Search

Your search keyword '"Pasquali, C."' showing total 282 results
Start Over Author "Pasquali, C." Search Limiters Available in Library Collection
282 results on '"Pasquali, C."'

2. Duodenal Gastric Metaplasia and Duodenal Neuroendocrine Neoplasms: More Than a Simple Coincidence?

Author

Massironi, S, Rossi, R, Milanetto, A, Andreasi, V, Campana, D, Nappo, G, Partelli, S, Gallo, C, Scaravaglio, M, Zerbi, A, Panzuto, F, Pasquali, C, Falconi, M, Invernizzi, P, Massironi S., Rossi R. E., Milanetto A. C., Andreasi V., Campana D., Nappo G., Partelli S., Gallo C., Scaravaglio M., Zerbi A., Panzuto F., Pasquali C., Falconi M., Invernizzi P., Massironi, S, Rossi, R, Milanetto, A, Andreasi, V, Campana, D, Nappo, G, Partelli, S, Gallo, C, Scaravaglio, M, Zerbi, A, Panzuto, F, Pasquali, C, Falconi, M, Invernizzi, P, Massironi S., Rossi R. E., Milanetto A. C., Andreasi V., Campana D., Nappo G., Partelli S., Gallo C., Scaravaglio M., Zerbi A., Panzuto F., Pasquali C., Falconi M., and Invernizzi P.

Abstract

Background: Duodenal gastric metaplasia (DGM) is considered a precancerous lesion. No data are available regarding its possible role as a risk factor for duodenal neuroendocrine neoplasms (dNENs). Aims: To assess the prevalence of DGM in a cohort of dNENs. Methods: Subgroup analysis of a retrospective study including dNEN patients who underwent surgical resection between 2000 and 2019 and were observed at eight Italian tertiary referral centers. Results: 109 dNEN patients were evaluated. Signs of DGM associated with the presence of dNEN were reported in 14 patients (12.8%). Among these patients, nine (64.4%) had a dNEN of the superior part of the duodenum, one (7.1%) a periampullary lesion, three (21.4%) a dNEN located in the second portion of the duodenum, with a different localization distribution compared to patients without DGM (p = 0.0332). Ten were G1, three G2, and in one patient the Ki67 was not available. In the group with DGM, six patients (35.7%) were classified at stage I, five (28.6%) at stage II, three (21.4%) at stage III, and no one at stage IV. In the group without DGM, 20 patients (31%) were at stage I, 15 (15%) at stage II, 42 (44%) at stage III, and 19 (20%) at stage IV (p = 0.0236). At the end of the study, three patients died because of disease progression. Conclusions: our findings might suggest that DGM could represent a feature associated with the occurrence of dNEN, especially for forms of the superior part of the duodenum, which should be kept in mind in the endoscopic follow up of patients with DGM. Interestingly, dNEN inside DGM showed a more favorable staging, with no patients in stage IV. The actual relationship and the clinical relevance of this possible association require further clarification.

Published
2022

8. Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy

Author

Rossi, R, Milanetto, A, Andreasi, V, Campana, D, Coppa, J, Nappo, G, Rinzivillo, M, Invernizzi, P, Modica, R, David, A, Partelli, S, Lamberti, G, Mazzaferro, V, Zerbi, A, Panzuto, F, Pasquali, C, Falconi, M, Massironi, S, Rossi R. E., Milanetto A. C., Andreasi V., Campana D., Coppa J., Nappo G., Rinzivillo M., Invernizzi P., Modica R., David A., Partelli S., Lamberti G., Mazzaferro V., Zerbi A., Panzuto F., Pasquali C., Falconi M., Massironi S., Rossi, R, Milanetto, A, Andreasi, V, Campana, D, Coppa, J, Nappo, G, Rinzivillo, M, Invernizzi, P, Modica, R, David, A, Partelli, S, Lamberti, G, Mazzaferro, V, Zerbi, A, Panzuto, F, Pasquali, C, Falconi, M, Massironi, S, Rossi R. E., Milanetto A. C., Andreasi V., Campana D., Coppa J., Nappo G., Rinzivillo M., Invernizzi P., Modica R., David A., Partelli S., Lamberti G., Mazzaferro V., Zerbi A., Panzuto F., Pasquali C., Falconi M., and Massironi S.

Abstract

Purpose: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. Methods: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. Results: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. Conclusions: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

Published
2021

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

Author

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

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

10. Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk

Author

Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., Canzian, F., Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., and Canzian, F.

Abstract

Genetic factors play an important role in the susceptibility to pancreatic cancer (PC). However, established loci explain a small proportion of genetic heritability for PC; therefore, more progress is needed to find the missing ones. We aimed at identifying single nucleotide polymorphisms (SNPs) affecting PC risk through effects on micro-RNA (miRNA) function. We searched in silico the genome for SNPs in miRNA seed sequences or 3 prime untranslated regions (3'UTRs) of miRNA target genes. Genome-wide association data of PC cases and controls from the Pancreatic Cancer Cohort (PanScan) Consortium and the Pancreatic Cancer Case–Control (PanC4) Consortium were re-analyzed for discovery, and genotyping data from two additional consortia (PanGenEU and PANDoRA) were used for replication, for a total of 14,062 cases and 11,261 controls. None of the SNPs reached genome-wide significance in the meta-analysis, but for three of them the associations were in the same direction in all the study populations and showed lower value of p in the meta-analyses than in the discovery phase. Specifically, rs7985480 was consistently associated with PC risk (OR = 1.12, 95% CI 1.07–1.17, p = 3.03 × 10−6 in the meta-analysis). This SNP is in linkage disequilibrium (LD) with rs2274048, which modulates binding of various miRNAs to the 3'UTR of UCHL3, a gene involved in PC progression. In conclusion, our results expand the knowledge of the genetic PC risk through miRNA-related SNPs and show the usefulness of functional prioritization to identify genetic polymorphisms associated with PC risk.

