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8 results on '"Pasquali, C."'

1. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

Author

Obazee, O., Archibugi, L., Andriulli, A., Soucek, P., Malecka-Panas, E., Ivanauskas, A., Johnson, T., Gazouli, M., Pausch, T., Lawlor, R. T., Cavestro, G. M., Milanetto, A. C., Di Leo, M., Pasquali, C., Hegyi, P., Szentesi, A., Radu, C. E., Gheorghe, C., Theodoropoulos, G. E., Bergmann, F., Brenner, H., Vodickova, L., Katzke, V., Campa, D., Strobel, O., Kaiser, J., Pezzilli, R., Federici, F., Mohelnikova-Duchonova, B., Boggi, U., Lemstrova, R., Johansen, J. S., Bojesen, S. E., Chen, I., Jensen, B. V., Capurso, G., Pazienza, V., Dervenis, C., Sperti, C., Mambrini, A., Hackert, T., Kaaks, R., Basso, D., Talar-Wojnarowska, R., Maiello, E., Izbicki, J. R., Cuk, K., Saum, K. U., Cantore, M., Kupcinskas, J., Palmieri, O., Delle Fave, G., Landi, S., Salvia, R., Fogar, P., Vashist, Y. K., Scarpa, A., Vodicka, P., Tjaden, C., Iskierka-Jazdzewska, E., Canzian, F., Obazee, O., Archibugi, L., Andriulli, A., Soucek, P., Malecka-Panas, E., Ivanauskas, A., Johnson, T., Gazouli, M., Pausch, T., Lawlor, R. T., Cavestro, G. M., Milanetto, A. C., Di Leo, M., Pasquali, C., Hegyi, P., Szentesi, A., Radu, C. E., Gheorghe, C., Theodoropoulos, G. E., Bergmann, F., Brenner, H., Vodickova, L., Katzke, V., Campa, D., Strobel, O., Kaiser, J., Pezzilli, R., Federici, F., Mohelnikova-Duchonova, B., Boggi, U., Lemstrova, R., Johansen, J. S., Bojesen, S. E., Chen, I., Jensen, B. V., Capurso, G., Pazienza, V., Dervenis, C., Sperti, C., Mambrini, A., Hackert, T., Kaaks, R., Basso, D., Talar-Wojnarowska, R., Maiello, E., Izbicki, J. R., Cuk, K., Saum, K. U., Cantore, M., Kupcinskas, J., Palmieri, O., Delle Fave, G., Landi, S., Salvia, R., Fogar, P., Vashist, Y. K., Scarpa, A., Vodicka, P., Tjaden, C., Iskierka-Jazdzewska, E., and Canzian, F.

Subjects
Male, Cancer Research, pancreatic cancer, Genes, BRCA2, I157T, Polymorphism, Single Nucleotide, Humans, Genetic Predisposition to Disease, Germ-Line Mutation, Aged, BRCA2 Protein, K3326X, PANDoRA consortium, rs11571833, rs17879961, Oncology, Pancreatic cancer, Middle Aged, Pancreatic Neoplasms, Checkpoint Kinase 2, Case-Control Studies, Female, Carcinoma, Pancreatic Ductal
Abstract

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Published
2018

2. Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma

Author

Obazee, O., primary, Archibugi, L., additional, Andriulli, A., additional, Soucek, P., additional, Małecka-Panas, E., additional, Ivanauskas, A., additional, Johnson, T., additional, Gazouli, M., additional, Pausch, T., additional, Lawlor, R. T., additional, Cavestro, G. M., additional, Milanetto, A. C., additional, Di Leo, M., additional, Pasquali, C., additional, Hegyi, P., additional, Szentesi, A., additional, Radu, C. E., additional, Gheorghe, C., additional, Theodoropoulos, G. E., additional, Bergmann, F., additional, Brenner, H., additional, Vodickova, L., additional, Katzke, V., additional, Campa, D., additional, Strobel, O., additional, Kaiser, J., additional, Pezzilli, R., additional, Federici, F., additional, Mohelnikova-Duchonova, B., additional, Boggi, U., additional, Lemstrova, R., additional, Johansen, J. S., additional, Bojesen, S. E., additional, Chen, I., additional, Jensen, B. V., additional, Capurso, G., additional, Pazienza, V., additional, Dervenis, C., additional, Sperti, C., additional, Mambrini, A., additional, Hackert, T., additional, Kaaks, R., additional, Basso, D., additional, Talar-Wojnarowska, R., additional, Maiello, E., additional, Izbicki, J. R., additional, Cuk, K., additional, Saum, K. U., additional, Cantore, M., additional, Kupcinskas, J., additional, Palmieri, O., additional, Delle Fave, G., additional, Landi, S., additional, Salvia, R., additional, Fogar, P., additional, Vashist, Y. K., additional, Scarpa, A., additional, Vodicka, P., additional, Tjaden, C., additional, Iskierka-Jazdzewska, E., additional, and Canzian, F., additional

