Statins and pancreatic cancer (Review)
- Authors:
- Jun Gong
- Esha Sachdev
- Lori A. Robbins
- Emily Lin
- Andrew E. Hendifar
- Monica M. Mita
-
Affiliations: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA, Department of Internal Medicine, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA, Department of Internal Medicine, Harbor‑UCLA Medical Center, Torrance, CA 90509, USA, Department of Internal Medicine, Division of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA, Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA - Published online on: January 4, 2017 https://doi.org/10.3892/ol.2017.5572
- Pages: 1035-1040
This article is mentioned in:
Abstract
Howlader N, Noone AM, Krapcho M, Garshell J, Neyman N, Altekruse SF, et al: SEER Cancer Statistics Review, 1975–2011. National Cancer Institute; Bethesda, MD: http://seer.cancer.gov/csr/1975_2011/2014 | |
Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI | |
Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI | |
Ryan DP, Hong TS and Bardeesy N: Pancreatic adenocarcinoma. N Engl J Med. 371:1039–1049. 2014. View Article : Google Scholar : PubMed/NCBI | |
Hidalgo M: Pancreatic cancer. N Engl J Med. 362:1605–1617. 2010. View Article : Google Scholar : PubMed/NCBI | |
Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK and Hruban RH: Recent progress in pancreatic cancer. CA Cancer J Clin. 63:318–348. 2013. View Article : Google Scholar : PubMed/NCBI | |
Lowenfels AB and Maisonneuve P: Can we prevent pancreatic disease? Clin Gastroenterol Hepatol. 12:1645–1646. 2014. View Article : Google Scholar : PubMed/NCBI | |
Alsamarrai A, Das SL, Windsor JA and Petrov MS: Factors that affect risk for pancreatic disease in the general population: A systematic review and meta-analysis of prospective cohort studies. Clin Gastroenterol Hepatol. 12:1635.e5–1644.e5; quiz e103. 2014. View Article : Google Scholar | |
Maisonneuve P and Lowenfels AB: Risk factors for pancreatic cancer: A summary review of meta-analytical studies. Int J Epidemiol. 44:186–198. 2015. View Article : Google Scholar : PubMed/NCBI | |
Gronich N and Rennert G: Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol. 10:625–642. 2013. View Article : Google Scholar : PubMed/NCBI | |
Rosato V, Tavani A, Bosetti C, Pelucchi C, Talamini R, Polesel J, Serraino D, Negri E and La Vecchia C: Metabolic syndrome and pancreatic cancer risk: A case-control study in Italy and meta-analysis. Metabolism. 60:1372–1378. 2011. View Article : Google Scholar : PubMed/NCBI | |
Esposito K, Chiodini P, Colao A, Lenzi A and Giugliano D: Metabolic syndrome and risk of cancer: A systematic review and meta-analysis. Diabetes Care. 35:2402–2411. 2012. View Article : Google Scholar : PubMed/NCBI | |
Stocks T, Bjørge T, Ulmer H, Manjer J, Häggström C, Nagel G, Engeland A, Johansen D, Hallmans G, Selmer R, et al: Metabolic risk score and cancer risk: Pooled analysis of seven cohorts. Int J Epidemiol. 44:1353–1363. 2015. View Article : Google Scholar : PubMed/NCBI | |
Gong J, Robbins LA, Lugea A, Waldron RT, Jeon CY and Pandol SJ: Diabetes, pancreatic cancer, and metformin therapy. Front Physiol. 5:4262014. View Article : Google Scholar : PubMed/NCBI | |
de Gonzalez A Berrington, Sweetland S and Spencer E: A meta-analysis of obesity and the risk of pancreatic cancer. Br J Cancer. 89:519–523. 2003. View Article : Google Scholar : PubMed/NCBI | |
Larsson SC, Orsini N and Wolk A: Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies. Int J Cancer. 120:1993–1998. 2007. View Article : Google Scholar : PubMed/NCBI | |
