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Published in: Journal of Gastroenterology 8/2018

01-08-2018 | Original Article—Liver, Pancreas, and Biliary Tract

Statin use and pancreatic cancer risk in two prospective cohort studies

Authors: Tsuyoshi Hamada, Natalia Khalaf, Chen Yuan, Ana Babic, Vicente Morales-Oyarvide, Zhi Rong Qian, Jonathan Andrew Nowak, Kimmie Ng, Peter Kraft, Douglas Adam Rubinson, Meir Jonathan Stampfer, Edward Luciano Giovannucci, Charles Stewart Fuchs, Shuji Ogino, Brian Matthew Wolpin

Published in: Journal of Gastroenterology | Issue 8/2018

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Abstract

Background

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are common lipid-lowering agents and may reduce the risk of several cancer types including pancreatic cancer. However, the association between statin use and pancreatic cancer risk has not been fully evaluated in prospective studies.

Methods

We studied the association between statin use and incident pancreatic cancer in 113,059 participants from the prospective Nurses’ Health Study and Health Professionals Follow-up Study. Statin use was self-reported via study questionnaires and updated biennially. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of pancreatic cancer were estimated using multivariable Cox proportional hazards models with adjustment for potential confounders.

Results

In total, 583 participants developed incident pancreatic cancer during 1.4 million person-years of follow-up. No difference was identified in pancreatic cancer risk for regular versus non-regular statin users (multivariable-adjusted HR 0.98; 95% CI 0.82–1.16). There was no significant heterogeneity in the association of statin use with pancreatic cancer risk between the cohorts. Similarly, longer duration of regular statin use was not associated with decreased risk of pancreatic cancer (Ptrend = 0.65). The results remained similar when we examined statin use status at baseline or accounting for 4-year latency period. We observed no statistically significant effect modification for the association of statin use with pancreatic cancer risk by body mass index, smoking status, or diabetes mellitus status (all Pinteraction > 0.21).

