Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Meta-Analysis

A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer

Author(s): Armin Khaghani, Karamali Kasiri, Saeid Heidari-Soureshjani, Catherine M.T. Sherwin and Hossein Mardani-Nafchi*

Volume 24, Issue 14, 2024

Published on: 29 May, 2024

Page: [1029 - 1037] Pages: 9

DOI: 10.2174/0118715206292712240522043350

Price: $65

Abstract

Background: Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer.

Objectives: This systematic review studied the association between statin intake and esophageal cancer.

Methods: To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05.

Results: Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113).

Conclusion: The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.

Keywords: Statin, esophageal cancer, systematic review, meta-analysis, statistical analyses, odds ratio.

Next »
Graphical Abstract
[1]
Deng, W.; Yu, R.; Yang, Z.; Dong, X.; Wang, W. Trends in conditional overall survival of esophageal cancer: A population-based study. Ann. Transl. Med., 2021, 9(2), 102.
[http://dx.doi.org/10.21037/atm-20-2798] [PMID: 33569404]
[2]
Hang, T.V.P.; Spiritos, Z.; Gamboa, A.M.; Chen, Z.; Force, S.; Patel, V.; Chawla, S.; Keilin, S.; Saba, N.F.; El-Rayes, B.; Cai, Q.; Willingham, F.F. Epidemiology of early esophageal adenocarcinoma. Clin. Endosc., 2022, 55(3), 372-380.
[http://dx.doi.org/10.5946/ce.2021.152] [PMID: 35144364]
[3]
Chen, Y.H.; Yu, H.C.; Lin, K.H.; Lin, H.S.; Hsu, P.I. Prevalence and risk factors for Barrett’s esophagus in Taiwan. World J. Gastroenterol., 2019, 25(25), 3231-3241.
[http://dx.doi.org/10.3748/wjg.v25.i25.3231] [PMID: 31333314]
[4]
Kambhampati, S.; Tieu, A.H.; Luber, B.; Wang, H.; Meltzer, S.J. Risk factors for progression of barrett’s esophagus to high grade dysplasia and esophageal adenocarcinoma. Sci. Rep., 2020, 10(1), 4899.
[http://dx.doi.org/10.1038/s41598-020-61874-7] [PMID: 32184470]
[5]
Beydoun, A.S.; Stabenau, K.A.; Altman, K.W.; Johnston, N. Cancer risk in barrett’s esophagus: A clinical review. Int. J. Mol. Sci., 2023, 24(7), 6018.
[http://dx.doi.org/10.3390/ijms24076018] [PMID: 37046992]
[6]
van den Brandt, P.A. The impact of a healthy lifestyle on the risk of esophageal and gastric cancer subtypes. Eur. J. Epidemiol., 2022, 37(9), 931-945.
[http://dx.doi.org/10.1007/s10654-022-00899-w] [PMID: 35982188]
[7]
Hussain, A.; Kaler, J.; Ray, S.D. The benefits outweigh the risks of treating hypercholesterolemia: The statin dilemma. Cureus, 2023, 15(1), e33648.
[http://dx.doi.org/10.7759/cureus.33648] [PMID: 36788860]
[8]
Su, C.H.; Islam, M.M.; Jia, G.; Wu, C.C. Statins and the risk of gastric cancer: A systematic review and meta-analysis. J. Clin. Med., 2022, 11(23), 7180.
[http://dx.doi.org/10.3390/jcm11237180] [PMID: 36498753]
[9]
Uemura, N.; Hayashi, H.; Baba, H. Statin as a therapeutic agent in gastroenterological cancer. World J. Gastrointest. Oncol., 2022, 14(1), 110-123.
[http://dx.doi.org/10.4251/wjgo.v14.i1.110] [PMID: 35116106]
[10]
Amin, F.; Fathi, F.; Reiner, Ž.; Banach, M.; Sahebkar, A. The role of statins in lung cancer. Arch. Med. Sci., 2021, 18(1), 141-152.
[http://dx.doi.org/10.5114/aoms/123225] [PMID: 35154535]
[11]
