour cells, telomere length (TL) is maintained by reactivation of telomerase, while a small part acquires immortality through the telomerase-independent alternative lengthening of telomeres (ALT) mechanism. In the last years, a great amount of data was generated, and different TMMs were reported and explained in detail, benefiting from genome-scale studies of major importance. In this review, we address seven different TMMs in tumour cells: mutations of the TERT promoter (TERTp), amplification of the genes TERT and TERC, polymorphic variants of the TERT gene and of its promoter, rearrangements of the TERT gene, epigenetic changes, ALT, and non-defined TMM (NDTMM). We gathered information from over fifty thousand patients reported in 288 papers in the last years. This wide data collection enabled us to portray, by organ/system and histotypes, the prevalence of TERTp mutations, TERT and TERC amplifications, and ALT in human tumours. Based on this information, we discuss the putative future clinical impact of the aforementioned mechanisms on the malignant transformation process in different setups, and provide insights for screening, prognosis, and patient management stratification.

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“…In particular, TERT polymorphisms are especially associated with ADC in never-smokers. Moreover, GWAS strongly suggest that both TERT and CLPTM1L polymorphisms actually modify the susceptibility to further develop a lung cancer (20)(21)(22)(23)(24).…”

Section: Genome-wide Association Studies (Gwas)mentioning

confidence: 99%

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

et al. 2017

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Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC. Thus, current classification differentiates between preinvasive lesions (atypical adenomatous hyperplasia and in situ ADC), minimally invasive ADC (MIA) and invasive ADC. 'Field cancerization' is a concept that refers to progressive loco-regional changes occurring in tissues exposed to carcinogens, due to the interaction of the latter with a predisposing genetic background and an appropriate tissue microenvironment. Somatic genetic alterations, including mutations but also other changes, are necessary for oncogenesis, being especially frequent in lung ADC. Changes in the epidermal growth factor receptor () gene, Kirsten rat sarcoma viral oncogene (), v-Raf murine sarcoma viral oncogene homolog B (), gene encoding neurofibromin (), anaplastic lymphoma kinase () and are the main genes that suffer alterations in the tumors of patients with ADC. Molecular profiling of these tumors allows more targeted treatments through two distinct strategies, genome-guided therapy and immunotherapy. The former, targets the aberrant pathways secondary to the genomic alteration, whereas the latter may be based on the administration of antibodies [such as those against cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the programmed cell death ligand 1/protein 1 pathway (PD-L1/PD-1)] or the stimulation of the patient's own immune system to produce a specific response. These strategies are obtaining better results in selected ADC patients.

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TERT Genetic Polymorphism rs2736100 Was Associated with Lung Cancer: A Meta-Analysis Based on 14,492 Subjects

Cited by 14 publications

References 22 publications

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility

Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility

Telomere Maintenance Mechanisms in Cancer

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

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