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Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

Statins and the risk of gastric cancer in diabetes patients

Authors: Jeeyun Lee, Soo Hyeon Lee, Kyu Yeon Hur, Sook Young Woo, Sun Woo Kim, Won Ki Kang

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

Several studies have suggested a cancer risk reduction in statin users although the evidence remains weak for stomach cancer. The purpose of this study was to use an exact-matching case–control design to examine the risk of gastric cancer associated with the use of statins in a cohort of patients with diabetes.

Methods

Cases were defined as patients with incident gastric cancer identified by International Classification of Diseases 16.0 ~ 16.9 recorded at Samsung Medical Center database during the period of 1999 to 2008, at least 6 months after the entry date of diabetes code. Each gastric cancer case patient was matched with one control patient from the diabetes patient registry in a 1:1 fashion, blinded to patient outcomes.

Results

A total of 983 cases with gastric cancer and 983 controls without gastric cancer, matched by age and sex, were included in the analysis. The presence of prescription for any statin was inversely associated with gastric cancer risk in the unadjusted conditional logistic regression model (OR: 0.18; 95% CI: 0.14 – 0.24; P < .0001). Multivariate analysis using conditional logistic regression with Bonferroni’s correction against aspirin indicated a significant reduction in the risk of gastric cancer in diabetes patients with statin prescriptions (OR: 0.21; 95% CI: 0.16 – 0.28; P < .0001). After adjustment for aspirin use, a longer duration of statin use was associated with reduced risk of gastric cancer, with statistical significance (P<.0001).

