Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk

被引：7

作者：

Peduzzi, Giulia ^{[1
]}

Gentiluomo, Manuel ^{[1
]}

Tavano, Francesca ^{[23
]}

Arcidiacono, Paolo Giorgio ^{[3
]}

Ermini, Stefano ^{[4
]}

Vodicka, Pavel ^{[5
,6
,7
]}

Boggi, Ugo ^{[8
]}

Cavestro, Giulia Martina ^{[9
]}

Capurso, Gabriele ^{[3
,10
]}

Morelli, Luca ^{[11
]}

Milanetto, Anna Caterina ^{[12
]}

Pezzilli, Raffaele ^{[13
]}

Lawlor, Rita T. ^{[14
]}

Carrara, Silvia ^{[15
]}

Lovecek, Martin ^{[16
]}

Souc, Pavel ^{[17
]}

Guo, Feng ^{[18
]}

Hackert, Thilo ^{[19
]}

Uzunoglu, Faik G. ^{[20
]}

Gazouli, Maria ^{[21
]}

Parniczky, Andrea ^{[22
,23
]}

Kupcinskas, Juozas ^{[24
,25
]}

Bijlsma, Maarten F. ^{[26
]}

Bueno-de-Mesquita, Bas ^{[27
]}

Vermeulen, Roel ^{[28
]}

van Eijck, Casper H. J. ^{[29
]}

Jamroziak, Krzysztof ^{[30
]}

Talar-Wojnarowska, Renata ^{[31
]}

Greenhalf, William ^{[32
]}

Gioffreda, Domenica ^{[2
]}

Petrone, Maria C. ^{[3
]}

Landi, Stefano ^{[1
]}

Archibugi, Livia ^{[3
,10
]}

Puzzono, Marta ^{[9
,33
]}

Funel, Niccola ^{[34
]}

Sperti, Cosimo ^{[35
]}

Piredda, Maria L. ^{[14
]}

Mohelnikova-Duchonova, Beatrice ^{[36
]}

Lu, Ye ^{[37
,38
]}

Hlavac, Viktor ^{[17
]}

Gao, Xin ^{[18
,39
]}

Schneider, Martin ^{[19
]}

Izbicki, Jakob R. ^{[20
]}

Theodoropoulos, George ^{[40
]}

Bunduc, Stefania ^{[22
,41
]}

Kreivenaite, Edita ^{[24
,25
]}

Busch, Olivier R. ^{[42
]}

Malecka-Panas, Ewa ^{[31
]}

Costello, Eithne ^{[32
]}

Perri, Francesco ^{[2
]}

机构：

[1] Univ Pisa, Dept Biol, Via Luca Ghini, I-1356126 Pisa, Italy

[2] Fdn IRCCS Casa Sollievo Sofferenza Hosp, Div Gastroenterol & Res Lab, San Giovanni Rotondo, Italy

[3] IRCCS San Raffaele Sci Inst, Pancreatobiliary Endoscopy & Endosonog Div, Pancreas Translat & Clin Res Ctr, Milan, Italy

[4] Azienda Osped Univ Meyer, Childrens Hosp, Transfus Serv, Florence, Italy

[5] Charles Univ Prague, Inst Biol & Med Genet, Med Fac 1, Prague, Czech Republic

[6] Gen Univ Hosp, Prague, Czech Republic

[7] Czech Acad Sci, Inst Expt Med, Prague, Czech Republic

[8] Pisa Univ Hosp, Div Gen & Transplant Surg, Pisa, Italy

[9] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Gastroenterol & Gastrointestinal Endoscopy Unit, Milan, Italy

[10] Sapienza Univ Rome, St Andrea Univ Hosp, Fac Med & Psychol, Digest & Liver Dis Unit, Rome, Italy

[11] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Gen Surg Unit, Pisa, Italy

