To evaluate whether statin use influences gastrointestinal cancer prognosis in patients with diabetes mellitus (DM).
Methods:
We reviewed all DM patients diagnosed at Roswell Park Cancer Institute with emergent gastrointestinal malignancy (January 2003 to December 2010) (N = 222). Baseline demographic, clinical history, and cancer outcomes were documented. Overall survival (OS) and disease-free survival (DFS) comparisons across various treatment groups were assessed by Kaplan-Meier and Cox proportional hazards.
Results:
Use of statin, alone or in combination, was associated with improved OS and DFS (hazard ratio [HR] = 0.65, P = .06; HR = 0.60, P < .02). We report similar OS and DFS advantage among users of mono- or combined metformin therapy (HR = 0.55, P < .01; HR = 0.63, P < .02). Concomitant use of metformin and statin provided a synergistic OS and DFS benefit (HR = 0.42, P < .01; HR = 0.44, P < .01). Despite significant tobacco and alcohol use history, patients with upper gastrointestinal cancers derived enhanced cancer outcomes from this combination (HR = 0.34, P < .01; HR = 0.43, P < .02), while receiving a statin without metformin or metformin without a statin did not provide significant cancer-related benefits.
Conclusion:
Use of statin and metformin provides a synergistic improvement in gastrointestinal malignancies outcomes.
TorreLABrayFSiegelRL. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.
2.
YoonJMSonKYEomCS. Pre-existing diabetes mellitus increases the risk of gastric cancer: a meta-analysis. World J Gastroenterol. 2013;19(6):936–945.
3.
TsengCHTsengFH. Diabetes and gastric cancer: the potential links. World J Gastroenterol. 2014;20(7):1701–1711.
4.
ValentF. Diabetes mellitus and cancer of the digestive organs: an Italian population based cohort study. J Diabetes Complications. 2015;29(8):1056–1061.
5.
ZandersMMvan Herk-SukelMPVissersPA. Are metformin, statin and aspirin use still associated with overall mortality among colorectal cancer patients with diabetes if adjusted for one another?Br J Cancer. 2015;113(3):403–410.
6.
LeeCKJungMJungI. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg. 2016;263(1):96–102.
7.
KimYIKimSYChoSJ. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. Aliment Pharmacol Ther. 2014;39(8):854–863.
8.
TsengCH. Diabetes, metformin use, and colon cancer: a population-based cohort study in Taiwan. Eur J Endocrinol. 2012;167(3):409–416.
9.
TsengCH. Diabetes, insulin use and Helicobacter pylori eradication: a retrospective cohort study. BMC Gastroenterol. 2012;12:46.
10.
KamangarFQiaoYLBlaserMJ. Helicobacter pylori and oesophageal and gastric cancers in a prospective study in China. Br J Cancer. 2007;96(1):172–176.
11.
DevrajaniBRShahSZSoomroAA. Type 2 diabetes mellitus: a risk factor for Helicobacter pylori infection: a hospital based case-control study. Int J Diabetes Dev Ctries. 2010;30(1):22–26.
12.
BenerAMicallefRAfifiM. Association between type 2 diabetes mellitus and Helicobacter pylori infection. Turk J Gastroenterol. 2007;18(4):225–229.
13.
ChenYBlaserMJ. Association between gastric Helicobacter pylori colonization and glycated hemoglobin levels. J Infect Dis. 2012;205(8):1195–1202.
14.
HuangYSunJWangX. Helicobacter pylori infection decreases metformin tolerance in patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2015;17(2):128–133.
15.
EvansJMDonnellyLAEmslie-SmithAM. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330(7503):1304–1305.
16.
DowlingRJNiraulaSStambolicV. Metformin in cancer: translational challenges. J Mol Endocrinol. 2012;48(3):r31–r43.
17.
CeacareanuAC. A pharmacist’s perspective on metformin use and cancer outcomes. J Pharm Pract. 2015;28(1):44–45.
18.
WintrobZA. Should pharmacokinetic safety challenges prevent metformin use in patients with cancer?J Pharm Pract. 2015;28(1):48–49.
19.
Mc MenaminUCMurrayLJHughesCM. Metformin use and survival after colorectal cancer: a population-based cohort study. Int J Cancer. 2016;138(1): 369–379.
20.
MarksARPietrofesaRAJensenCD. Metformin use and risk of colorectal adenoma after polypectomy in patients with type 2 diabetes mellitus. Cancer Epidemiol Biomarkers Prev. 2015;24(11):1692–1698.
21.
BaeSWongHLTieJ. Impact of diabetes status and medication on presentation, treatment, and outcome of stage ii colon cancer patients. J Cancer Epidemiol. 2015;2015:189132.
22.
KimYHNohRChoSY. Inhibitory effect of metformin therapy on the incidence of colorectal advanced adenomas in patients with diabetes. Intest Res. 2015;13(2):145–152.
23.
SpieringsLELagardeSMvan OijenMG. Metformin use during treatment of potentially curable esophageal cancer patients is not associated with better outcomes. Ann Surg Oncol. 2015;22(suppl 3):766–771.
24.
Van De VoordeLJanssenLLarueR. Can metformin improve ‘the tomorrow’ of patients treated for oesophageal cancer?Eur J Surg Oncol. 2015;41(10):1333–1339.
25.
BeckerCMeierCRJickSS. Case-control analysis on metformin and cancer of the esophagus. Cancer Causes Control. 2013;24(10):1763–1770.
26.
GreenhillC.Gastric cancer. Metformin improves survival and recurrence rate in patients with diabetes and gastric cancer. Nat Rev Gastroenterol Hepatol. 2015;12(3):124.
27.
LiuYTangWWangJ. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control. 2014;25(2):237–249.
28.
MaZWangWJinG. Effect of statins on gastric cancer incidence: a meta-analysis of case control studies. J Cancer Res Ther. 2014;10(4):859–865.
29.
ThriftAP. Esophageal adenocarcinoma: the influence of medications used to treat comorbidities on cancer prognosis. Clin Gastroenterol Hepatol. 2015;13(13):2225–2232.
30.
NguyenTDuanZNaikAD. 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.
31.
NseirWKhateebJTatourI. Long-term statin therapy affects the severity of chronic gastritis. Helicobacter. 2010;15(6):510–515.
FreedmanNDDerakhshanMHAbnetCC. Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women. Eur J Cancer. 2010;46(13):2473–2478.
34.
HowladerNMariottoABWoloshinS. Providing clinicians and patients with actual prognosis: cancer in the context of competing causes of death. J Natl Cancer Inst Monogr. 2014;2014(49):255–264.