Published
2021

11. Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk

Author

Sub ISEP overig, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., Canzian, F., Sub ISEP overig, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., and Canzian, F.

Published
2021

12. Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk

Author

Sub IER overig, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., Canzian, F., Sub IER overig, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Lu, Y., Corradi, C., Gentiluomo, M., López de Maturana, E., Theodoropoulos, G.E., Roth, S., Maiello, E., Morelli, L., Archibugi, L., Izbicki, J.R., Sarlós, P., Kiudelis, V., Oliverius, M., Aoki, M.N., Vashist, Y., van Eijck, C.H.J., Gazouli, M., Talar-Wojnarowska, R., Mambrini, A., Pezzilli, R., Bueno-de-Mesquita, B., Hegyi, P., Souček, P., Neoptolemos, J.P., Di Franco, G., Sperti, C., Kauffmann, E.F., Hlaváč, V., Uzunoğlu, F.G., Ermini, S., Małecka-Panas, E., Lucchesi, M., Vanella, G., Dijk, F., Mohelníková-Duchoňová, B., Bambi, F., Petrone, M.C., Jamroziak, K., Guo, F., Kolarova, K., Capretti, G., Milanetto, A.C., Ginocchi, L., Loveček, M., Puzzono, M., van Laarhoven, H.W.M., Carrara, S., Ivanauskas, A., Papiris, K., Basso, D., Arcidiacono, P.G., Izbéki, F., Chammas, R., Vodicka, P., Hackert, T., Pasquali, C., Piredda, M.L., Costello-Goldring, E., Cavestro, G.M., Szentesi, A., Tavano, F., Włodarczyk, B., Brenner, H., Kreivenaite, E., Gao, X., Bunduc, S., Vermeulen, R.C.H., Schneider, M.A., Latiano, A., Gioffreda, D., Testoni, S.G.G., Kupcinskas, J., Lawlor, R.T., Capurso, G., Malats, N., Campa, D., and Canzian, F.

Published
2021

13. Genetic determinants of telomere length and risk of pancreatic cancer: A PANDoRA study

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, 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, H. B., 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., Konig, A. -K., Kupcinskas, J., Kaaks, R., Bambi, F., Archibugi, L., Mambrini, A., Cavestro, G. M., Landi, S., Hegyi, P., Izbicki, J. R., Gioffreda, D., Zambon, C. F., Tavano, F., Talar-Wojnarowska, R., Jamroziak, K., Key, T. J., Fave, G. D., Strobel, O., Jonaitis, L., Andriulli, A., Lawlor, R. T., Pirozzi, F., Katzke, V., Valsuani, C., Vashist, Y. K., Brenner, H., Canzian, F., Center of Experimental and Molecular Medicine, CCA - Cancer biology and immunology, Radiotherapy, Oncology, and AGEM - Re-generation and cancer of the digestive system

Subjects
Male, Cancer Research, pancreatic ductal adenocarcinoma, Polymorphism, Single Nucleotide, lymphocyte telomere length, genetic polymorphisms, association, Mendelian randomization, Oncology, Humans, genetic polymorphism, Lymphocytes, Telomerase, Telomere Shortening, Aged, Pancreatic Neoplasm, Ribonucleoprotein, Middle Aged, Telomere, Pancreatic Neoplasms, Europe, Ribonucleoproteins, Case-Control Studies, Female, Lymphocyte, Case-Control Studie, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study, Human
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.

Published
2019

21. 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

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

Author

Obazee, O. Archibugi, L. Andriulli, A. Soucek, P. Małecka-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.

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
2019

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

Author

Obazee, O, Archibugi, L, Andriulli, A, Soucek, P, Małecka-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, Małecka-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

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 <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Published
2019

30. Corrigendum: Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms [Carcinogenesis, 39, 3, (2018), (360-367)] DOI: 10.1093/carcin/bgx150

Author

Obazee, O. Capurso, G. Tavano, F. Archibugi, L. De Bonis, A. Greenhalf, W. Key, T. Pasquali, C. Milanetto, A.C. Hackert, T. Fogar, P. Lico, V. Dervenis, C. Lawlor, R.T. Landoni, L. Gazouli, M. Zambon, C.F. Funel, N. Strobel, O. Jamroziak, K. Cantu, C. Malecka-Panas, E. Landi, S. Neoptolemos, J.P. Basso, D. Talar-Wojnarowska, R. Rinzivillo, M. Andriulli, A. Canzian, F. Campa, D.

Subjects
GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), GeneralLiterature_MISCELLANEOUS
Abstract

In the originally published version of this article, the institutional affiliations of some authors were listed incorrectly. The correct affiliations are as listed above. This has been corrected online. The authors wish to apologize for this error. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.

