Generic placeholder image

Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Research Article

The Causal Effects of Cholelithiasis on Acute Pancreatitis and Pancreatic Cancer: A Large Sample Size Mendelian Randomization Analysis

Author(s): Moshi Rao, Xiaoshun Ai and Zijian Huang*

Volume 19, Issue 1, 2024

Published on: 26 June, 2023

Page: [72 - 79] Pages: 8

DOI: 10.2174/1574892818666230609121409

Price: $65

Abstract

Background: The aim of two-sample Mendelian randomization (MR) with a large sample size was to explore the causal cholelithiasis impact on acute pancreatitis and pancreatic cancer.

Methods: We performed the two-sample MR analysis with two models. Publicly available summary- level information for cholelithiasis was acquired from the Genome-Wide Summary Association Studies (GWAS) of FinnGen Biobank. The inverse variance weighted (IVW) method was the main method to obtain the MR estimates. Other methods were also used as supplementary methods, including MR-Egger, maximum likelihood, MR-Robust Adjusted Profile Score (MR-RAPS), weighted median, penalised weighted median method, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method.

Results: After the selection of genetic instrumental variables (IVs), 11 single nucleotide polymorphisms (SNPs) (Model 1) and 22 SNPs (Model 2) were used to explore the effect of cholelithiasis on acute pancreatitis, and 10 SNPs (Model 1) and 24 SNPs (Model 2) on pancreatic cancer. The findings obtained by the fixed-effect IVW method with both Model 1 and Model 2 showed that genetically predicted cholelithiasis was significantly related to the elevated acute pancreatitis risk (Model 1: OR: 1.001, 95% CI: 1.000-1.002, p <0.001; Model 2: OR: 1.001, 95% CI: 1.000-1.002, p <0.001). Moreover, cholelithiasis would also raise the pancreatic cancer risk (Model 1: OR: 1.676, 95% CI: 1.228-2.288, p = 0.001; Model 2: OR: 1.432, 95% CI: 1.116-1.839, p = 0.005).

Conclusion: Genetically predicted cholelithiasis was significantly related to the elevated risk of acute pancreatitis and pancreatic cancer. More attention should be paid to patients with cholelithiasis for the primary prevention of pancreatic-related diseases.

Keywords: Cholelithiasis, acute pancreatitis, pancreatic cancer, mendelian randomization, large sample size, IVW method.