Published
2019
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3. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation

Author

Campa, D, Pastore, M, Capurso, G, Hackert, T, Di Leo, M, Izbicki, JR, Khaw, K-T, Gioffreda, D, Kupcinskas, J, Pasquali, C, Macinga, P, Kaaks, R, Stigliano, S, Peeters, PH, Key, TJ, Talar-Wojnarowska, R, Vodicka, P, Valente, R, Vashist, YK, Salvia, R, Papaconstantinou, I, Shimizu, Y, Valsuani, C, Zambon, CF, Gazouli, M, Valantiene, I, Niesen, W, Mohelnikova-Duchonova, B, Hara, K, Soucek, P, Malecka-Panas, E, Bueno-de-Mesquita, HBA, Johnson, T, Brenner, H, Tavano, F, Fogar, P, Ito, H, Sperti, C, Butterbach, K, Latiano, A, Andriulli, A, Cavestro, GM, Busch, ORC, Dijk, F, Greenhalf, W, Matsuo, K, Lombardo, C, Strobel, O, König, A-K, Cuk, K, Strothmann, H, Katzke, V, Cantore, M, Mambrini, A, Oliverius, M, Pezzilli, R, Landi, S, Canzian, F, Other departments, CCA - Imaging and biomarkers, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Campa, Daniele, Pastore, Manuela, Capurso, Gabriele, Hackert, Thilo, Di Leo, Milena, Izbicki, Jakob R, Khaw, Kay tee, Gioffreda, Domenica, Kupcinskas, Juoza, Pasquali, Claudio, Macinga, Peter, Kaaks, Rudolf, Stigliano, Serena, Peeters, Petra H, Key, Timothy J, Talar wojnarowska, Renata, Vodicka, Pavel, Valente, Roberto, Vashist, Yogesh K, Salvia, Roberto, Papaconstantinou, Ioanni, Shimizu, Yasuhiro, Valsuani, Chiara, Zambon, Carlo Federico, Gazouli, Maria, Valantiene, Irena, Niesen, Willem, Mohelnikova duchonova, Beatrice, Hara, Kazuo, Soucek, Pavel, Malecka panas, Ewa, Bueno de mesquita, H. Ba, Johnson, Theron, Brenner, Herman, Tavano, Francesca, Fogar, Paola, Ito, Hidemi, Sperti, Cosimo, Butterbach, Katja, Latiano, Anna, Andriulli, Angelo, Cavestro, GIULIA MARTINA, Busch, Olivier R. C, Dijk, Frederike, Greenhalf, William, Matsuo, Keitaro, Lombardo, Carlo, Strobel, Oliver, König, Anna katharina, Cuk, Katarina, Strothmann, Hendrik, Katzke, Verena, Cantore, Maurizio, Mambrini, Andrea, Oliverius, Martin, Pezzilli, Raffaele, Landi, Stefano, and Canzian, Federico

Subjects
Adult, Male, Cancer Research, endocrine system diseases, Chronic pancreatiti, pancreatic ductal adenocarcinoma, Adenocarcinoma, Polymorphism, Single Nucleotide, genetic polymorphisms, Risk Factors, Pancreatitis, Chronic, Biomarkers, Tumor, genetic polymorphism, Humans, Trypsin, Chronic, Polymorphism, Aged, Retrospective Studies, Tumor, Carcinoma, association, Nuclear Proteins, Single Nucleotide, Middle Aged, ACUTE PANCREATITIS, Prognosis, digestive system diseases, PANCREATIC CANCER, Pancreatic Neoplasms, Pancreatitis, Oncology, Pancreatic Ductal, Case-Control Studies, Chronic pancreatitis, Carcinoma, Pancreatic Ductal, Female, Follow-Up Studies, Trypsinogen, Biomarkers
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639 rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous =1.19, 95% CI 1.02-1.38, p=0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous =0.51, 95% CI 0.39-0.67, p=1.10x10(-6) ) and MORC4-rs 12837024 (ORhomozygous =2.07 (1.55-2.77, ptrend =0.7x10(-11) ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639 rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants. This article is protected by copyright. All rights reserved.