Published
2018

31. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, A.P. Wolpin, B.M. Risch, H.A. Stolzenberg-Solomon, R.Z. Mocci, E. Zhang, M. Canzian, F. Childs, E.J. Hoskins, J.W. Jermusyk, A. Zhong, J. Chen, F. Albanes, D. Andreotti, G. Arslan, A.A. Babic, A. Bamlet, W.R. Beane-Freeman, L. Berndt, S.I. Blackford, A. Borges, M. Borgida, A. Bracci, P.M. Brais, L. Brennan, P. Brenner, H. Bueno-De-Mesquita, B. Buring, J. Campa, D. Capurso, G. Cavestro, G.M. Chaffee, K.G. Chung, C.C. Cleary, S. Cotterchio, M. Dijk, F. Duell, E.J. Foretova, L. Fuchs, C. Funel, N. Gallinger, S. Gaziano, J.M.M. Gazouli, M. Giles, G.G. Giovannucci, E. Goggins, M. Goodman, G.E. Goodman, P.J. Hackert, T. Haiman, C. Hartge, P. Hasan, M. Hegyi, P. Helzlsouer, K.J. Herman, J. Holcatova, I. Holly, E.A. Hoover, R. Hung, R.J. Jacobs, E.J. Jamroziak, K. Janout, V. Kaaks, R. Khaw, K.-T. Klein, E.A. Kogevinas, M. Kooperberg, C. Kulke, M.H. Kupcinskas, J. Kurtz, R.J. Laheru, D. Landi, S. Lawlor, R.T. Lee, I.-M. Lemarchand, L. Lu, L. Malats, N. Mambrini, A. Mannisto, S. Milne, R.L. Mohelníková-Duchoňová, B. Neale, R.E. Neoptolemos, J.P. Oberg, A.L. Olson, S.H. Orlow, I. Pasquali, C. Patel, A.V. Peters, U. Pezzilli, R. Porta, M. Real, F.X. Rothman, N. Scelo, G. Sesso, H.D. Severi, G. Shu, X.-O. Silverman, D. Smith, J.P. Soucek, P. Sund, M. Talar-Wojnarowska, R. Tavano, F. Thornquist, M.D. Tobias, G.S. Van Den Eeden, S.K. Vashist, Y. Visvanathan, K. Vodicka, P. Wactawski-Wende, J. Wang, Z. Wentzensen, N. White, E. Yu, H. Yu, K. Zeleniuch-Jacquotte, A. Zheng, W. Kraft, P. Li, D. Chanock, S. Obazee, O. Petersen, G.M. Amundadottir, L.T.

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: Rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene. © 2018 The Author(s).

Published
2018

32. Common genetic variants associated with pancreatic adenocarcinoma may also modify risk of pancreatic neuroendocrine neoplasms

Author

Obazee, O. Capurso, G. Tavano, F. Archibugi, L. Bonis, A.D. Greenhalf, W. Key, T. Pasquali, C. Milanetto, A.C. Hackert, T. Fogar, P. Liço, V. Dervenis, C. Lawlor, R.T. Landoni, L. Gazouli, M. Zambon, C.F. Funel, N. Strobel, O. Jamroziak, K. Cantù, C. Malecka-Panas, E. Landi, S. Neoptolemos, J.P. Basso, D. Talar-Wojnarowska, R. Rinzivillo, M. Andriulli, A. Canzian, F. Campa, D.

Abstract

Pancreatic neuroendocrine neoplasms (pNEN) account for less than 5% of all pancreatic neoplasms and genetic association studies on susceptibility to the disease are limited. We sought to identify possible overlap of genetic susceptibility loci between pancreatic ductal adenocarcinoma (PDAC) and pNEN; therefore, PDAC susceptibility variants (n = 23) from Caucasian genome-wide association studies (GWAS) were genotyped in 369 pNEN cases and 3277 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium to evaluate the odds associated with pNEN risk, disease onset and tumor characteristics. Main effect analyses showed four PDAC susceptibility variants-rs9854771, rs1561927, rs9543325 and rs10919791 to be associated with pNEN risk. Subsequently, only associations with rs9543325, rs10919791 and rs1561927 were noteworthy with false positive report probability (FPRP) tests. Stratified analyses considering age at onset (50-year threshold), showed rs2736098, rs16986825 and rs9854771 to be associated with risk of developing pNEN at a younger age. Stratified analyses also showed some single nucleotide polymorphisms to be associated with different degrees of tumor grade, metastatic potential and functionality. Our results identify known GWAS PDAC susceptibility loci, which may also be involved in sporadic pNEN etiology and suggest that some genetic mechanisms governing pathogenesis of these two entities may be similar, with few of these loci being more influential in younger cases or tumor subtypes. © The Author(s) 2018. Published by Oxford University Press. All rights reserved.

Published
2018

33. 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, J.R. Khaw, K.-T. Gioffreda, D. Kupcinskas, J. Pasquali, C. Macinga, P. Kaaks, R. Stigliano, S. Peeters, P.H. Key, T.J. Talar-Wojnarowska, R. Vodicka, P. Valente, R. Vashist, Y.K. Salvia, R. Papaconstantinou, I. Shimizu, Y. Valsuani, C. Zambon, C.F. Gazouli, M. Valantiene, I. Niesen, W. Mohelnikova-Duchonova, B. Hara, K. Soucek, P. Malecka-Panas, E. Bueno-de-Mesquita, H.B. Johnson, T. Brenner, H. Tavano, F. Fogar, P. Ito, H. Sperti, C. Butterbach, K. Latiano, A. Andriulli, A. Cavestro, G.M. Busch, O.R.C. 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.

