Association of newly identified genetic variant rs2853677 of TERT with non-small cell lung cancer and leukemia in population of Jammu and Kashmir, India

Abstract

Background Telomere genetics has recently been emerged as an important field in molecular oncology. Various genome-wide association studies in different population groups have revealed that polymorphisms in Telomere maintenance gene ( TERT ) gene located on 5p15.33 is associated with susceptibility to leukemia and lung cancer risk. However, association of TERT with leukemia and lung cancer risk in north Indian population groups is still unknown. This study observed the association between genetic variant rs2853677 of TERT and leukemia and lung cancer in the state of Jammu and Kashmir, India. Methods A total of 781 subjects, out of which 381 cases (203 leukemic patients and 178 non-small cell lung cancer patients NSCLC) and 400 healthy controls were recruited for the study. Genetic variant rs2853677of TERT was detected using the real-time and Taqman Chemistry. Hardy-Weinberg Equilibrium was assessed using the chi square test. The allele and genotype- specific risks were estimated as odds ratio with 95% confidence interval. Results We observed that variant rs2853677 was strongly associated with lung cancer and leukemia risk with an odds ratio (OR) =1.8 (1.03–3.2 at 95% CI); p value (adjusted) = 0.03; odds ratio (OR) =2.9 (1.4–5.5.at 95% CI); p value (adjusted) = 0.002, respectively. Conclusion The results of this study suggested that rs2853677 of TERT signifies association in multiple cancers and suggests that it can become potential marker for diagnosis of non-small cell lung cancer and leukemia. The study will provide an insight in understanding the genetic etiology and highlights the role of telomere-associated pathways in non-small cell lung cancer and leukemia. However, it would be quite interesting to explore the contribution of this variant in other cancers as well. Electronic supplementary material The online version of this article (10.1186/s12885-019-5685-2) contains supplementary material, which is available to authorized users.

Recessive effects in cancer predisposition exposed by genome-wide and proteome-wide association studies

“…Mutations in TERT can cause abnormal activities of the telomerase and prevent telomere shortening, thereby leading to cell immortality. rs2853677 has been implicated in various Chinese and Indian populations [52,53]. We provide evidence for the clinical importance of this variant in the white British population.…”

REV3L Gene Variants rs1002481, rs462779, and rs465646 Lead to Increased Susceptibility Towards Non-Small Cell Lung Cancer in the Population of Jammu and Kashmir.

“…Genotyping of the selected SNVs was performed using the allele discrimination assay on the MX3005p Agilent Real-time PCR platform and we adopted the methodology from our previous studies [4,6] conditions were adopted; hold for 10 min at 95 °C, then 40 cycles of 95 °C for 15 s and 60 °C for 1 min. All the samples were run in 96-well plates with three no template control (NTC).…”

“…One recent study has put lung cancer as the second most common cancer in the J&K region with 23.5% of all new cases in 2017 [3]. Although several studies have evaluated mutations in key genes, such as genes involved in cell cycle and cell growth regulation, in DNA damage repair pathways and many other pathways with reference to different cancer types in the population of J&K [4][5][6][7], none has evaluated the role of Translesion Synthesis (TLS) polymerase in any cancer type. The DNA sequence can get altered as the result of replication error and by the environmental agents such as tobacco smoking, mutagenic chemicals, and certain types of radiation, which may lead to cancer [8][9][10].…”

REV3L gene variants rs1002481, rs462779, and rs465646 lead to increased susceptibility towards non-small cell lung cancer in the population of Jammu and Kashmir.

“…Genotyping of the selected SNVs was performed using the allele discrimination assay on the MX3005p Agilent Real-time PCR platform and then, methodology was adopted from previous studies [5,7] DNA (5 ng/μl) and 4.25 μl nuclease-free water to make up the nal volume. The following thermal conditions were adopted; held for 10 min at 95 °C, then 40 cycles of 95 °C for 15 s and 60 °C for 1 min.…”

“…One recent study claimed lung cancer as the second most common cancer in the J&K region with 23.5 % of all new cases in 2017 [4]. Although several studies have evaluated mutations in key genes, such as genes involved in cell cycle and cell growth regulation, in DNA damage repair pathways and many other pathways with reference to different cancer types in the population of J&K [5][6][7][8], none has evaluated the role of Translesion Synthesis (TLS) polymerase in any cancer type. The DNA sequence can get altered as the result of replication error and/or by the environmental agents such as tobacco smoking, mutagenic chemicals, and certain types of radiation, which may lead to cancer [9][10][11].…”