Arslan AA, Helzlsouer KJ, Kooperberg C, Shu XO, Steplowski E, Bueno-de-Mesquita HB, Fuchs CS, Gross MD, Jacobs EJ, Lacroix AZ, et al: Anthropometric measures, body mass index and pancreatic cancer: A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch Intern Med. 170:791–802. 2010. View Article : Google Scholar : PubMed/NCBI | |
Jiao L, de Gonzalez A Berrington, Hartge P, Pfeiffer RM, Park Y, Freedman DM, Gail MH, Alavanja MC, Albanes D, Freeman LE Beane, et al: Body mass index, effect modifiers, and risk of pancreatic cancer: A pooled study of seven prospective cohorts. Cancer Causes Control. 21:1305–1314. 2010. View Article : Google Scholar : PubMed/NCBI | |
Genkinger JM, Spiegelman D, Anderson KE, Bernstein L, van den Brandt PA, Calle EE, English DR, Folsom AR, Freudenheim JL, Fuchs CS, et al: A pooled analysis of 14 cohort studies of anthropometric factors and pancreatic cancer risk. Int J Cancer. 129:1708–1717. 2011. View Article : Google Scholar : PubMed/NCBI | |
Aune D, Greenwood DC, Chan DS, Vieira R, Vieira AR, Rosenblatt DA Navarro, Cade JE, Burley VJ and Norat T: Body mass index, abdominal fatness and pancreatic cancer risk: A systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol. 23:843–852. 2012. View Article : Google Scholar : PubMed/NCBI | |
Bethea TN, Kitahara CM, Sonderman J, Patel AV, Harvey C, Knutsen SF, Park Y, Park SY, Fraser GE, Jacobs EJ, et al: A pooled analysis of body mass index and pancreatic cancer mortality in African Americans. Cancer Epidemiol Biomarkers Prev. 23:2119–2125. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lin Y, Fu R, Grant E, Chen Y, Lee JE, Gupta PC, Ramadas K, Inoue M, Tsugane S, Gao YT, et al: Association of body mass index and risk of death from pancreatic cancer in Asians: Findings from the Asia Cohort Consortium. Eur J Cancer Prev. 22:224–250. 2013. View Article : Google Scholar | |
Hori M, Takahashi M, Hiraoka N, Yamaji T, Mutoh M, Ishigamori R, Furuta K, Okusaka T, Shimada K, Kosuge T, et al: Association of pancreatic fatty infiltration with pancreatic ductal adenocarcinoma. Clin Transl Gastroenterol. 5:e532014. View Article : Google Scholar : PubMed/NCBI | |
Rebours V, Gaujoux S, d'Assignies G, Sauvanet A, Ruszniewski P, Levy P, Bedossa P, Paradis V and Couvelard A: Obesity and fatty pancreatic infiltration are risk factors for pancreatic precancerous lesions (PanIN). Clin Cancer Res. 21:3522–3528. 2015. View Article : Google Scholar : PubMed/NCBI | |
Bao Y, Giovannucci EL, Kraft P, Stampfer MJ, Ogino S, Ma J, Buring JE, Sesso HD, Lee IM, Gaziano JM, et al: A prospective study of plasma adiponectin and pancreatic cancer risk in five US cohorts. J Natl Cancer Inst. 105:95–103. 2013. View Article : Google Scholar : PubMed/NCBI | |
Bao Y and Michaud DS: Physical activity and pancreatic cancer risk: A systematic review. Cancer Epidemiol Biomarkers Prev. 17:2671–2682. 2008. View Article : Google Scholar : PubMed/NCBI | |
O'Rorke MA, Cantwell MM, Cardwell CR, Mulholland HG and Murray LJ: Can physical activity modulate pancreatic cancer risk? a systematic review and meta-analysis. Int J Cancer. 126:2957–2968. 2010.PubMed/NCBI | |
Behrens G, Jochem C, Schmid D, Keimling M, Ricci C and Leitzmann MF: Physical activity and risk of pancreatic cancer: A systematic review and meta-analysis. Eur J Epidemiol. 30:279–298. 2015. View Article : Google Scholar : PubMed/NCBI | |