Subjects
endocrine system diseases, digestive system diseases
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 (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 = 1.10 × 10−6) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55–2.77, ptrend = 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

35. Client self-image, therapist acting, and the establishment of the therapeutic alliance in a training context

Author

Pasquali, C. E., Ybrandt, Helene, Armelius, Kerstin, Pasquali, C. E., Ybrandt, Helene, and Armelius, Kerstin

Abstract

This study examined how clients' self-image and perception of therapist's behavior are related to the therapeutic alliance, as well as how these variables change in the psychotherapy process in trainee-led psychotherapy. A total of 164 participants (M = 28.9 years) who attended two semesters of treatment at the Psychology Clinic of Umea University completed the Working Alliance Inventory (WAI) to evaluate their perception of their alliance with the therapist. They also completed two questionnaires based on the Structural Analysis of Social Behavior (SASB) model to give insight into their self-image patterns and to analyze their perceptions of the therapist's behavior. The results show that a positive self-image and positive perceptions of the therapist's actions increased significantly over the course of the therapy, with a corresponding decrease in negative patterns. The alliance scores show that the therapeutic alliance gains significance over time and that it is influenced more by the perception of the therapist's behavior than by the self-image. The self-image becomes relevant after the mid part of therapy, underlining the role of the therapist in co-creating the treatment relationship. The implications of these results are discussed, and so are directions for future research in other traineeled settings and samples.

Published
2018
Full Text
View/download PDF

36. Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

Author

Mincham, K.T., Scott, N.M., Lauzon-Joset, J-F, Leffler, J., Larcombe, A.N., Stumbles, P.A., Robertson, S.A., Pasquali, C., Holt, P.G., Strickland, D.H., Mincham, K.T., Scott, N.M., Lauzon-Joset, J-F, Leffler, J., Larcombe, A.N., Stumbles, P.A., Robertson, S.A., Pasquali, C., Holt, P.G., and Strickland, D.H.

Abstract

Chronic allergic inflammatory diseases are a major cause of morbidity, with allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either the promotion or prevention of disease. Major reductions in asthma prevalence are documented in European and US farming communities. Protection is associated with exposure of mothers during pregnancy to microbial breakdown products present in farm dusts and unprocessed foods and enhancement of innate immune competence in the children. We sought to develop a scientific rationale for progressing these findings toward clinical application for primary disease prevention. Treatment of pregnant mice with a defined, clinically approved immune modulator was shown to markedly reduce susceptibility of their offspring to development of the hallmark clinical features of allergic airway inflammatory disease. Mechanistically, offspring displayed enhanced dendritic cell–dependent airway mucosal immune surveillance function, which resulted in more efficient generation of mucosal-homing regulatory T cells in response to local inflammatory challenge. We provide evidence that the principal target for maternal treatment effects was the fetal dendritic cell progenitor compartment, equipping the offspring for accelerated functional maturation of the airway mucosal dendritic cell network following birth. These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention.

Published
2018

37. Maternal immunomodulation as a strategy to protect offspring against asthma

Author

Mincham, K.T., Scott, N.M., Lauzon-Joset, J., Leffler, J., Larcombe, A.N., Stumbles, P.A., Pasquali, C., Holt, P.G., Strickland, D.H., Mincham, K.T., Scott, N.M., Lauzon-Joset, J., Leffler, J., Larcombe, A.N., Stumbles, P.A., Pasquali, C., Holt, P.G., and Strickland, D.H.

Abstract

Studies of traditional European and US farming populations have documented major reductions in asthma prevalence in children of mothers exposed during pregnancy to microbial breakdown products present in farm dust and unprocessed foods. The mechanisms driving protection appear associated with enhancement of innate immune competence in the offspring leading to optimisation of immunoregulatory and effector cell function. The potential to therapeutically harness this environmental phenomenon represents a plausible strategy in the primary prevention of asthma. Using preclinical mouse models, we sought to identify if a safe ǀ microbial-derived immunomodulatory therapeutic could recapitulate the "farm effect" phenomenon. We demonstrate that maternal oral treatment during pregnancy with the clinically-approved bacterial-derived immunomodulator OM-85, markedly reduces the susceptibility of offspring to development of allergic airways inflammation initiated at weaning. This was exemplified by attenuation of granulocytic infiltration and airways hyperresponsiveness following airways challenge. Protection was linked to the recruitment of T-regulatory cells to airways mucosa exhibiting enhanced CTLA-4 and Foxp3 expression, with parallel attenuation of local cDC trafficking to airway draining lymph nodes and inflammation associated recruitment and activation. Moreover, these offspring display a striking attenuation of the inflammatory response in the bone marrow myeloid precursor compartments, consistent with the reduced mobilisation of cDC bone marrow reserves and granulocytic accumulation within the airways. The mechanistic actions of OM-85 on bone marrow precursors could be traced back to in utero development, whereby maternal OM-85 treatment boosts myeloid progenitor cells within fetal bone marrow whilst simultaneously accelerating DC functional immune competence as evident by upregulated IA/IE expression. In vitro validation of OM-85-induced immunomodulatory effects on bone