Conclusions

A strong inverse association was found between the risk of gastric adenocarcinoma and statin use in diabetic patients.
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Literature
1.
go back to reference Goldstein JL, Brown MS: Regulation of the mevalonate pathway. Nature. 1990, 343 (6257): 425-430. 10.1038/343425a0.CrossRefPubMed Goldstein JL, Brown MS: Regulation of the mevalonate pathway. Nature. 1990, 343 (6257): 425-430. 10.1038/343425a0.CrossRefPubMed
2.
go back to reference Casey PJ: Protein lipidation in cell signaling. Science (New York, NY. 1995, 268 (5208): 221-225. 10.1126/science.7716512.CrossRef Casey PJ: Protein lipidation in cell signaling. Science (New York, NY. 1995, 268 (5208): 221-225. 10.1126/science.7716512.CrossRef
3.
go back to reference Rando RR: Chemical biology of isoprenylation/methylation. Biochem Soc Trans. 1996, 24 (3): 682-687.CrossRefPubMed Rando RR: Chemical biology of isoprenylation/methylation. Biochem Soc Trans. 1996, 24 (3): 682-687.CrossRefPubMed
4.
go back to reference Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G: Statins and the risk of colorectal cancer. N Engl J Med. 2005, 352 (21): 2184-2192. 10.1056/NEJMoa043792.CrossRefPubMed Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G: Statins and the risk of colorectal cancer. N Engl J Med. 2005, 352 (21): 2184-2192. 10.1056/NEJMoa043792.CrossRefPubMed
5.
go back to reference 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: c2197-10.1136/bmj.c2197.CrossRefPubMedPubMedCentral 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: c2197-10.1136/bmj.c2197.CrossRefPubMedPubMedCentral
6.
go back to reference Yang X, So WY, Ma RC, Ko GT, Kong AP, Zhao H, Luk AO, Lam CW, Ho CS, Tong PC, et al: Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry. Diabetes Care. 2009, 32 (10): 1826-1832. 10.2337/dc09-0725.CrossRefPubMedPubMedCentral Yang X, So WY, Ma RC, Ko GT, Kong AP, Zhao H, Luk AO, Lam CW, Ho CS, Tong PC, et al: Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry. Diabetes Care. 2009, 32 (10): 1826-1832. 10.2337/dc09-0725.CrossRefPubMedPubMedCentral
7.
go back to reference Yang X, Zhao H, Sui Y, Ma RC, So WY, Ko GT, Kong AP, Ozaki R, Yeung CY, Xu G, et al: Additive interaction between the renin-angiotensin system and lipid metabolism for cancer in type 2 diabetes. Diabetes. 2009, 58 (7): 1518-1525. 10.2337/db09-0105.CrossRefPubMedPubMedCentral Yang X, Zhao H, Sui Y, Ma RC, So WY, Ko GT, Kong AP, Ozaki R, Yeung CY, Xu G, et al: Additive interaction between the renin-angiotensin system and lipid metabolism for cancer in type 2 diabetes. Diabetes. 2009, 58 (7): 1518-1525. 10.2337/db09-0105.CrossRefPubMedPubMedCentral
8.
go back to reference El-Serag HB, Johnson ML, Hachem C, Morgana RO: Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009, 136 (5): 1601-1608. 10.1053/j.gastro.2009.01.053.CrossRefPubMedPubMedCentral El-Serag HB, Johnson ML, Hachem C, Morgana RO: Statins are associated with a reduced risk of hepatocellular carcinoma in a large cohort of patients with diabetes. Gastroenterology. 2009, 136 (5): 1601-1608. 10.1053/j.gastro.2009.01.053.CrossRefPubMedPubMedCentral
9.
go back to reference Kuoppala J, Lamminpaa A, Pukkala E: Statins and cancer: A systematic review and meta-analysis. Eur J Cancer. 2008, 44 (15): 2122-2132. 10.1016/j.ejca.2008.06.025.CrossRefPubMed Kuoppala J, Lamminpaa A, Pukkala E: Statins and cancer: A systematic review and meta-analysis. Eur J Cancer. 2008, 44 (15): 2122-2132. 10.1016/j.ejca.2008.06.025.CrossRefPubMed
10.
go back to reference 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: 409-10.1186/1471-2407-11-409.CrossRefPubMedPubMedCentral 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: 409-10.1186/1471-2407-11-409.CrossRefPubMedPubMedCentral
11.
go back to reference Hachem C, Morgan R, Johnson M, Kuebeler M, El-Serag H: Statins and the risk of colorectal carcinoma: a nested case–control study in veterans with diabetes. Am J Gastroenterol. 2009, 104 (5): 1241-1248. 10.1038/ajg.2009.64.CrossRefPubMedPubMedCentral Hachem C, Morgan R, Johnson M, Kuebeler M, El-Serag H: Statins and the risk of colorectal carcinoma: a nested case–control study in veterans with diabetes. Am J Gastroenterol. 2009, 104 (5): 1241-1248. 10.1038/ajg.2009.64.CrossRefPubMedPubMedCentral
12.