Melvin JC, Holmberg L, Rohrmann S, Loda M and Van Hemelrijck M: Serum lipid profiles and cancer risk in the context of obesity: Four meta-analyses. J Cancer Epidemiol. 2013:8238492013. View Article : Google Scholar : PubMed/NCBI | |
Strohmaier S, Edlinger M, Manjer J, Stocks T, Bjørge T, Borena W, Häggström C, Engeland A, Nagel G, Almquist M, et al: Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can). PLoS One. 8:e542422013. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Zhou T and Chen M: Meta analysis of the association of cholesterol with pancreatic carcinoma risk. J BUON. 20:109–113. 2014. View Article : Google Scholar | |
Chen H, Qin S, Wang M, Zhang T and Zhang S: Association between cholesterol intake and pancreatic cancer risk: Evidence from a meta-analysis. Sci Rep. 5:82432015. View Article : Google Scholar : PubMed/NCBI | |
Shen QW and Yao QY: Total fat consumption and pancreatic cancer risk: A meta-analysis of epidemiologic studies. Eur J Cancer Prev. 24:278–285. 2015. View Article : Google Scholar : PubMed/NCBI | |
Qin B, Xun P and He K: Fish or long-chain (n-3) PUFA intake is not associated with pancreatic cancer risk in a meta-analysis and systematic review. J Nutr. 142:1067–1073. 2012. View Article : Google Scholar : PubMed/NCBI | |
Ma YJ, Yu J, Xiao J and Cao BW: The consumption of omega-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: A systematic evaluation. Nutr Cancer. 67:112–118. 2015. View Article : Google Scholar : PubMed/NCBI | |
Bonovas S, Filioussi K and Sitaras NM: Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: Evidence from a meta-analysis of 12 studies. Am J Gastroenterol. 103:2646–2651. 2008. View Article : Google Scholar : PubMed/NCBI | |
Bradley MC, Hughes CM, Cantwell MM and Murray LJ: Statins and pancreatic cancer risk: A nested case-control study. Cancer Causes Control. 21:2093–2100. 2010. View Article : Google Scholar : PubMed/NCBI | |
Chiu HF, Chang CC, Ho SC, Wu TN and Yang CY: Statin use and the risk of pancreatic cancer: A population-based case-control study. Pancreas. 40:669–672. 2011. View Article : Google Scholar : PubMed/NCBI | |
Jacobs EJ, Newton CC, Thun MJ and Gapstur SM: Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res. 71:1763–1771. 2011. View Article : Google Scholar : PubMed/NCBI | |
Cui X, Xie Y, Chen M, Li J, Liao X, Shen J, Shi M, Li W, Zheng H and Jiang B: Statin use and risk of pancreatic cancer: A meta-analysis. Cancer Causes Control. 23:1099–1111. 2012. View Article : Google Scholar : PubMed/NCBI | |
Khurana V, Sheth A, Caldito G and Barkin JS: Statins reduce the risk of pancreatic cancer in humans: A case-control study of half a million veterans. Pancreas. 34:260–265. 2007. View Article : Google Scholar : PubMed/NCBI | |
Carey FJ, Little MW, Pugh TF, Ndokera R, Ing H, Clark A, Dennison A, Metcalfe MS, Robinson RJ and Hart AR: 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. 58:3308–3312. 2013. View Article : Google Scholar : PubMed/NCBI | |
Walker EJ, Ko AH, Holly EA and Bracci PM: Statin use and risk of pancreatic cancer: Results from a large, clinic-based case-control study. Cancer. 121:1287–1294. 2015. View Article : Google Scholar : PubMed/NCBI | |
Chagpar RB, Martin RC, Ahmad SA, Kim HJ, Rupp C, Weber S, Ebelhar A, Gilbert J, Brinkman A, Winslow E, et al: Medically managed hypercholesterolemia and insulin-dependent diabetes mellitus preoperatively predicts poor survival after surgery for pancreatic cancer. J Gastrointest Surg. 15:551–557. 2011. View Article : Google Scholar : PubMed/NCBI | |