Published
2018

39. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author

Klein, AP, Wolpin, BM, Risch, HA, Stolzenberg-Solomon, RZ, Mocci, E, Zhang, M, Canzian, F, Childs, EJ, Hoskins, JW, Jermusyk, A, Zhong, J, Chen, F, Albanes, D, Andreotti, G, Arslan, AA, Babic, A, Bamlet, WR, Beane-Freeman, L, Berndt, SI, Blackford, A, Borges, M, Borgida, A, Bracci, PM, Brais, L, Brennan, P, Brenner, H, Bueno-de-Mesquita, B, Buring, J, Campa, D, Capurso, G, Cavestro, GM, Chaffee, KG, Chung, CC, Cleary, S, Cotterchio, M, Dijk, F, Duell, EJ, Foretova, L, Fuchs, C, Funel, N, Gallinger, S, Gaziano, JMM, Gazouli, M, Giles, GG, Giovannucci, E, Goggins, M, Goodman, GE, Goodman, PJ, Hackert, T, Haiman, C, Hartge, P, Hasan, M, Hegyi, P, Helzlsouer, KJ, Herman, J, Holcatova, I, Holly, EA, Hoover, R, Hung, RJ, Jacobs, EJ, Jamroziak, K, Janout, V, Kaaks, R, Khaw, K-T, Klein, EA, Kogevinas, M, Kooperberg, C, Kulke, MH, Kupcinskas, J, Kurtz, RJ, Laheru, D, Landi, S, Lawlor, RT, Lee, I-M, LeMarchand, L, Lu, L, Malats, N, Mambrini, A, Mannisto, S, Milne, RL, Mohelnikova-Duchonova, B, Neale, RE, Neoptolemos, JP, Oberg, AL, Olson, SH, Orlow, I, Pasquali, C, Patel, AV, Peters, U, Pezzilli, R, Porta, M, Real, FX, Rothman, N, Scelo, G, Sesso, HD, Severi, G, Shu, X-O, Silverman, D, Smith, JP, Soucek, P, Sund, M, Talar-Wojnarowska, R, Tavano, F, Thornquist, MD, Tobias, GS, Van Den Eeden, SK, Vashist, Y, Visvanathan, K, Vodicka, P, Wactawski-Wende, J, Wang, Z, Wentzensen, N, White, E, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Zheng, W, Kraft, P, Li, D, Chanock, S, Obazee, O, Petersen, GM, Amundadottir, LT, Klein, AP, Wolpin, BM, Risch, HA, Stolzenberg-Solomon, RZ, Mocci, E, Zhang, M, Canzian, F, Childs, EJ, Hoskins, JW, Jermusyk, A, Zhong, J, Chen, F, Albanes, D, Andreotti, G, Arslan, AA, Babic, A, Bamlet, WR, Beane-Freeman, L, Berndt, SI, Blackford, A, Borges, M, Borgida, A, Bracci, PM, Brais, L, Brennan, P, Brenner, H, Bueno-de-Mesquita, B, Buring, J, Campa, D, Capurso, G, Cavestro, GM, Chaffee, KG, Chung, CC, Cleary, S, Cotterchio, M, Dijk, F, Duell, EJ, Foretova, L, Fuchs, C, Funel, N, Gallinger, S, Gaziano, JMM, Gazouli, M, Giles, GG, Giovannucci, E, Goggins, M, Goodman, GE, Goodman, PJ, Hackert, T, Haiman, C, Hartge, P, Hasan, M, Hegyi, P, Helzlsouer, KJ, Herman, J, Holcatova, I, Holly, EA, Hoover, R, Hung, RJ, Jacobs, EJ, Jamroziak, K, Janout, V, Kaaks, R, Khaw, K-T, Klein, EA, Kogevinas, M, Kooperberg, C, Kulke, MH, Kupcinskas, J, Kurtz, RJ, Laheru, D, Landi, S, Lawlor, RT, Lee, I-M, LeMarchand, L, Lu, L, Malats, N, Mambrini, A, Mannisto, S, Milne, RL, Mohelnikova-Duchonova, B, Neale, RE, Neoptolemos, JP, Oberg, AL, Olson, SH, Orlow, I, Pasquali, C, Patel, AV, Peters, U, Pezzilli, R, Porta, M, Real, FX, Rothman, N, Scelo, G, Sesso, HD, Severi, G, Shu, X-O, Silverman, D, Smith, JP, Soucek, P, Sund, M, Talar-Wojnarowska, R, Tavano, F, Thornquist, MD, Tobias, GS, Van Den Eeden, SK, Vashist, Y, Visvanathan, K, Vodicka, P, Wactawski-Wende, J, Wang, Z, Wentzensen, N, White, E, Yu, H, Yu, K, Zeleniuch-Jacquotte, A, Zheng, W, Kraft, P, Li, D, Chanock, S, Obazee, O, Petersen, GM, and Amundadottir, LT

Abstract

In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

Published
2018

40. Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

Author

Mincham, K., Scott, N., Lauzon-Joset, J., Leffler, J., Larcombe, Alexander, Stumbles, P., Robertson, S., Pasquali, C., Holt, P., Strickland, D., Mincham, K., Scott, N., Lauzon-Joset, J., Leffler, J., Larcombe, Alexander, Stumbles, P., Robertson, S., Pasquali, C., Holt, P., and Strickland, D.