Published
2017

4. Potential association between PSCA rs2976395 functional variant and pancreatic cancer risk.

Author

Corradi C, Lencioni G, Felici A, Rizzato C, Gentiluomo M, Ermini S, Archibugi L, Mickevicius A, Lucchesi M, Malecka-Wojciesko E, Basso D, Arcidiacono PG, Petrone MC, Carrara S, Götz M, Bunduc S, Holleczek B, Aoki MN, Uzunoglu FG, Zanette DL, Mambrini A, Jamroziak K, Oliverius M, Lovecek M, Cavestro GM, Milanetto AC, Peduzzi G, Duchonova BM, Izbicki JR, Zalinkevicius R, Hlavac V, van Eijck CHJ, Brenner H, Vanella G, Vokacova K, Soucek P, Tavano F, Perri F, Capurso G, Hussein T, Kiudelis M, Kupcinskas J, Busch OR, Morelli L, Theodoropoulos GE, Testoni SGG, Adamonis K, Neoptolemos JP, Gazouli M, Pasquali C, Kormos Z, Skalicky P, Pezzilli R, Sperti C, Kauffmann E, Büchler MW, Schöttker B, Hegyi P, Capretti G, Lawlor RT, Canzian F, and Campa D

Subjects
Humans, Male, Case-Control Studies, White People genetics, Female, Quantitative Trait Loci, Alleles, Asian People genetics, Middle Aged, Polymorphism, Single Nucleotide, Pancreatic Neoplasms genetics, Genetic Predisposition to Disease, DNA Methylation, Carcinoma, Pancreatic Ductal genetics, GPI-Linked Proteins genetics, Linkage Disequilibrium, Antigens, Neoplasm genetics, Neoplasm Proteins genetics
Abstract

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10 -5 ). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association., (© 2024 UICC.)

Published
2024
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5. Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Author

Corradi C, Gentiluomo M, Gajdán L, Cavestro GM, Kreivenaite E, Di Franco G, Sperti C, Giaccherini M, Petrone MC, Tavano F, Gioffreda D, Morelli L, Soucek P, Andriulli A, Izbicki JR, Napoli N, Małecka-Panas E, Hegyi P, Neoptolemos JP, Landi S, Vashist Y, Pasquali C, Lu Y, Cervena K, Theodoropoulos GE, Moz S, Capurso G, Strobel O, Carrara S, Hackert T, Hlavac V, Archibugi L, Oliverius M, Vanella G, Vodicka P, Arcidiacono PG, Pezzilli R, Milanetto AC, Lawlor RT, Ivanauskas A, Szentesi A, Kupcinskas J, Testoni SGG, Lovecek M, Nentwich M, Gazouli M, Luchini C, Zuppardo RA, Darvasi E, Brenner H, Gheorghe C, Jamroziak K, Canzian F, and Campa D

Subjects
Aged, Case-Control Studies, Computational Biology methods, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Carcinoma, Pancreatic Ductal genetics, Cyclin-Dependent Kinase Inhibitor p15 genetics, MicroRNAs genetics, Pancreatic Neoplasms genetics, Polymorphism, Single Nucleotide, RNA, Long Noncoding genetics
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10 -9 ). This SNP is located in the NONHSAG053086.2 (lnc-SMC2-1) gene and the risk allele is predicted to disrupt the binding of the lncRNA with the micro-RNA (miRNA) hsa-mir-1256 that regulates several genes involved in cell cycle, such as CDKN2B. The CDKN2B region is pleiotropic and its genetic variants have been associated with several human diseases, possibly though an imperfect interaction between lncRNA and miRNA. We present a novel PDAC risk locus, supported by a genome-wide statistical significance and a plausible biological mechanism., (© 2021 UICC.)

Published
2021
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6. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study.