Barbalata, C.I.; Tefas, L.R.; Achim, M.; Tomuta, I.; Porfire, A.S. Statins in risk-reduction and treatment of cancer. World J. Clin. Oncol., 2020, 11(8), 573-588.
[http://dx.doi.org/10.5306/wjco.v11.i8.573] [PMID: 32879845]
[12]
Das, S.; Freedland, S.J. Statins and cancer prevention—association does not mean causation. Cancer Prev. Res., 2023, 16(1), 1-3.
[http://dx.doi.org/10.1158/1940-6207.CAPR-22-0420] [PMID: 36597731]
[13]
Peterson, J.; Welch, V.; Losos, M.; Tugwell, P. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses; Semantic Scholar, 2011, pp. 1-12.
[14]
Marelli, C.; Gunnarsson, C.; Ross, S.; Haas, S.; Stroup, D.F.; Cload, P.; Clopton, P.; DeMaria, A.N. Statins and risk of cancer: A retrospective cohort analysis of 45,857 matched pairs from an electronic medical records database of 11 million adult Americans. J. Am. Coll. Cardiol., 2011, 58(5), 530-537.
[http://dx.doi.org/10.1016/j.jacc.2011.04.015] [PMID: 21777752]
[15]
Pohl, H.; Wrobel, K.; Bojarski, C.; Voderholzer, W.; Sonnenberg, A.; Rösch, T.; Baumgart, D.C. Risk factors in the development of esophageal adenocarcinoma. Am. J. Gastroenterol., 2013, 108(2), 200-207.
[http://dx.doi.org/10.1038/ajg.2012.387] [PMID: 23247577]
[16]
Goldberg, A.; Gerkin, R.D.; Young, M. Medical prevention of barrett’s esophagus: Effects of statins, aspirin, non-aspirin NSAIDs, calcium, and multivitamins. Dig. Dis. Sci., 2015, 60(7), 2058-2062.
[http://dx.doi.org/10.1007/s10620-015-3569-0] [PMID: 25680872]
[17]
Alexandre, L.; Royston, C.; Caygill, C.; Bhattacharjee, S.; Dev, K.; Clark, A.; Watson, A.; Hart, A. PWE-130 Statin use and risk of malignant progression in patients with non-dysplastic barrett’s oesophagus: A nested case-control study. Gut, 2017, 66(Suppl. 2), A192.2-A193.
[http://dx.doi.org/10.1136/gutjnl-2017-314472.375]
[18]
Bhutta, H.Y.; Alexandre, L.; Clark, A.; Holt, S.; Lewis, M.; Hart, A. PWE-008 Do statins prevent the histological subtypes of oesophageal cancer? Prospective data from the UK general practice research database (GPRD). Gut, 2012, 61(Suppl. 2), A299.2-A300.
[http://dx.doi.org/ 10.1136/gutjnl-2012-302514d.8]
[19]
Altawil, J.; Irwin, B.; Jinjuvadia, R.; Antaki, F. Statins might not prevent progression to dysplasia and cancer in barrett’s esophagus. Off. J. Am. College Gastroenterol., 2011, 106, S32.
[20]
Iyer, P.G.; Borah, B.J.; Heien, H.; Chak, A. 705 rates and predictors of progression to adenocarcinoma in a large population based Barrett’s esophagus cohort. Gastroenterology, 2014, 146(5), S-121-S-122.
[http://dx.doi.org/10.1016/S0016-5085(14)60437-6]
[21]
Khurana, V.; Chalasani, R.; Caldito, G.; Fort, C. Statins reduce the incidence of lung cancer: a study of half a million US veterans. Eds. J. Clin. Oncol., 2005, 23(Suppl. 16), 1006.
[22]
Kaye, J.A.; Jick, H. Statin use and cancer risk in the General Practice Research Database. Br. J. Cancer, 2004, 90(3), 635-637.
[http://dx.doi.org/10.1038/sj.bjc.6601566] [PMID: 14760377]
[23]
Friedman, G.D.; Flick, E.D.; Udaltsova, N.; Chan Pharm, D. J.; Quesenberry, C.P., Jr; Habel, L.A. Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361 859 recipients. Pharmacoepidemiol. Drug Saf., 2008, 17(1), 27-36.
[http://dx.doi.org/10.1002/pds.1507] [PMID: 17944002]
[24]