Abstract

Chronic allergic inflammatory diseases are a major cause of morbidity, with allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either the promotion or prevention of disease. Major reductions in asthma prevalence are documented in European and US farming communities. Protection is associated with exposure of mothers during pregnancy to microbial breakdown products present in farm dusts and unprocessed foods and enhancement of innate immune competence in the children. We sought to develop a scientific rationale for progressing these findings toward clinical application for primary disease prevention. Treatment of pregnant mice with a defined, clinically approved immune modulator was shown to markedly reduce susceptibility of their offspring to development of the hallmark clinical features of allergic airway inflammatory disease. Mechanistically, offspring displayed enhanced dendritic cell-dependent airway mucosal immune surveillance function, which resulted in more efficient generation of mucosal-homing regulatory T cells in response to local inflammatory challenge. We provide evidence that the principal target for maternal treatment effects was the fetal dendritic cell progenitor compartment, equipping the offspring for accelerated functional maturation of the airway mucosal dendritic cell network following birth. These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention.

Published
2018

41. 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

44. Surgical treatment of pancreatic endocrine tumours in Italy: results of a prospective multicentre study of 262 cases

Author

Zerbi, A, Capitanio, V, Boninsegna, L, Pasquali, C, Rindi, G, Delle Fave, G, Del Chiaro, M, Casadei, R, Falconi, M, Di Carlo V, Pederzoli P, Delle Fave G, Pedrazzoli S, Tomassetti P, Casadei R, Garcea D, Uomo G, Colangelo E, Mosca F, Fronda GR, Bresadola F, Cantore M, Leone BE, Farinati F, Toma SS, Luppi G, Bene A, Bajetta E, Ruffini L, Gebbia V, Liguori L, De Toma G, Dogliotti L, Massidda B, Zerbi, A, Capitanio, V, Boninsegna, L, Pasquali, C, Rindi, G, Delle Fave, G, Del Chiaro, M, Casadei, R, Falconi, M, Di Carlo, V, Pederzoli, P, Pedrazzoli, S, Tomassetti, P, Garcea, D, Uomo, G, Colangelo, E, Mosca, F, Fronda, G, Bresadola, F, Cantore, M, Leone, B, Farinati, F, Toma, S, Luppi, G, Bene, A, Bajetta, E, Ruffini, L, Gebbia, V, Liguori, L, De Toma, G, Dogliotti, L, Massidda, B, A., Zerbi, V., Capitanio, L., Boninsegna, C., Pasquali, G., Rindi, G. D., Fave, M. D., Chiaro, R., Casadei, Falconi, Massimo, A. I. S. P., Network Study Group, Zerbi A., Capitanio V., Boninsegna L., Pasquali C., Rindi G., Delle Fave G., Del Chiaro M., Casadei R., Falconi M., and AISP Network Study Group.

Subjects
Adult, Male, medicine.medical_specialty, Exploratory laparotomy, medicine.medical_treatment, Risk Assessment, Disease-Free Survival, pancreatic endocrine tumours, Pancreaticoduodenectomy, Pancreatectomy, medicine, Humans, Prospective Studies, Laparoscopy, Prospective cohort study, Aged, Neoplasm Staging, medicine.diagnostic_test, Settore MED/08 - ANATOMIA PATOLOGICA, business.industry, General surgery, Biopsy, Needle, Middle Aged, Debulking, endocrine, tumours,PET, Immunohistochemistry, Survival Analysis, Surgery, Pancreatic Neoplasms, Neuroendocrine Tumors, Treatment Outcome, Italy, Cardiothoracic surgery, Female, Neoplasm Recurrence, Local, business, PANCREATIC ENDOCRINE TUMOR, Abdominal surgery, Follow-Up Studies
Abstract

BACKGROUND: Information on the treatment of pancreatic endocrine tumours (PETs) comes mostly from small, retrospective, uncontrolled studies. METHODS: Newly diagnosed, histologically proven PETs, observed from June 2004 to March 2007 in 24 Italian centres, were included in a specific dataset. RESULTS: Three-hundred and ten patients (mean age 57.6 years, females 46.6%) were analysed. At the time of recruitment, 262 (84.5%) underwent surgery. The percentage of operated patients was 91.9% and 62.0% in surgical and non-surgical centres, respectively. A curative resection was carried out in 83.6% (n = 219) of cases, a palliative resection (debulking) in 10.7% (n = 28), an exploratory laparotomy in 4.6% (n = 12), and a bypass procedure in 1.1% (n = 3). Laparoscopy was performed in 8.0% (n = 21) of cases. Resection consisted of a pancreatoduodenectomy in 46 cases (21.0%), a distal pancreatectomy in 95 (43.4%), an enucleation in 50 (22.8%), a middle pancreatectomy in 16 (7.3%) and a total pancreatectomy in 12 (5.5%). Liver resection was associated with pancreatic resection in 26 cases (9.9%). Post-operative mortality was 1.5% and morbidity 39.7%, respectively. A curative resection was performed more frequently in asymptomatic, small, non-metastatic, benign and at uncertain behaviour tumours, with low Ki67 values. CONCLUSIONS: This study strongly indicates the fact that surgical resection represents the cornerstone treatment of PETs.