Author

Campa D, Matarazzi M, Greenhalf W, Bijlsma M, Saum KU, 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 KT, König AK, 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, and Canzian F

Subjects
Aged, Case-Control Studies, Europe, Female, Genome-Wide Association Study, Humans, Lymphocytes metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Telomerase metabolism, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms genetics, Ribonucleoproteins genetics, Telomerase genetics, Telomere metabolism, Telomere Shortening genetics
Abstract

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 , p trend = 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., (© 2018 UICC.)

Published
2019
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7. Do pancreatic cancer and chronic pancreatitis share the same genetic risk factors? A PANcreatic Disease ReseArch (PANDoRA) consortium investigation.

Author

Campa D, Pastore M, Capurso G, Hackert T, Di Leo M, Izbicki JR, Khaw KT, Gioffreda D, Kupcinskas J, Pasquali C, Macinga P, Kaaks R, Stigliano S, Peeters PH, Key TJ, Talar-Wojnarowska R, Vodicka P, Valente R, Vashist YK, Salvia R, Papaconstantinou I, Shimizu Y, Valsuani C, Zambon CF, Gazouli M, Valantiene I, Niesen W, Mohelnikova-Duchonova B, Hara K, Soucek P, Malecka-Panas E, Bueno-de-Mesquita HBA, Johnson T, Brenner H, Tavano F, Fogar P, Ito H, Sperti C, Butterbach K, Latiano A, Andriulli A, Cavestro GM, Busch ORC, Dijk F, Greenhalf W, Matsuo K, Lombardo C, Strobel O, König AK, Cuk K, Strothmann H, Katzke V, Cantore M, Mambrini A, Oliverius M, Pezzilli R, Landi S, and Canzian F

Subjects
Adenocarcinoma genetics, Adenocarcinoma pathology, Adult, Aged, Carcinoma, Pancreatic Ductal pathology, Case-Control Studies, Female, Follow-Up Studies, Humans, Male, Middle Aged, Nuclear Proteins genetics, Pancreatic Neoplasms pathology, Pancreatitis, Chronic pathology, Prognosis, Retrospective Studies, Risk Factors, Trypsin genetics, Trypsinogen genetics, Biomarkers, Tumor genetics, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms genetics, Pancreatitis, Chronic genetics, Polymorphism, Single Nucleotide
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (OR homozygous  = 1.19, 95% CI 1.02-1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (OR heterozygous  = 0.51, 95% CI 0.39-0.67, p = 1.10 × 10 -6 ) and MORC4-rs 12837024 (OR homozygous  = 2.07 (1.55-2.77, p trend  = 0.7 × 10 -11 ). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants., (© 2017 UICC.)

Published
2018
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8. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility.

Author

Campa D, Rizzato C, Stolzenberg-Solomon R, Pacetti P, Vodicka P, Cleary SP, Capurso G, Bueno-de-Mesquita HB, Werner J, Gazouli M, Butterbach K, Ivanauskas A, Giese N, Petersen GM, Fogar P, Wang Z, Bassi C, Ryska M, Theodoropoulos GE, Kooperberg C, Li D, Greenhalf W, Pasquali C, Hackert T, Fuchs CS, Mohelnikova-Duchonova B, Sperti C, Funel N, Dieffenbach AK, Wareham NJ, Buring J, Holcátová I, Costello E, Zambon CF, Kupcinskas J, Risch HA, Kraft P, Bracci PM, Pezzilli R, Olson SH, Sesso HD, Hartge P, Strobel O, Małecka-Panas E, Visvanathan K, Arslan AA, Pedrazzoli S, Souček P, Gioffreda D, Key TJ, Talar-Wojnarowska R, Scarpa A, Mambrini A, Jacobs EJ, Jamroziak K, Klein A, Tavano F, Bambi F, Landi S, Austin MA, Vodickova L, Brenner H, Chanock SJ, Delle Fave G, Piepoli A, Cantore M, Zheng W, Wolpin BM, Amundadottir LT, and Canzian F

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Linkage Disequilibrium, Male, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Young Adult, Carcinoma, Pancreatic Ductal genetics, Pancreatic Neoplasms genetics, Telomerase genetics
Abstract

A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 × 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D' = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 × 10(-5) ), rs4583925 (p = 4.0 × 10(-5) ) and rs2735948 (p = 5.0 × 10(-5) ). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants., (© 2015 UICC.)

Published
2015
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