Nguyen, D.M.; El-Serag, H.B.; Henderson, L.; Stein, D.; Bhattacharyya, A.; Sampliner, R.E. Medication usage and the risk of neoplasia in patients with Barrett’s esophagus. Clin. Gastroenterol. Hepatol., 2009, 7(12), 1299-1304.
[http://dx.doi.org/10.1016/j.cgh.2009.06.001] [PMID: 19523538]
[25]
Hippisley-Cox, J.; Coupland, C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ, 2010, 340(4), c2197.
[http://dx.doi.org/10.1136/bmj.c2197] [PMID: 20488911]
[26]
Nguyen, D.M.; Richardson, P.; El-Serag, H.B. Medications (NSAIDs, statins, proton pump inhibitors) and the risk of esophageal adenocarcinoma in patients with Barrett’s esophagus. Gastroenterology, 2010, 138(7), 2260-2266.
[http://dx.doi.org/10.1053/j.gastro.2010.02.045] [PMID: 20188100]
[27]
Kastelein, F.; Spaander, M.C.W.; Biermann, K.; Steyerberg, E.W.; Kuipers, E.J.; Bruno, M.J. Nonsteroidal anti-inflammatory drugs and statins have chemopreventative effects in patients with Barrett’s esophagus. Gastroenterology, 2011, 141(6), 2000-2008.
[http://dx.doi.org/10.1053/j.gastro.2011.08.036] [PMID: 21878200]
[28]
Vinogradova, Y.; Coupland, C.; Hippisley-Cox, J. Exposure to statins and risk of common cancers: A series of nested case-control studies. BMC Cancer, 2011, 11(1), 409.
[http://dx.doi.org/10.1186/1471-2407-11-409] [PMID: 21943022]
[29]
Beales, I.L.P.; Vardi, I.; Dearman, L. Regular statin and aspirin use in patients with Barrett’s oesophagus is associated with a reduced incidence of oesophageal adenocarcinoma. Eur. J. Gastroenterol. Hepatol., 2012, 24(8), 917-923.
[http://dx.doi.org/10.1097/MEG.0b013e3283543f01] [PMID: 22569083]
[30]
Kantor, E.D.; Onstad, L.; Blount, P.L.; Reid, B.J.; Vaughan, T.L. Use of statin medications and risk of esophageal adenocarcinoma in persons with Barrett’s esophagus. Cancer Epidemiol. Biomarkers Prev., 2012, 21(3), 456-461.
[http://dx.doi.org/10.1158/1055-9965.EPI-11-1014] [PMID: 22241250]
[31]
Lai, S.W.; Liao, K.F.; Lai, H.C.; Muo, C.H.; Sung, F.C. Atorvastatin correlates with decreased risk of esophageal cancer: A population-based case–control study from Taiwan. Libyan J. Med., 2012, 7(1), 18830.
[http://dx.doi.org/10.3402/ljm.v7i0.18830] [PMID: 22891079]
[32]
Beales, I.L.P.; Vardi, I.; Dearman, L.; Broughton, T. Statin use is associated with a reduction in the incidence of esophageal adenocarcinoma: A case control study. Dis. Esophagus, 2013, 26(8), 838-846.
[http://dx.doi.org/10.1111/j.1442-2050.2012.01412.x] [PMID: 22989236]
[33]
Chan, T.F.; Chiu, H.F.; Wu, C.H.; Lin, C.L.; Yang, C.Y. Statin use and the risk of esophageal cancer: A population-based case-control study. Expert Opin. Drug Saf., 2013, 12(3), 293-298.
[http://dx.doi.org/10.1517/14740338.2013.778241] [PMID: 23470154]
[34]
Agrawal, S.; Patel, P.; Agrawal, A.; Makhijani, N.; Markert, R.; Deidrich, W. Metformin use and the risk of esophageal cancer in Barrett esophagus. South. Med. J., 2014, 107(12), 774-779.
[http://dx.doi.org/10.14423/SMJ.0000000000000212] [PMID: 25502158]
[35]
Alexandre, L.; Clark, A.B.; Bhutta, H.Y.; Holt, S.; Lewis, M.P.N.; Hart, A.R. Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis. Gastroenterology, 2014, 146(3), 661-668.
[http://dx.doi.org/10.1053/j.gastro.2013.11.046] [PMID: 24315828]
[36]
