Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study
Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization appro...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2018
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| _version_ | 1797077788709093376 |
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| author | Campa, D Matarazzi, M Greenhalf, W Bijlsma, M Saum, K-U Pasquali, C Van Laarhoven, H Szentesi, A Federici, F Vodicka, P Funel, N Pezzilli, R Bueno-De-Mesquita, HB Vodickova, L Basso, D Obazee, O Hackert, T Soucek, P Cuk, K Kaiser, J Sperti, C Lovecek, M Capurso, G Mohelnikova-Duchonova, B Khaw, K-T König, A-K Kupcinskas, J Kaaks, R Bambi, F Archibugi, L Mambrini, A Cavestro, GM Landi, S Hegyi, P Izbicki, JR Gioffreda, D Zambon, CF Tavano, F Talar-Wojnarowska, R Jamroziak, K Key, TJ Fave, GD Strobel, O Jonaitis, L Andriulli, A Lawlor, RT Pirozzi, F Katzke, V Valsuani, C Vashist, YK Brenner, H Canzian, F |
| author_facet | Campa, D Matarazzi, M Greenhalf, W Bijlsma, M Saum, K-U Pasquali, C Van Laarhoven, H Szentesi, A Federici, F Vodicka, P Funel, N Pezzilli, R Bueno-De-Mesquita, HB Vodickova, L Basso, D Obazee, O Hackert, T Soucek, P Cuk, K Kaiser, J Sperti, C Lovecek, M Capurso, G Mohelnikova-Duchonova, B Khaw, K-T König, A-K Kupcinskas, J Kaaks, R Bambi, F Archibugi, L Mambrini, A Cavestro, GM Landi, S Hegyi, P Izbicki, JR Gioffreda, D Zambon, CF Tavano, F Talar-Wojnarowska, R Jamroziak, K Key, TJ Fave, GD Strobel, O Jonaitis, L Andriulli, A Lawlor, RT Pirozzi, F Katzke, V Valsuani, C Vashist, YK Brenner, H Canzian, F |
| author_sort | Campa, D |
| collection | OXFORD |
| description | Telomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. |
| first_indexed | 2024-03-07T00:23:02Z |
| format | Journal article |
| id | oxford-uuid:7d32547a-885e-4cdf-91e9-93f9e29dc688 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:23:02Z |
| publishDate | 2018 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:7d32547a-885e-4cdf-91e9-93f9e29dc6882022-03-26T21:02:06ZGenetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7d32547a-885e-4cdf-91e9-93f9e29dc688EnglishSymplectic Elements at OxfordWiley2018Campa, DMatarazzi, MGreenhalf, WBijlsma, MSaum, K-UPasquali, CVan Laarhoven, HSzentesi, AFederici, FVodicka, PFunel, NPezzilli, RBueno-De-Mesquita, HBVodickova, LBasso, DObazee, OHackert, TSoucek, PCuk, KKaiser, JSperti, CLovecek, MCapurso, GMohelnikova-Duchonova, BKhaw, K-TKönig, A-KKupcinskas, JKaaks, RBambi, FArchibugi, LMambrini, ACavestro, GMLandi, SHegyi, PIzbicki, JRGioffreda, DZambon, CFTavano, FTalar-Wojnarowska, RJamroziak, KKey, TJFave, GDStrobel, OJonaitis, LAndriulli, ALawlor, RTPirozzi, FKatzke, VValsuani, CVashist, YKBrenner, HCanzian, FTelomere deregulation is a hallmark of cancer. Telomere length measured in lymphocytes (LTL) has been shown to be a risk marker for several cancers. For pancreatic ductal adenocarcinoma (PDAC) consensus is lacking whether risk is associated with long or short telomeres. Mendelian randomization approaches have shown that a score built from SNPs associated with LTL could be used as a robust risk marker. We explored this approach in a large scale study within the PANcreatic Disease ReseArch (PANDoRA) consortium. We analyzed 10 SNPs (ZNF676-rs409627, TERT-rs2736100, CTC1-rs3027234, DHX35-rs6028466, PXK-rs6772228, NAF1-rs7675998, ZNF208-rs8105767, OBFC1-rs9420907, ACYP2-rs11125529 and TERC-rs10936599) alone and combined in a LTL genetic score ("teloscore", which explains 2.2% of the telomere variability) in relation to PDAC risk in 2,374 cases and 4,326 controls. We identified several associations with PDAC risk, among which the strongest were with the TERT-rs2736100 SNP (OR = 1.54; 95%CI 1.35-1.76; p = 1.54 × 10-10 ) and a novel one with the NAF1-rs7675998 SNP (OR = 0.80; 95%CI 0.73-0.88; p = 1.87 × 10-6 , ptrend = 3.27 × 10-7 ). The association of short LTL, measured by the teloscore, with PDAC risk reached genome-wide significance (p = 2.98 × 10-9 for highest vs. lowest quintile; p = 1.82 × 10-10 as a continuous variable). In conclusion, we present a novel genome-wide candidate SNP for PDAC risk (TERT-rs2736100), a completely new signal (NAF1-rs7675998) approaching genome-wide significance and we report a strong association between the teloscore and risk of pancreatic cancer, suggesting that telomeres are a potential risk factor for pancreatic cancer. |
| spellingShingle | Campa, D Matarazzi, M Greenhalf, W Bijlsma, M Saum, K-U Pasquali, C Van Laarhoven, H Szentesi, A Federici, F Vodicka, P Funel, N Pezzilli, R Bueno-De-Mesquita, HB Vodickova, L Basso, D Obazee, O Hackert, T Soucek, P Cuk, K Kaiser, J Sperti, C Lovecek, M Capurso, G Mohelnikova-Duchonova, B Khaw, K-T König, A-K Kupcinskas, J Kaaks, R Bambi, F Archibugi, L Mambrini, A Cavestro, GM Landi, S Hegyi, P Izbicki, JR Gioffreda, D Zambon, CF Tavano, F Talar-Wojnarowska, R Jamroziak, K Key, TJ Fave, GD Strobel, O Jonaitis, L Andriulli, A Lawlor, RT Pirozzi, F Katzke, V Valsuani, C Vashist, YK Brenner, H Canzian, F Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title_full | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title_fullStr | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title_full_unstemmed | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title_short | Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study |
| title_sort | genetic determinants of telomere length and risk of pancreatic cancer a pandora study |
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