go back to reference Landgren O, Zhang Y, Zahm SH, Inskip P, Zheng T, Baris D: Risk of multiple myeloma following medication use and medical conditions: a case–control study in Connecticut women. Cancer Epidemiol Biomarkers Prev. 2006, 15 (12): 2342-2347. 10.1158/1055-9965.EPI-06-0097.CrossRefPubMed Landgren O, Zhang Y, Zahm SH, Inskip P, Zheng T, Baris D: Risk of multiple myeloma following medication use and medical conditions: a case–control study in Connecticut women. Cancer Epidemiol Biomarkers Prev. 2006, 15 (12): 2342-2347. 10.1158/1055-9965.EPI-06-0097.CrossRefPubMed
13.
go back to reference Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR: The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case–control study. Cancer. 2004, 100 (11): 2308-2316. 10.1002/cncr.20271.CrossRefPubMed Boudreau DM, Gardner JS, Malone KE, Heckbert SR, Blough DK, Daling JR: The association between 3-hydroxy-3-methylglutaryl conenzyme A inhibitor use and breast carcinoma risk among postmenopausal women: a case–control study. Cancer. 2004, 100 (11): 2308-2316. 10.1002/cncr.20271.CrossRefPubMed
14.
go back to reference Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE: Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med. 2005, 165 (19): 2264-2271. 10.1001/archinte.165.19.2264.CrossRefPubMed Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE: Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med. 2005, 165 (19): 2264-2271. 10.1001/archinte.165.19.2264.CrossRefPubMed
15.
go back to reference Nowakowski GS, Maurer MJ, Habermann TM, Ansell SM, Macon WR, Ristow KM, Allmer C, Slager SL, Witzig TE, Cerhan JR: Statin use and prognosis in patients with diffuse large B-cell lymphoma and follicular lymphoma in the rituximab era. J Clin Oncol. 2010, 28 (3): 412-417. 10.1200/JCO.2009.23.4245.CrossRefPubMed Nowakowski GS, Maurer MJ, Habermann TM, Ansell SM, Macon WR, Ristow KM, Allmer C, Slager SL, Witzig TE, Cerhan JR: Statin use and prognosis in patients with diffuse large B-cell lymphoma and follicular lymphoma in the rituximab era. J Clin Oncol. 2010, 28 (3): 412-417. 10.1200/JCO.2009.23.4245.CrossRefPubMed
16.
go back to reference Lee J, Lee I, Park C, Kang WK: Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells. Biochem Biophys Res Commun. 2006, 339 (3): 748-754. 10.1016/j.bbrc.2005.11.075.CrossRefPubMed Lee J, Lee I, Park C, Kang WK: Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells. Biochem Biophys Res Commun. 2006, 339 (3): 748-754. 10.1016/j.bbrc.2005.11.075.CrossRefPubMed
17.
go back to reference Lee J, Jung KH, Park YS, Ahn JB, Shin SJ, Im SA, Shin DB, Kim TW, Lee N, Oh Do Y, et al: Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study. Cancer Chemother Pharmacol. 2009, 64 (4): 657-663. 10.1007/s00280-008-0913-5.CrossRefPubMed Lee J, Jung KH, Park YS, Ahn JB, Shin SJ, Im SA, Shin DB, Kim TW, Lee N, Oh Do Y, et al: Simvastatin plus irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) as first-line chemotherapy in metastatic colorectal patients: a multicenter phase II study. Cancer Chemother Pharmacol. 2009, 64 (4): 657-663. 10.1007/s00280-008-0913-5.CrossRefPubMed
18.
go back to reference Lee J, Lee I, Han B, Park JO, Jang J, Park C, Kang WK: Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations. J Natl Cancer Inst. 2011, 103 (8): 674-688. 10.1093/jnci/djr070.CrossRefPubMed Lee J, Lee I, Han B, Park JO, Jang J, Park C, Kang WK: Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations. J Natl Cancer Inst. 2011, 103 (8): 674-688. 10.1093/jnci/djr070.CrossRefPubMed
19.
go back to reference Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008, 8 (12): 915-928. 10.1038/nrc2536.CrossRefPubMed Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008, 8 (12): 915-928. 10.1038/nrc2536.CrossRefPubMed
20.
go back to reference Carlberg M, Dricu A, Blegen H, Wang M, Hjertman M, Zickert P, Hoog A, Larsson O: Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth. J Biol Chem. 1996, 271 (29): 17453-17462. 10.1074/jbc.271.29.17453.CrossRefPubMed Carlberg M, Dricu A, Blegen H, Wang M, Hjertman M, Zickert P, Hoog A, Larsson O: Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth. J Biol Chem. 1996, 271 (29): 17453-17462. 10.1074/jbc.271.29.17453.CrossRefPubMed
21.
go back to reference Girnita L, Wang M, Xie Y, Nilsson G, Dricu A, Wejde J, Larsson O: Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications. Anticancer Drug Des. 2000, 15 (1): 67-72.PubMed Girnita L, Wang M, Xie Y, Nilsson G, Dricu A, Wejde J, Larsson O: Inhibition of N-linked glycosylation down-regulates insulin-like growth factor-1 receptor at the cell surface and kills Ewing's sarcoma cells: therapeutic implications. Anticancer Drug Des. 2000, 15 (1): 67-72.PubMed