Conclusions

Regular statin use was not associated with pancreatic cancer risk in two large prospective cohort studies in the U.S.
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Literature
2.
go back to reference Gazzerro P, Proto MC, Gangemi G, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012;64:102–46.CrossRefPubMed Gazzerro P, Proto MC, Gangemi G, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012;64:102–46.CrossRefPubMed
3.
go back to reference Demierre MF, Higgins PD, Gruber SB, et al. Statins and cancer prevention. Nat Rev Cancer. 2005;5:930–42.CrossRefPubMed Demierre MF, Higgins PD, Gruber SB, et al. Statins and cancer prevention. Nat Rev Cancer. 2005;5:930–42.CrossRefPubMed
4.
go back to reference Gronich N, Rennert G. Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol. 2013;10:625–42.CrossRefPubMed Gronich N, Rennert G. Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol. 2013;10:625–42.CrossRefPubMed
5.
go back to reference Pisanti S, Picardi P, Ciaglia E, et al. Novel prospects of statins as therapeutic agents in cancer. Pharmacol Res. 2014;88:84–98.CrossRefPubMed Pisanti S, Picardi P, Ciaglia E, et al. Novel prospects of statins as therapeutic agents in cancer. Pharmacol Res. 2014;88:84–98.CrossRefPubMed
6.
go back to reference Matusewicz L, Meissner J, Toporkiewicz M, et al. The effect of statins on cancer cells–review. Tumour Biol. 2015;36:4889–904.CrossRefPubMed Matusewicz L, Meissner J, Toporkiewicz M, et al. The effect of statins on cancer cells–review. Tumour Biol. 2015;36:4889–904.CrossRefPubMed
7.
go back to reference Mullen PJ, Yu R, Longo J, et al. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16:718–31.CrossRefPubMed Mullen PJ, Yu R, Longo J, et al. The interplay between cell signalling and the mevalonate pathway in cancer. Nat Rev Cancer. 2016;16:718–31.CrossRefPubMed
8.
9.
go back to reference Chen MJ, Tsan YT, Liou JM, et al. Statins and the risk of pancreatic cancer in type 2 diabetic patients—a population-based cohort study. Int J Cancer. 2016;138:594–603.CrossRefPubMed Chen MJ, Tsan YT, Liou JM, et al. Statins and the risk of pancreatic cancer in type 2 diabetic patients—a population-based cohort study. Int J Cancer. 2016;138:594–603.CrossRefPubMed
10.
go back to reference Carey FJ, Little MW, Pugh TF, et al. The differential effects of statins on the risk of developing pancreatic cancer: a case–control study in two centres in the United Kingdom. Dig Dis Sci. 2013;58:3308–12.CrossRefPubMed Carey FJ, Little MW, Pugh TF, et al. The differential effects of statins on the risk of developing pancreatic cancer: a case–control study in two centres in the United Kingdom. Dig Dis Sci. 2013;58:3308–12.CrossRefPubMed
11.
go back to reference Khurana V, Sheth A, Caldito G, et al. Statins reduce the risk of pancreatic cancer in humans: a case–control study of half a million veterans. Pancreas. 2007;34:260–5.CrossRefPubMed Khurana V, Sheth A, Caldito G, et al. Statins reduce the risk of pancreatic cancer in humans: a case–control study of half a million veterans. Pancreas. 2007;34:260–5.CrossRefPubMed
12.
go back to reference Cui X, Xie Y, Chen M, et al. Statin use and risk of pancreatic cancer: a meta-analysis. Cancer Causes Control. 2012;23:1099–111.CrossRefPubMed Cui X, Xie Y, Chen M, et al. Statin use and risk of pancreatic cancer: a meta-analysis. Cancer Causes Control. 2012;23:1099–111.CrossRefPubMed
13.
go back to reference Birmann BM, Barnard ME, Bertrand KA, et al. Nurses’ health study contributions on the epidemiology of less common cancers: endometrial, ovarian, pancreatic, and hematologic. Am J Public Health. 2016;106:1608–15.CrossRefPubMedPubMedCentral Birmann BM, Barnard ME, Bertrand KA, et al. Nurses’ health study contributions on the epidemiology of less common cancers: endometrial, ovarian, pancreatic, and hematologic. Am J Public Health. 2016;106:1608–15.CrossRefPubMedPubMedCentral
14.
go back to reference Giovannucci E, Ascherio A, Rimm EB, et al. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med. 1995;122:327–34.CrossRefPubMed Giovannucci E, Ascherio A, Rimm EB, et al. Physical activity, obesity, and risk for colon cancer and adenoma in men. Ann Intern Med. 1995;122:327–34.CrossRefPubMed
15.
16.
go back to reference Bao Y, Ng K, Wolpin BM, et al. Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer. 2010;102:1422–7.CrossRefPubMedPubMedCentral Bao Y, Ng K, Wolpin BM, et al. Predicted vitamin D status and pancreatic cancer risk in two prospective cohort studies. Br J Cancer. 2010;102:1422–7.CrossRefPubMedPubMedCentral
18.
go back to reference Rich-Edwards JW, Corsano KA, Stampfer MJ. Test of the National Death Index and Equifax Nationwide Death Search. Am J Epidemiol. 1994;140:1016–9.CrossRefPubMed Rich-Edwards JW, Corsano KA, Stampfer MJ. Test of the National Death Index and Equifax Nationwide Death Search. Am J Epidemiol. 1994;140:1016–9.CrossRefPubMed
19.
go back to reference Lee JE, Baba Y, Ng K, et al. Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies. Cancer Prev Res (Phila). 2011;4:1808–15.CrossRef Lee JE, Baba Y, Ng K, et al. Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies. Cancer Prev Res (Phila). 2011;4:1808–15.CrossRef
20.