[12] Univ Padua, Clin Chirurg 1, Dept DISCOG, Padua, Italy

[13] San Carlo Hosp, Gastroenterol Unit, Potenza, Italy

[14] Univ & Hosp Trust Verona, Ctr Appl Res Canc, ARC NET, Verona, Italy

[15] IRCCS Humanitas Res Hosp, Dept Gastroenterol, Endoscop Unit, Milan, Italy

[16] Univ Hosp Olomouc, Dept Surg 1, Olomouc, Czech Republic

[17] Charles Univ Prague, Fac Med Pilsen, Biomed Ctr, Plzen, Czech Republic

[18] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[19] Univ Hosp Heidelberg, Dept Gen Visceral & Transplantat Surg, Heidelberg, Germany

[20] Univ Med Hamburg Eppendorf, Dept Gen Visceral & Thorac Surg, Hamburg, Germany

[21] Natl & Kapodistrian Univ Athens, Med Sch, Lab Biol, Athens, Greece

[22] Univ Pecs, Med Sch, Inst Translat Med, Pecs, Hungary

[23] Pal Heim Natl Inst Pediat, Budapest, Hungary

[24] Lithuanian Univ Hlth Sci, Gastroenterol Dept, Kaunas, Lithuania

[25] Lithuanian Univ Hlth Sci, Inst Digest Res, Kaunas, Lithuania

[26] Univ Amsterdam, Amsterdam Univ Med Ctr, Canc Ctr Amsterdam, Lab Expt Oncol & Radiobiol, Amsterdam, Netherlands

[27] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands

[28] Univ Utrecht, Utrecht, Netherlands

[29] Erasmus Univ, Erasmus Med Ctr, Dept Surg, Rotterdam, Netherlands

[30] Med Univ Warsaw, Dept Hematol Transplantat & Internal Med, Warsaw, Poland

[31] Med Univ Lodz, Dept Digest Tract Dis, Lodz, Poland

[32] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside, England

[33] Univ Siena, Dept Med Biotechnol, Siena, Italy

[34] Pisa Univ Hosp, Unit Expt Surg Pathol, Dept Surg, Pisa, Italy

[35] Univ Padua, Clin Chirurg 3, Dept DISCOG, Padua, Italy

[36] Palacky Univ Olomouc, Fac Med & Dent, Dept Oncol, Olomouc, Czech Republic

[37] German Canc Res Ctr, Genom Epidemiol Res Grp, Heidelberg, Germany

[38] Heidelberg Univ, Med Fac Heidelberg, Heidelberg, Germany

[39] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[40] Natl & Kapodistrian Univ Athens, Propaedeut Univ Surg Clin 1, Sch Med, Hippocratio Gen Hosp, Athens, Greece

[41] Fundeni Clin Inst, Bucharest, Romania

[42] Amsterdam Univ Med Ctr, Canc Ctr Amsterdam, Dept Surg, Amsterdam, Netherlands

[43] Charles Univ Prague, Univ Hosp Kralovske Vinohrady, Fac Med 3, Dept Surg, Prague, Czech Republic

[44] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany

[45] Natl Ctr Tumor Dis NCT, Heidelberg, Germany

[46] Fdn IRCCS Casa Sollievo Sofferenza Hosp, Dept Oncol, San Giovanni Rotondo, Italy

[47] Univ Szeged, Dept Med, Ctr Translat Med, Szeged, Hungary

[48] Fdn IRCCS Casa Sollievo Sofferenza Hosp, Dept Surg Sci, San Giovanni Rotondo, Italy

[49] Univ Padua, Dept DIMED, Padua, Italy

来源：

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION | 2021年 / 30卷 / 12期

关键词：

GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY;

D O I：

10.1158/1055-9965.EPI-21-0353

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk (P < 0.05). In the second phase, none of the findings were replicated. In the gene-level analysis, we observed that three genes (TERT, SUGCT, and SURF1) involved in the mitochondrial metabolism showed an association below the Bonferroni-corrected threshold of statistical significance (P = 0.05/1588 - 3.1 x 10(-5)). Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk.

引用

页码：2342 / 2345

页数：4

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