Published
2011

45. Clinicopathological features of pancreatic endocrine tumors: a prospective multicenter study in Italy of 297 sporadic cases

Author

Zerbi A, Falconi M, Rindi G, Delle Fave G, Tomassetti Casadei PR, Pasquali C, Di Carlo V, Capitanio V, Boninsegna L, Pederzoli P, Pedrazzoli S, Garcea D, Uomo G, Colangelo E, Mosca F, Fronda GR, Bresadola F, Cantore M, Farinati F, Leone BE, Toma SS, Luppi G, Bene A, Bajetta E, Ruffini L, Gebbia V, Liguori L, De Toma G, Dogliotti L, Massidda B., A., Zerbi, Falconi, Massimo, G., Rindi, G. D., Fave, P., Tomassetti, C., Pasquali, V., Capitanio, L., Boninsegna, V. D., Carlo, A. I. S. P., Network Study Group, Zerbi A, Falconi M, Rindi G, Delle Fave GF, Tomassetti P, Pasquali C, Capitanio V, Boninsegna L, Di Carlo V, and the members of the AISP-Network Study Group, Zerbi, A, Falconi, M, Rindi, G, Delle Fave, G, Tomassetti Casadei, P, Pasquali, C, Di Carlo, V, Capitanio, V, Boninsegna, L, Pederzoli, P, Pedrazzoli, S, Garcea, D, Uomo, G, Colangelo, E, Mosca, F, Fronda, G, Bresadola, F, Cantore, M, Farinati, F, Leone, B, Toma, S, Luppi, G, Bene, A, Bajetta, E, Ruffini, L, Gebbia, V, Liguori, L, De Toma, G, Dogliotti, L, and Massidda, B

Subjects
Adult, Male, medicine.medical_specialty, Pancreatic disease, Gastroenterology, Pancreatic tumor, Internal medicine, medicine, Carcinoma, Endocrine system, Humans, Prospective Studies, Prospective cohort study, Aged, Islet Cell, Female, Insulinoma, Italy, Middle Aged, Pancreatic Neoplasms, PANCREAS, Hepatology, business.industry, Pancreatic Neoplasm, medicine.disease, medicine.anatomical_structure, Multicenter study, Clinicopathological features, Carcinoma, Islet Cell, Pancreas, business, Human
Abstract

Objectives: Information on pancreatic endocrine tumors (PETs) comes mostly from small, retrospective, uncontrolled studies conducted on highly selected patients. The aim of the study was to describe the clinical and pathological features of PETs in a prospective, multicenter study.Methods: Newly diagnosed, histologically proven, sporadic PETs observed from June 2004 to March 2007 in 24 Italian centers were included in a specific data set.Results: Two hundred ninety-seven patients (mean age 58.614.7 years, females 51.2%, males 48.8%) were analyzed. In 73 cases (24.6%), the tumor was functioning (F) (53 insulinomas, 15 gastrinomas, 5 other syndromes) and in 232 (75.4%) it was non-functioning (NF); in 115 cases (38.7%), the diagnosis was incidental. The median tumor size was 20 mm (range 2-150). NF-PETs were significantly more represented among carcinomas (P0.001). Nodal and liver metastases were detected in 84 (28.3%) and 85 (28.6%) cases, respectively. The presence of liver metastases was significantly higher in the NF-PETs than in the F-PETs (32.1% vs. 17.8%; P0.05), and in the symptomatic than in the asymptomatic patients (34.6% vs. 19.1%; P

Published
2010

46. Common germline variants within the CDKN2A/2B region affect risk of pancreatic neuroendocrine tumors

Author

Campa, D. Capurso, G. Pastore, M. Talar-Wojnarowska, R. Milanetto, A.C. Landoni, L. Maiello, E. Lawlor, R.T. Malecka-Panas, E. Funel, N. Gazouli, M. De Bonis, A. Klüter, H. Rinzivillo, M. Delle Fave, G. Hackert, T. Landi, S. Bugert, P. Bambi, F. Archibugi, L. Scarpa, A. Katzke, V. Dervenis, C. Liço, V. Furlanello, S. Strobel, O. Tavano, F. Basso, D. Kaaks, R. Pasquali, C. Gentiluomo, M. Rizzato, C. Canzian, F.

Abstract

Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2.08, 95% CI 1.05-4.11, p = 0.035). This SNP is in linkage disequilibrium with another polymorphic variant associated with increased risk of several cancer types. In silico analysis suggested that the SNP could alter the sequence recognized by the Neuron-Restrictive Silencer Factor (NRSF), whose deregulation has been associated with the development of several tumors. The mechanistic link between the allele and the disease has not been completely clarified yet but the epidemiologic evidences that link the DNA region to increased cancer risk are convincing. In conclusion, our results suggest rs2518719 as a pleiotropic CDKN2A variant associated with the risk of developing PNETs. © 2016 The Author(s).