go back to reference Tsai CJ, Leitzmann MF, Willett WC, et al. Statin use and the risk of cholecystectomy in women. Gastroenterology. 2009;136:1593–600.CrossRefPubMed Tsai CJ, Leitzmann MF, Willett WC, et al. Statin use and the risk of cholecystectomy in women. Gastroenterology. 2009;136:1593–600.CrossRefPubMed
21.
22.
go back to reference Chen Y, Wu F, Saito E, et al. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia. 2017;60:1022–32.CrossRefPubMedPubMedCentral Chen Y, Wu F, Saito E, et al. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia. 2017;60:1022–32.CrossRefPubMedPubMedCentral
23.
go back to reference Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRef Cochran WG. The combination of estimates from different experiments. Biometrics. 1954;10:101–29.CrossRef
24.
25.
go back to reference Fendrich V, Sparn M, Lauth M, et al. Simvastatin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Pancreatology. 2013;13:502–7.CrossRefPubMed Fendrich V, Sparn M, Lauth M, et al. Simvastatin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Pancreatology. 2013;13:502–7.CrossRefPubMed
26.
go back to reference Liao J, Chung YT, Yang AL, et al. Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice. Mol Carcinog. 2013;52:739–50.CrossRefPubMed Liao J, Chung YT, Yang AL, et al. Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice. Mol Carcinog. 2013;52:739–50.CrossRefPubMed
27.
28.
go back to reference Mohammed A, Qian L, Janakiram NB, et al. Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice. Int J Cancer. 2012;131:1951–62.CrossRefPubMedPubMedCentral Mohammed A, Qian L, Janakiram NB, et al. Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice. Int J Cancer. 2012;131:1951–62.CrossRefPubMedPubMedCentral
29.
go back to reference Corcos L, Le Jossic-Corcos C. Statins: perspectives in cancer therapeutics. Dig Liver Dis. 2013;45:795–802.CrossRefPubMed Corcos L, Le Jossic-Corcos C. Statins: perspectives in cancer therapeutics. Dig Liver Dis. 2013;45:795–802.CrossRefPubMed
30.
go back to reference Thurnher M, Nussbaumer O, Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents. Clin Cancer Res. 2012;18:3524–31.CrossRefPubMed Thurnher M, Nussbaumer O, Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents. Clin Cancer Res. 2012;18:3524–31.CrossRefPubMed
31.
go back to reference Jacobs EJ, Newton CC, Thun MJ, et al. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res. 2011;71:1763–71.CrossRefPubMed Jacobs EJ, Newton CC, Thun MJ, et al. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res. 2011;71:1763–71.CrossRefPubMed
32.
go back to reference Simon MS, Desai P, Wallace R, et al. Prospective analysis of association between statins and pancreatic cancer risk in the Women’s Health Initiative. Cancer Causes Control. 2016;27:415–23.CrossRefPubMedPubMedCentral Simon MS, Desai P, Wallace R, et al. Prospective analysis of association between statins and pancreatic cancer risk in the Women’s Health Initiative. Cancer Causes Control. 2016;27:415–23.CrossRefPubMedPubMedCentral
33.
go back to reference Jeon CY, Pandol SJ, Wu B, et al. The association of statin use after cancer diagnosis with survival in pancreatic cancer patients: a SEER-Medicare analysis. PLoS One. 2015;10:e0121783.CrossRefPubMedPubMedCentral Jeon CY, Pandol SJ, Wu B, et al. The association of statin use after cancer diagnosis with survival in pancreatic cancer patients: a SEER-Medicare analysis. PLoS One. 2015;10:e0121783.CrossRefPubMedPubMedCentral
34.
go back to reference Wu BU, Chang J, Jeon CY, et al. Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer. Am J Gastroenterol. 2015;110:1233–9.CrossRefPubMedPubMedCentral Wu BU, Chang J, Jeon CY, et al. Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer. Am J Gastroenterol. 2015;110:1233–9.CrossRefPubMedPubMedCentral
35.
go back to reference Gbelcova H, Lenicek M, Zelenka J, et al. Differences in antitumor effects of various statins on human pancreatic cancer. Int J Cancer. 2008;122:1214–21.CrossRefPubMed Gbelcova H, Lenicek M, Zelenka J, et al. Differences in antitumor effects of various statins on human pancreatic cancer. Int J Cancer. 2008;122:1214–21.CrossRefPubMed
36.
go back to reference Huang BZ, Chang JI, Li E, et al. Influence of statins and cholesterol on mortality among patients with pancreatic cancer. J Natl Cancer Inst. 2017;109:djw275.CrossRef Huang BZ, Chang JI, Li E, et al. Influence of statins and cholesterol on mortality among patients with pancreatic cancer. J Natl Cancer Inst. 2017;109:djw275.CrossRef
37.
go back to reference Lee HS, Lee SH, Lee HJ, et al. Statin use and its impact on survival in pancreatic cancer patients. Med (Baltimore). 2016;95:e3607.CrossRef Lee HS, Lee SH, Lee HJ, et al. Statin use and its impact on survival in pancreatic cancer patients. Med (Baltimore). 2016;95:e3607.CrossRef
Metadata
Title
Statin use and pancreatic cancer risk in two prospective cohort studies
Authors
Tsuyoshi Hamada
Natalia Khalaf
Chen Yuan
Ana Babic
Vicente Morales-Oyarvide
Zhi Rong Qian
Jonathan Andrew Nowak
Kimmie Ng
Peter Kraft
Douglas Adam Rubinson
Meir Jonathan Stampfer
Edward Luciano Giovannucci
Charles Stewart Fuchs
Shuji Ogino
Brian Matthew Wolpin
Publication date
01-08-2018
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 8/2018
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-018-1430-x

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