[1]
Lankisch PG, Apte M, Banks PA. Acute pancreatitis. Lancet 2015; 386(9988): 85-96.
[http://dx.doi.org/10.1016/S0140-6736(14)60649-8] [PMID: 25616312]
[2]
Boxhoorn L, Voermans RP, Bouwense SA, et al. Acute pancreatitis. Lancet 2020; 396(10252): 726-34.
[http://dx.doi.org/10.1016/S0140-6736(20)31310-6] [PMID: 32891214]
[3]
Szatmary P, Grammatikopoulos T, Cai W, et al. Acute pancreatitis: Diagnosis and treatment. Drugs 2022; 82(12): 1251-76.
[http://dx.doi.org/10.1007/s40265-022-01766-4] [PMID: 36074322]
[4]
Klein AP. Pancreatic cancer epidemiology: Understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol 2021; 18(7): 493-502.
[http://dx.doi.org/10.1038/s41575-021-00457-x] [PMID: 34002083]
[5]
Mederos MA, Reber HA, Girgis MD. Acute pancreatitis. JAMA 2021; 325(4): 382-90.
[http://dx.doi.org/10.1001/jama.2020.20317] [PMID: 33496779]
[6]
Zhou Y, Zhou Q, Lin Q, et al. Evaluation of risk factors for extrahepatic cholangiocarcinoma: ABO blood group, hepatitis B virus and their synergism. Int J Cancer 2013; 133(8): 1867-75.
[http://dx.doi.org/10.1002/ijc.28196] [PMID: 23564396]
[7]
Tanaja J, Lopez RA, Meer JM. Cholelithiasis. Treasure Island, FL: StatPearls Publishing LLC 2022.
[8]
Dzieniszewski GP, Neher M, Schmidt H-D, Kümmerle F. Cholelithiasis und akute Pankreatitis. Dtsch Med Wochenschr 1984; 109(36): 1349-55.
[http://dx.doi.org/10.1055/s-2008-1069376] [PMID: 6468298]
[9]
Gong Y, Li S, Tang Y, et al. Cholelithiasis and risk of pancreatic cancer: Systematic review and meta-analysis of 21 observational studies. Cancer Causes Control 2014; 25(11): 1543-51.
[http://dx.doi.org/10.1007/s10552-014-0458-3] [PMID: 25146444]
[10]
Fan Y, Hu J, Feng B, et al. Increased risk of pancreatic cancer related to gallstones and cholecystectomy: A systematic review and meta-analysis. Pancreas 2016; 45(4): 503-9.
[http://dx.doi.org/10.1097/MPA.0000000000000502] [PMID: 26684857]
[11]
Libuda L, Laabs B-H, Ludwig C, et al. Vitamin D and the risk of depression: A causal relationship? findings from a mendelian randomization study. Nutrients 2019; 11(5): 1085.
[http://dx.doi.org/10.3390/nu11051085] [PMID: 31100827]
[12]
Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA 2017; 318(19): 1925-6.
[http://dx.doi.org/10.1001/jama.2017.17219] [PMID: 29164242]
[13]
Burgess S, Foley CN, Allara E, Staley JR, Howson JMM. A robust and efficient method for Mendelian randomization with hundreds of genetic variants. Nat Commun 2020; 11(1): 376.
[http://dx.doi.org/10.1038/s41467-019-14156-4] [PMID: 31953392]
[14]
Rusk N. The UK Biobank. Nat Methods 2018; 15(12): 1001.
[http://dx.doi.org/10.1038/s41592-018-0245-2] [PMID: 30504882]
[15]
Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 2009; 41(9): 986-90.
[http://dx.doi.org/10.1038/ng.429] [PMID: 19648918]
[16]
Hartwig FP, Borges MC, Horta BL, Bowden J, Davey SG. Inflammatory biomarkers and risk of schizophrenia: A 2-sample mendelian randomization study. JAMA Psychiatry 2017; 74(12): 1226-33.
[http://dx.doi.org/10.1001/jamapsychiatry.2017.3191] [PMID: 29094161]
[17]
Park S, Lee S, Kim Y, et al. Atrial fibrillation and kidney function: A bidirectional Mendelian randomization study. Eur Heart J 2021; 42(29): 2816-23.
[http://dx.doi.org/10.1093/eurheartj/ehab291] [PMID: 34023889]
[18]
Burgess S, Thompson SG. Multivariable Mendelian randomization: The use of pleiotropic genetic variants to estimate causal effects. Am J Epidemiol 2015; 181(4): 251-60.
[http://dx.doi.org/10.1093/aje/kwu283] [PMID: 25632051]
[19]
Birney E. Mendelian randomization. Cold Spring Harb Perspect Med 2022; 12(4): a041302.
[PMID: 34872952]
[20]
Lee PJ, Papachristou GI. New insights into acute pancreatitis. Nat Rev Gastroenterol Hepatol 2019; 16(8): 479-96.
[http://dx.doi.org/10.1038/s41575-019-0158-2] [PMID: 31138897]
[21]
Pierce BL, Burgess S. Efficient design for Mendelian randomization studies: Subsample and 2-sample instrumental variable estimators. Am J Epidemiol 2013; 178(7): 1177-84.
[http://dx.doi.org/10.1093/aje/kwt084] [PMID: 23863760]
[22]
Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 2016; 40(4): 304-14.
[http://dx.doi.org/10.1002/gepi.21965] [PMID: 27061298]
[23]
Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from mendelian randomization analyses with multiple genetic variants. Epidemiology 2017; 28(1): 30-42.
[http://dx.doi.org/10.1097/EDE.0000000000000559] [PMID: 27749700]
[24]
Hartwig FP, Davey SG, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol 2017; 46(6): 1985-98.
[http://dx.doi.org/10.1093/ije/dyx102] [PMID: 29040600]
[25]
Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. Int J Epidemiol 2015; 44(2): 512-25.
[http://dx.doi.org/10.1093/ije/dyv080] [PMID: 26050253]
[26]
Fu Y, Xu F, Jiang L, et al. Circulating vitamin C concentration and risk of cancers: A Mendelian randomization study. BMC Med 2021; 19(1): 171.
[http://dx.doi.org/10.1186/s12916-021-02041-1] [PMID: 34325683]
[27]
Choi KW, Chen C-Y, Stein MB, et al. Assessment of bidirectional relationships between physical activity and depression among adults: A 2-sample mendelian randomization study. JAMA Psychiatry 2019; 76(4): 399-408.
[http://dx.doi.org/10.1001/jamapsychiatry.2018.4175] [PMID: 30673066]
[28]
Wang CC, Tseng M-H, Wu S-W, et al. Symptomatic cholelithiasis patients have an increased risk of pancreatic cancer: A population-based study. J Gastroenterol Hepatol 2021; 36(5): 1187-96.
[http://dx.doi.org/10.1111/jgh.15234] [PMID: 32881083]
[29]
Zhang J, Prizment AE, Dhakal IB, Anderson KE. Cholecystectomy, gallstones, tonsillectomy, and pancreatic cancer risk: A population-based case-control study in Minnesota. Br J Cancer 2014; 110(9): 2348-53.
[http://dx.doi.org/10.1038/bjc.2014.154] [PMID: 24667646]
[30]
Zhao X, Wang N, Sun Y, et al. Screen-detected gallstone disease and risk of liver and pancreatic cancer: The Kailuan Cohort Study. Liver Int 2020; 40(7): 1744-55.
[http://dx.doi.org/10.1111/liv.14456] [PMID: 32250535]
[31]
Acosta JM, Ledesma CL. Gallstone migration as a cause of acute pancreatitis. N Engl J Med 1974; 290(9): 484-7.
[http://dx.doi.org/10.1056/NEJM197402282900904] [PMID: 4810815]
[32]
Spanier BWM, Dijkgraaf MGW, Bruno MJ. Epidemiology, aetiology and outcome of acute and chronic pancreatitis: An update. Best Pract Res Clin Gastroenterol 2008; 22(1): 45-63.
[http://dx.doi.org/10.1016/j.bpg.2007.10.007] [PMID: 18206812]
[33]
Wang GJ, Gao C-F, Wei D, Wang C, Ding S-Q. Acute pancreatitis: Etiology and common pathogenesis. World J Gastroenterol 2009; 15(12): 1427-30.
[http://dx.doi.org/10.3748/wjg.15.1427] [PMID: 19322914]
[34]
Diehl AK, Holleman DR Jr, Chapman JB, Schwesinger WH, Kurtin WE. Gallstone size and risk of pancreatitis. Arch Intern Med 1997; 157(15): 1674-8.
[http://dx.doi.org/10.1001/archinte.1997.00440360088009] [PMID: 9250228]
[35]
Gardner TB. Acute pancreatitis. Ann Intern Med 2021; 174(2): ITC17-32.
[http://dx.doi.org/10.7326/AITC202102160] [PMID: 33556276]
[36]
Smith GD, Ebrahim S. ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol 2003; 32(1): 1-22.
[http://dx.doi.org/10.1093/ije/dyg070] [PMID: 12689998]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy