Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility

Hosgood, H. Dean; Cawthon, Richard M.; He, Xingzhou; Chanock, Stephen J.; Lan, Qing

doi:10.1016/j.lungcan.2009.02.005

Cited by 72 publications

(58 citation statements)

References 32 publications

(47 reference statements)

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“…Jin Eun Choi et al found that 8 SNPs of hpot1 in which 2 SNPs are the risk factors in lung cancer (Choi et al, 2009). Hosgood, H. D also found hpot1 genetic variations in lung cancer tissues (Hosgood et al, 2009). Nan, H et al have demonstrated that there are hpot1genetic point variations in skin cancer (Nan et al, 2011).…”

Section: Discussionmentioning

confidence: 91%

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Liu

Pu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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To investigate the expression of hPOT1 in the HeLa cell line and screen point mutations of hpot1 in different tumor tissues a two step osmotic method was used to extract nuclear proteins. EMSA was performed to determine the expression of hPOT1 in the HeLa cell line. PCR was also employed to amplify the exon14 sequence of the hpot1 gene in various of cancer tissues. A SV gel and PCR clean-up system was performed to enrich PCR products. DNAStar was used to analyse the exon14 sequence of the hpot1 gene. hPOT1 was expressed in the HeLa cell line and the signal was gradually enhanced as the amount of extracted nuclear proteins increased. The DNA fragment of exon14 of hpot1 was successfully amplified in the HeLa cell line and all cancer tissues, point mutations being observed in 2 out of 3 cases of endometrial cancer (66.7%) despite the hpot1 sequence being highly conserved. However, the sequence of hpot1 exon14 do not demonstrate point mutations in most cancer tissues. Since hPOT1 was expressed in HeLa cell and the probability of gene point variants was obviously higher in endometrial cancer than other cancers, it may be involved in the pathogenesis of gynecological cancers, especially in cervix and endometrium.

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Section: Discussionmentioning

confidence: 91%

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Liu

Pu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…First, hTERT has an important role at very early stages of carcinogenesis, its expression has been linked to increased susceptibility to tumorigenesis, and rs2075786 has been associated with cancer risk. 15,16,18,19,28,29 And second, through GWAS, genetic variants located in genes involved in telomere maintenance, and in particular in hTERT, were also associated with increased risk to cancer. [20][21][22][23][24][25][26][27] In contrast to previous studies examining the role of modifier genes, 11 our study includes two independent series of MMR gene mutation carriers, of 255 and 675 individuals, the latest being among the largest series used to study genetic modifiers of LS.…”

Section: Rs2075786 and Telomere Lengthmentioning

confidence: 99%

“…[20][21][22][23][24][25][26][27] Among the better characterized cancer variants, the hTERT rs2075786 (c.2654 þ 269G/A) SNP has been associated with lung cancer risk. 28,29 However, no studies have reported any association between variants located at the hTERT locus and the risk of CRC.…”

Section: Introductionmentioning

confidence: 99%

Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome

et al. 2012

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Lynch syndrome (LS) is an inherited cancer-predisposing disorder caused by germline mutations in the mismatch repair (MMR) genes. The high variability in individual cancer risk observed among LS patients suggests the existence of modifying factors. Identifying genetic modifiers of risk could help implement personalized surveillance programs based on predicted cancer risks. Here we evaluate the role of the telomerase (hTERT) rs2075786 SNP as a cancer-risk modifier in LS, studying 255 and 675 MMR gene mutation carriers from Spain and the Netherlands, respectively. The study of the Spanish sample revealed that the minor allele (A) confers increased cancer risk at an early age. The analysis of the Dutch sample confirmed the association of the A allele, especially in homozygosity, with increased cancer risk in mutation carriers under the age of 45 (relative risk LScao45_AA ¼ 2.90; 95% confidence interval ¼ 1.02-8.26). Rs2075786 is associated with colorectal cancer (CRC) risk neither in the general population nor in non-Lynch CRC families. In silico studies predicted that the SNP causes the disruption of a transcription binding site for a retinoid receptor, retinoid X receptor alpha, probably causing early telomerase activation and therefore accelerated carcinogenesis. Notably, cancer-affected LS patients with the AA genotype have shorter telomeres than those with GG. In conclusion, MMR gene mutation carriers with hTERT rs2075786 are at high risk to develop a LS-related tumor at an early age. Cancer-preventive measures and stricter cancer surveillance at early ages might help prevent or early detect cancer in these mutation carriers.

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“…In recent years, several epidemiological studies (case-control and/or cohort) have reported on the association between TL and a number of cancers such as lung, 7,8 breast, [9][10][11] bladder, 12,13 renal, 14,15 gastric, 16,17 esophageal, 18,19 colorectal, 20,21 and lymphomas. 22,23 Interestingly, according to the most recent meta-analysis on TL and cancer, reported results of What's new?…”

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confidence: 99%

Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study

et al. 2014

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Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B‐cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case–control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p = 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2–4, respectively, p‐trend = 0.001], diffuse large B‐cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2–4, respectively, p‐trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2–4, respectively, p‐trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.

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Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility

Cited by 72 publications

References 32 publications

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Expression of hPOT1 in HeLa Cells and the Probability of Gene Variation of hpot1 Exon14 in Endometrial Cancer are Much Higher than in Other Cancers

Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome

Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study

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