Lung cancer susceptibility locus at 5p15.33

McKay, James; Hung, Rayjean J.; Gaborieau, Valérie; Boffetta, Paolo; Chabrier, Amélie; Byrnes, Graham; Заридзе, Давид; Mukeria, Anush; Szeszenia-Dabrowska, Neonilia; Lissowska, Jolanta; Rudnai, Péter; Fabiánovà, Eleonóra; Mateș, Dana; Bencko, Vladimír; Foretová, Lenka; Janout, Vladimí­r; McLaughlin, John; Shepherd, Frances A.; Montpetit, Alexandre; Narod, Steven A.; Krokan, Hans E.; Skorpen, Frank; Elvestad, Maiken B.; Vatten, Lars J.; Njølstad, Inger; Axelsson, Tomas; Chu, Chen; Goodman, Gary E.; Barnett, Matt J.; Loomis, Melissa M.; Lubiński, Jan; Matyjasik, Joanna; Lener, Marcin; Oszutowska, Dorota; Field, John K.; Liloglou, Triantafillos; Xinarianos, George; Cassidy, Adrian; Zélénika, Diana; Boland, Anne; Délépine, Marc; Foglio, Mario; Lechner, Doris; Matsuda, Fumihiko; Blanché, Hélène; Gut, Ivo; Heath, Simon; Lathrop, Mark; Brennan, Paul

doi:10.1038/ng.254

Cited by 509 publications

(435 citation statements)

References 15 publications

Supporting

Mentioning

417

Contrasting

Order By: Relevance

“…[17][18][19] Genetic variants located in genes involved in telomere maintenance, and in particular in hTERT (MIM 187270), the gene encoding the catalytic subunit of telomerase, have been associated with increased risk to cancer. [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

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

View full text Add to dashboard Cite

show abstract

“…2,[5][6][7][8][9][10][11] The genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) gene regions could play a role in MM etiology for two reasons: first the two genes are responsible for crucial cellular processes, namely telomere homeostasis, second their polymorphic variants have been found to be associated with multiple cancer types and other human phenotypes. [12][13][14][15][16][17][18][19][20][21][22][23][24] TERT and TERC constitute the telomerase complex, 25 whose correct functioning is fundamental for the accurate de novo synthesis of telomeric ends. Even moderate changes in TERT and TERC activity could profoundly affect telomere homeostasis.…”

mentioning

confidence: 99%

“…30 It is not, therefore, surprising that it harbors multiple variants associated with risk of different diseases and in particular with various cancer types. For example the rs2736100 SNP is associated with glioma, testicular and lung cancer, 16,18,20 while rs401681 is associated with lung, bladder and pancreatic cancer, 17,19,21 rs10069690 with estrogen receptor-negative breast cancer 12,13 and rs2242652 with breast, prostate and ovarian cancer. 12,14,15 In addition, TERT polymorphisms are associated with other human phenotypes such as pulmonary fibrosis and PSA levels.…”

mentioning

confidence: 99%

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Campa

Martino

Várkonyi

et al. 2014

Intl Journal of Cancer

View full text Add to dashboard Cite

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; ptrend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.

show abstract

“…[88][89][90] The combination of three GWAS further identified additional susceptibility loci for this common cancer, 75 where one of the loci (5p15.33) was also identified by another GWAS. 91 The 5p15.33 locus contains two genes, TERT and CLPTM1L, and interestingly the sequence variants at this locus were found to be associated with several cancers. 92 Although these studies firmly identified the 15q25 locus for lung cancer, the underlying associations were different between the studies.…”

Section: The Recent 2 Years: 2008 and 2009mentioning

confidence: 99%

The pursuit of genome-wide association studies: where are we now?

et al. 2010

View full text Add to dashboard Cite

It is now 5 years since the first genome-wide association studies (GWAS), published in 2005, identified a common risk allele with large effect size for age-related macular degeneration in a small sample set. Following this exciting finding, researchers have become optimistic about the prospect of the genome-wide association approach. However, most of the risk alleles identified in the subsequent GWAS for various complex diseases are common with small effect sizes (odds ratio o1.5). So far, more than 450 GWAS have been published and the associations of greater than 2000 single nucleotide polymorphisms (SNPs) or genetic loci were reported. The aim of this review paper is to give an overview of the evolving field of GWAS, discuss the progress that has been made by GWAS and some of the interesting findings, and summarize what we have learned over the past 5 years about the genetic basis of human complex diseases. This review will focus on GWAS of SNPs association for complex diseases but not studies of copy number variations.

show abstract

Lung cancer susceptibility locus at 5p15.33

Cited by 509 publications

References 15 publications

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

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

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

The pursuit of genome-wide association studies: where are we now?

Contact Info

Product

Resources

About