Nakai Y, Isayama H, Sasaki T, Mizuno S, Sasahira N, Kogure H, Kawakubo K, Yamamoto N, Hirano K, Ijichi H, et al: Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with pancreatic cancer: Better prognosis with statin use in diabetic patients. Pancreas. 42:202–208. 2013. View Article : Google Scholar : PubMed/NCBI | |
Jeon CY, Pandol SJ and Goodman MT: Survival time in pancreatic cancer patients with metabolic syndrome varies by use of insulin and statins. Cancer Res. 74:(Suppl 19). 21732014. View Article : Google Scholar | |
Mikulski SM, Viera A, Darzynkiewicz Z and Shogen K: Synergism between a novel amphibian oocyte ribonuclease and lovastatin in inducing cytostatic and cytotoxic effects in human lung and pancreatic carcinoma cell lines. Br J Cancer. 66:304–310. 1992. View Article : Google Scholar : PubMed/NCBI | |
Sumi S, Beauchamp RD, Townsend CM Jr, Uchida T, Murakami M, Rajaraman S, Ishizuka J and Thompson JC: Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. Gastroenterology. 103:982–989. 1992. View Article : Google Scholar : PubMed/NCBI | |
Ura H, Obara T, Nishino N, Tanno S, Okamura K and Namiki M: Cytotoxicity of simvastatin to pancreatic adenocarcinoma cells containing mutant ras gene. Jpn J Cancer Res. 85:633–638. 1994. View Article : Google Scholar : PubMed/NCBI | |
Müller C, Bockhorn AG, Klusmeier S, Kiehl M, Roeder C, Kalthoff H and Koch OM: Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wild-type K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis. Int J Oncol. 12:717–723. 1998.PubMed/NCBI | |
Kamiński R, Kozar K, Kopeć M, Basak G, Skierski JS, Koronkiewicz M, Jakóbisiak M and Gołab J: Discussion on 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterology. 123:17472002. View Article : Google Scholar : PubMed/NCBI | |
Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y, Akedo H and Nakamura H: Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. Cancer Res. 61:4885–4891. 2001.PubMed/NCBI | |
Kusama T, Mukai M, Iwasaki T, Tatsuta M, Matsumoto Y, Akedo H, Inoue M and Nakamura H: 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Gastroenterology. 122:308–317. 2002. View Article : Google Scholar : PubMed/NCBI | |
Bocci G, Fioravanti A, Orlandi P, Bernardini N, Collecchi P, Del Tacca M and Danesi R: Fluvastatin synergistically enhances the antiproliferative effect of gemcitabine in human pancreatic cancer MIAPaCa-2 cells. Br J Cancer. 93:319–330. 2005. View Article : Google Scholar : PubMed/NCBI | |
Issat T, Nowis D, Legat M, Makowski M, Klejman MP, Urbanski J, Skierski J, Koronkiewicz M, Stoklosa T, Brzezinska A, et al: Potentiated antitumor effects of the combination treatment with statins and pamidronate in vitro and in vivo. Int J Oncol. 30:1413–1425. 2007.PubMed/NCBI | |
Liao J, Chung YT, Yang AL, Zhang M, Li H, Zhang W, Yan L and Yang GY: Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice. Mol Carcinog. 52:739–750. 2013. View Article : Google Scholar : PubMed/NCBI | |
Fendrich V, Sparn M, Lauth M, Knoop R, Plassmeier L, Bartsch DK and Waldmann J: Simvastatin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Pancreatology. 13:502–507. 2013. View Article : Google Scholar : PubMed/NCBI | |
Mohammed A, Qian L, Janakiram NB, Lightfoot S, Steele VE and Rao CV: Atorvastatin delays progression of pancreatic lesions to carcinoma by regulating PI3/AKT signaling in p48Cre/+ LSL-KrasG12D/+ mice. Int J Cancer. 131:1951–1962. 2012. View Article : Google Scholar : PubMed/NCBI | |