Published
2016

48. Functional single nucleotide polymorphisms within the cyclindependent kinase inhibitor 2A/2B region affect pancreatic cancer risk

Author

Campa, D. Pastore, M. Gentiluomo, M. Talar-Wojnarowska, R. Kupcinskas, J. Malecka-Panas, E. Neoptolemos, J.P. Niesen, W. Vodicka, P. Delle Fave, G. Bas Bueno-de-Mesquita, H. Gazouli, M. Pacetti, P. Di Leo, M. Ito, H. Klüter, H. Soucek, P. Corbo, V. Yamao, K. Hosono, S. Kaaks, R. Vashist, Y. Gioffreda, D. Strobel, O. Shimizu, Y. Dijk, F. Andriulli, A. Ivanauskas, A. Bugert, P. Tavano, F. Vodickova, L. Zambon, C.F. Lovecek, M. Landi, S. Key, T.J. Boggi, U. Pezzilli, R. Jamroziak, K. Mohelnikova-Duchonova, B. Mambrini, A. Bambi, F. Busch, O. Pazienza, V. Valente, R. Theodoropoulos, G.E. Hackert, T. Capurso, G. Cavestro, G.M. Pasquali, C. Basso, D. Sperti, C. Matsuo, K. Büchler, M. Khaw, K.-T. Izbicki, J. Costello, E. Katzke, V. Michalski, C. Stepien, A. Rizzato, C. Canzian, F.

Abstract

The CDKN2A (p16) gene plays a key role in pancreatic cancer etiology. It is one of the most commonly somatically mutated genes in pancreatic cancer, rare germline mutations have been found to be associated with increased risk of developing familiar pancreatic cancer and CDKN2A promoter hyper-methylation has been suggested to play a critical role both in pancreatic cancer onset and prognosis. In addition several unrelated SNPs in the 9p21.3 region, that includes the CDNK2A, CDNK2B and the CDNK2B-AS1 genes, are associated with the development of cancer in various organs. However, association between the common genetic variability in this region and pancreatic cancer risk is not clearly understood. We sought to fill this gap in a case-control study genotyping 13 single nucleotide polymorphisms (SNPs) in 2,857 pancreatic ductal adenocarcinoma (PDAC) patients and 6,111 controls in the context of the Pancreatic Disease Research (PANDoRA) consortium. We found that the A allele of the rs3217992 SNP was associated with an increased pancreatic cancer risk (ORhet=1.14, 95% CI 1.01-1.27, p=0.026, ORhom=1.30, 95% CI 1.12-1.51, p=0.00049). This pleiotropic variant is reported to be a mir-SNP that, by changing the binding site of one or more miRNAs, could influence the normal cell cycle progression and in turn increase PDAC risk. In conclusion, we observed a novel association in a pleiotropic region that has been found to be of key relevance in the susceptibility to various types of cancer and diabetes suggesting that the CDKN2A/B locus could represent a genetic link between diabetes and pancreatic cancer risk.

Published
2016

49. Association of genetic polymorphisms with survival of pancreatic ductal adenocarcinoma patients

Author

Rizzato, C. Campa, D. Talar-Wojnarowska, R. Halloran, C. Kupcinskas, J. Butturini, G. Mohelníková-Duchoňová, B. Sperti, C. Tjaden, C. Ghaneh, P. Hackert, T. Funel, N. Giese, N. Tavano, F. Pezzilli, R. Pedata, M. Pasquali, C. Gazouli, M. Mambrini, A. Souček, P. di Sebastiano, P. Capurso, G. Cantore, M. Oliverius, M. Offringa, R. Małecka-Panas, E. Strobel, O. Scarpa, A. Canzian, F.

Abstract

Germline genetic variability might contribute, at least partially, to the survival of pancreatic ductal adenocarcinoma (PDAC) patients. Two recently performed genome-wide association studies (GWAS) on PDAC overall survival (OS) suggested (P < 10-5) the association between 30 genomic regions and PDAC OS. With the aim to highlight the true associations within these regions, we analyzed 44 single-nucleotide polymorphisms (SNPs) in the 30 candidate regions in 1722 PDAC patients within the PANcreatic Disease ReseArch (PANDoRA) consortium. We observed statistically significant associations for five of the selected regions. One association in the CTNNA2 gene on chromosome 2p12 [rs1567532, hazard ratio (HR) = 1.75, 95% confidence interval (CI) 1.19-2.58, P = 0.005 for homozygotes for the minor allele] and one in the last intron of the RUNX2 gene on chromosome 6p21 (rs12209785, HR = 0.88, 95% CI 0.80-0.98, P = 0.014 for heterozygotes) are of particular relevance. These loci do not coincide with those that showed the strongest associations in the previous GWAS. In silico analysis strongly suggested a possible mechanistic link between these two SNPs and pancreatic cancer survival. Functional studies are warranted to confirm the link between these genes (or other genes mapping in those regions) and PDAC prognosis in order to understand whether these variants may have the potential to impact treatment decisions and design of clinical trials. © The Author 2016. Published by Oxford University Press. All rights reserved.

Published
2016

50. Protection against maternal infection-associated fetal growth restriction: proof-of-concept with a microbial-derived immunomodulator

Author

Scott, N.M., primary, Lauzon-Joset, J.F., additional, Jones, A.C., additional, Mincham, K.T., additional, Troy, N.M., additional, Leffler, J., additional, Serralha, M., additional, Prescott, S.L., additional, Robertson, S.A., additional, Pasquali, C., additional, Bosco, A., additional, Holt, P.G., additional, and Strickland, D.H., additional

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results