Cooper, S.C.; Menon, S.; Nightingale, P.G.; Trudgill, N.J. Risk factors for the development of oesophageal adenocarcinoma in Barrett’s oesophagus: A UK primary care retrospective nested case–control study. United Eur. Gastroenterol. J., 2014, 2(2), 91-98.
[http://dx.doi.org/10.1177/2050640614523596] [PMID: 24918013]
[37]
Masclee, G.M.C.; Coloma, P.M.; Spaander, M.C.W.; Kuipers, E.J.; Sturkenboom, M.C.J.M. NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett’s oesophagus: A population-based case-control study. BMJ Open, 2015, 5(1), e006640.
[http://dx.doi.org/10.1136/bmjopen-2014-006640] [PMID: 25633286]
[38]
Nguyen, T.; Duan, Z.; Naik, A.D.; Kramer, J.R.; El-Serag, H.B. Statin use reduces risk of esophageal adenocarcinoma in US veterans with Barrett’s esophagus: A nested case-control study. Gastroenterology, 2015, 149(6), 1392-1398.
[http://dx.doi.org/10.1053/j.gastro.2015.07.009] [PMID: 26208896]
[39]
Krishnamoorthi, R.; Borah, B.; Heien, H.; Das, A.; Chak, A.; Iyer, P.G. Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett’s esophagus cohort. Gastrointest. Endosc., 2016, 84(1), 40-46.e7.
[http://dx.doi.org/10.1016/j.gie.2015.12.036] [PMID: 26772891]
[40]
Arai, J.; Niikura, R.; Hayakawa, Y.; Kawahara, T.; Honda, T.; Hasatani, K.; Yoshida, N.; Nishida, T.; Sumiyoshi, T.; Kiyotoki, S.; Ikeya, T.; Arai, M.; Suzuki, N.; Tsuji, Y.; Yamada, A.; Kawai, T.; Koike, K. Chemoprevention of oesophageal squamous-cell carcinoma and adenocarcinoma: A multicentre retrospective cohort study. Digestion, 2022, 103(3), 192-204.
[http://dx.doi.org/10.1159/000520924] [PMID: 34929693]
[41]
Kim, D.; Kim, H.J.; Ahn, H.S. Statins and the risk of gastric, colorectal, and esophageal cancer incidence and mortality: A cohort study based on data from the Korean national health insurance claims database. J. Cancer Res. Clin. Oncol., 2022, 148(10), 2855-2865.
[http://dx.doi.org/10.1007/s00432-022-04075-1] [PMID: 35660949]
[42]
Thomas, T.; Loke, Y.; Beales, I.L.P. Systematic review and meta-analysis: Use of statins is associated with a reduced incidence of oesophageal adenocarcinoma. J. Gastrointest. Cancer, 2018, 49(4), 442-454.
[http://dx.doi.org/10.1007/s12029-017-9983-0] [PMID: 28691139]
[43]
Singh, S.; Singh, A.G.; Singh, P.P.; Murad, M.H.; Iyer, P.G. Statins are associated with reduced risk of esophageal cancer, particularly in patients with Barrett’s esophagus: A systematic review and meta-analysis. Clin. Gastroenterol. Hepatol., 2013, 11(6), 620-629.
[http://dx.doi.org/10.1016/j.cgh.2012.12.036] [PMID: 23357487]
[44]
Beales, I.L.P.; Dearman, L.; Vardi, I.; Loke, Y. Reduced risk of barrett’s esophagus in statin users: Case–control study and meta-analysis. Dig. Dis. Sci., 2016, 61(1), 238-246.
[http://dx.doi.org/10.1007/s10620-015-3869-4] [PMID: 26386857]
[45]
Deng, H.Y.; Lan, X.; Zheng, X.; Zha, P.; Zhou, J.; Wang, R.L.; Jiang, R.; Qiu, X.M. The association between statin use and survival of esophageal cancer patients. Medicine (Baltimore), 2019, 98(29), e16480.
[http://dx.doi.org/10.1097/MD.0000000000016480] [PMID: 31335710]
[46]
Lv, J.; Chen, P.; Wu, J.; Wen, Z.; Zhao, C. The association between statin use and prognosis in esophageal cancer patients: A meta-analysis. Medicine (Baltimore), 2023, 102(12), e33359.
[http://dx.doi.org/10.1097/MD.0000000000033359] [PMID: 36961185]