Mistafa O and Stenius U: Statins inhibit Akt/PKB signaling via P2X7 receptor in pancreatic cancer cells. Biochem Pharmacol. 78:1115–1126. 2009. View Article : Google Scholar : PubMed/NCBI | |
Ding N, Cui XX, Gao Z, Huang H, Wei X, Du Z, Lin Y, Shih WJ, Rabson AB, Conney AH, et al: A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors. Int J Oncol. 44:2139–2145. 2014.PubMed/NCBI | |
Gbelcová H, Svéda M, Laubertová L, Varga I, Vítek L, Kolář M, Strnad H, Zelenka J, Böhmer D and Ruml T: The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells. Lipids Health Dis. 12:1262013. View Article : Google Scholar : PubMed/NCBI | |
Ishikawa S, Nagai Y, Masuda T, Koga Y, Nakamura T, Imamura Y, Takamori H, Hirota M, Funakosi A, Fukushima M and Baba H: The role of oxysterol binding protein-related protein 5 in pancreatic cancer. Cancer Sci. 101:898–905. 2010. View Article : Google Scholar : PubMed/NCBI | |
Souchek JJ, Baine MJ, Lin C, Rachagani S, Gupta S, Kaur S, Lester K, Zheng D, Chen S, Smith L, et al: Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer. 111:1139–1149. 2014. View Article : Google Scholar : PubMed/NCBI | |
Maione F, Oliaro-Bosso S, Meda C, Di Nicolantonio F, Bussolino F, Balliano G, Viola F and Giraudo E: The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination. Sci Rep. 5:90542015. View Article : Google Scholar : PubMed/NCBI | |
Yang Y, Liu H, Li Z, Zhao Z, Yip-Schneider M, Fan Q, Schmidt CM, Chiorean EG, Xie J, Cheng L, et al: Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers. Int J Biochem Mol Biol. 2:89–98. 2011.PubMed/NCBI | |
Hussein D and Mo H: d-δ-Tocotrienol-mediated suppression of the proliferation of human PANC-1, MIA PaCa-2, and BxPC-3 pancreatic carcinoma cells. Pancreas. 38:e124–e136. 2009. View Article : Google Scholar : PubMed/NCBI | |
Shin-Kang S, Ramsauer VP, Lightner J, Chakraborty K, Stone W, Campbell S, Reddy SA and Krishnan K: Tocotrienols inhibit AKT and ERK activation and suppress pancreatic cancer cell proliferation by suppressing the ErbB2 pathway. Free Radic Biol Med. 51:1164–1174. 2011. View Article : Google Scholar : PubMed/NCBI | |
Guillaumond F, Bidaut G, Ouaissi M, Servais S, Gouirand V, Olivares O, Lac S, Borge L, Roques J, Gayet O, et al: Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci USA. 112:2473–2478. 2015. View Article : Google Scholar : PubMed/NCBI | |
Menter DG, Ramsauer VP, Harirforoosh S, Chakraborty K, Yang P, Hsi L, Newman RA and Krishnan K: Differential effects of pravastatin and simvastatin on the growth of tumor cells from different organ sites. PLoS One. 6:e288132011. View Article : Google Scholar : PubMed/NCBI | |
Gbelcová H, Lenícek M, Zelenka J, Knejzlík Z, Dvoráková G, Zadinová M, Poucková P, Kudla M, Balaz P, Ruml T and Vítek L: Differences in antitumor effects of various statins on human pancreatic cancer. Int J Cancer. 122:1214–1221. 2008. View Article : Google Scholar : PubMed/NCBI | |
Hong JY, Nam EM, Lee J, Park JO, Lee SC, Song SY, Choi SH, Heo JS, Park SH, Lim HY, et al: Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients. Cancer Chemother Pharmacol. 73:125–130. 2014. View Article : Google Scholar : PubMed/NCBI | |
Swierczynski J, Hebanowska A and Sledzinski T: Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer. World J Gastroenterol. 20:2279–2303. 2014. View Article : Google Scholar : PubMed/NCBI | |
Søreide K and Sund M: Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer. Cancer Lett. 356:281–288. 2015. View Article : Google Scholar : PubMed/NCBI |