22.
go back to reference Sekine Y, Furuya Y, Nishii M, Koike H, Matsui H, Suzuki K: Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor. Biochem Biophys Res Commun. 2008, 372 (2): 356-361. 10.1016/j.bbrc.2008.05.043.CrossRefPubMed Sekine Y, Furuya Y, Nishii M, Koike H, Matsui H, Suzuki K: Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor. Biochem Biophys Res Commun. 2008, 372 (2): 356-361. 10.1016/j.bbrc.2008.05.043.CrossRefPubMed
23.
go back to reference Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adam HO: A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12 (1): 13-21. 10.1023/A:1008995217664.CrossRefPubMed Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adam HO: A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12 (1): 13-21. 10.1023/A:1008995217664.CrossRefPubMed
24.
go back to reference Larsson SWA: Epidemiology of obesity and diabetes: prevalence and trends Obesity and Diabetes. 2006, Boston: Humana PressCrossRef Larsson SWA: Epidemiology of obesity and diabetes: prevalence and trends Obesity and Diabetes. 2006, Boston: Humana PressCrossRef
25.
go back to reference Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H: Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11 (2 Pt 1): 466-472.PubMed Ishikawa M, Kitayama J, Kazama S, Hiramatsu T, Hatano K, Nagawa H: Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11 (2 Pt 1): 466-472.PubMed
26.
go back to reference Strasak AM, Pfeiffer RM, Brant LJ, Rapp K, Hilbe W, Oberaigner W, Lang S, Borena W, Concin H, Diem G, et al: Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol. 2009, 20 (6): 1113-1120. 10.1093/annonc/mdn736.CrossRefPubMedPubMedCentral Strasak AM, Pfeiffer RM, Brant LJ, Rapp K, Hilbe W, Oberaigner W, Lang S, Borena W, Concin H, Diem G, et al: Time-dependent association of total serum cholesterol and cancer incidence in a cohort of 172,210 men and women: a prospective 19-year follow-up study. Ann Oncol. 2009, 20 (6): 1113-1120. 10.1093/annonc/mdn736.CrossRefPubMedPubMedCentral
27.
go back to reference Sherwin RW, Wentworth DN, Cutler JA, Hulley SB, Kuller LH, Stamler J: Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial. JAMA. 1987, 257 (7): 943-948. 10.1001/jama.1987.03390070063024.CrossRefPubMed Sherwin RW, Wentworth DN, Cutler JA, Hulley SB, Kuller LH, Stamler J: Serum cholesterol levels and cancer mortality in 361,662 men screened for the Multiple Risk Factor Intervention Trial. JAMA. 1987, 257 (7): 943-948. 10.1001/jama.1987.03390070063024.CrossRefPubMed
28.
go back to reference Neaton JD, Blackburn H, Jacobs D, Kuller L, Lee DJ, Sherwin R, Shih J, Stamler J, Wentworth D: Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992, 152 (7): 1490-1500. 10.1001/archinte.1992.00400190110021.CrossRefPubMed Neaton JD, Blackburn H, Jacobs D, Kuller L, Lee DJ, Sherwin R, Shih J, Stamler J, Wentworth D: Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992, 152 (7): 1490-1500. 10.1001/archinte.1992.00400190110021.CrossRefPubMed
29.
go back to reference Benn M, Tybjaerg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG: Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study. J Natl Cancer Inst. 2011, 103 (6): 508-519. 10.1093/jnci/djr008.CrossRefPubMed Benn M, Tybjaerg-Hansen A, Stender S, Frikke-Schmidt R, Nordestgaard BG: Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study. J Natl Cancer Inst. 2011, 103 (6): 508-519. 10.1093/jnci/djr008.CrossRefPubMed
30.
go back to reference Yang XL, Ma RC, So WY, Kong AP, Xu G, Chan JC: Addressing different biases in analysing drug use on cancer risk in diabetes in non-clinical trial settings–what, why and how?. Diabetes Obes Metab. 2012, 14 (7): 579-585. 10.1111/j.1463-1326.2011.01551.x.CrossRefPubMed Yang XL, Ma RC, So WY, Kong AP, Xu G, Chan JC: Addressing different biases in analysing drug use on cancer risk in diabetes in non-clinical trial settings–what, why and how?. Diabetes Obes Metab. 2012, 14 (7): 579-585. 10.1111/j.1463-1326.2011.01551.x.CrossRefPubMed
Metadata
Title
Statins and the risk of gastric cancer in diabetes patients
Authors
Jeeyun Lee
Soo Hyeon Lee
Kyu Yeon Hur
Sook Young Woo
Sun Woo Kim
Won Ki Kang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-596

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