[47]
Wijarnpreecha, K.; Panjawatanan, P.; Leelasinjaroen, L.; Ungprasert, P. Statins and gastroesophageal reflux disease. J. Postgrad. Med., 2019, 65(4), 207-211.
[http://dx.doi.org/10.4103/jpgm.JPGM_271_18] [PMID: 31603078]
[48]
Lin, C.J.; Liao, W.C.; Chen, Y.A.; Lin, H.J.; Feng, C.L.; Lin, C.L.; Lin, Y.J.; Kao, M.C.; Huang, M.Z.; Lai, C.H.; Kao, C.H. Statin therapy is associated with reduced risk of peptic ulcer disease in the taiwanese population. Front. Pharmacol., 2017, 8, 210.
[http://dx.doi.org/10.3389/fphar.2017.00210] [PMID: 28503146]
[49]
Singh, P.P.; Singh, S. Statins are associated with reduced risk of gastric cancer: a systematic review and meta-analysis. Ann. Oncol., 2013, 24(7), 1721-1730.
[http://dx.doi.org/10.1093/annonc/mdt150] [PMID: 23599253]
[50]
Chang, Y.; Liu, Q.; Zhou, Z.; Ding, Y.; Yang, M.; Xu, W.; Chen, K.; Zhang, Q.; Wang, Z.; Li, H. Can statin treatment reduce the risk of hepatocellular carcinoma? A systematic review and meta-analysis. Technol. Cancer Res. Treat., 2020, 19.
[http://dx.doi.org/10.1177/1533033820934881] [PMID: 32552476]
[51]
Fatehi, H. A.; Wong, J.V.S. Statins as Potential Therapeutics for Esophageal Cancer. J. Gastrointest. Cancer, 2021, 52(3), 833-838.
[http://dx.doi.org/10.1007/s12029-021-00648-4] [PMID: 34056697]
[52]
Shah, S.C.; Glass, J.; Giustino, G.; Hove, J.R.; Castaneda, D.; Torres, J.; Kumar, A.; Elman, J.; Ullman, T.A.; Itzkowitz, S.H. Statin exposure is not associated with reduced prevalence of colorectal neoplasia in patients with inflammatory bowel disease. Gut Liver, 2019, 13(1), 54-61.
[http://dx.doi.org/10.5009/gnl18178] [PMID: 30400722]
[53]
Stryjkowska-Góra, A.; Karczmarek-Borowska, B.; Góra, T.; Krawczak, K. Statins and cancers. Contemp. Oncol. (Pozn.), 2015, 3(3), 167-175.
[http://dx.doi.org/10.5114/wo.2014.44294] [PMID: 26557755]
[54]
Borgquist, S.; Bjarnadottir, O.; Kimbung, S.; Ahern, T.P. Statins: a role in breast cancer therapy? J. Intern. Med., 2018, 284(4), 346-357.
[http://dx.doi.org/10.1111/joim.12806] [PMID: 29923256]
[55]
Bruder-Nascimento, T.; Callera, G.E.; Montezano, A.C.; Belin de Chantemele, E.J.; Tostes, R.C.; Touyz, R.M. Atorvastatin inhibits pro-inflammatory actions of aldosterone in vascular smooth muscle cells by reducing oxidative stress. Life Sci., 2019, 221, 29-34.
[http://dx.doi.org/10.1016/j.lfs.2019.01.043] [PMID: 30721707]
[56]
Lin, T.Y.; Lan, W.H.; Chiu, Y.F.; Feng, C.L.; Chiu, C.H.; Kuo, C.J.; Lai, C.H. Statins’ regulation of the virulence factors of Helicobacter pylori and the production of ROS may inhibit the development of gastric cancer. Antioxidants, 2021, 10(8), 1293.
[http://dx.doi.org/10.3390/antiox10081293] [PMID: 34439541]
[57]
Grabarek, B.O. Boroń, D.; Morawiec, E.; Michalski, P.; Palazzo-Michalska, V.; Pach, Ł.; Dziuk, B.; Ś;wider, M.; Zmarzły, N. Crosstalk between statins and cancer prevention and therapy: An update. Pharmaceuticals (Basel), 2021, 14(12), 1220.
[http://dx.doi.org/10.3390/ph14121220] [PMID: 34959621]
[58]
Di Bello, E.; Zwergel, C.; Mai, A.; Valente, S. The innovative potential of statins in cancer: New targets for new therapies. Front Chem., 2020, 8, 516.
[http://dx.doi.org/10.3389/fchem.2020.00516] [PMID: 32626692]

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