Diabetes Mellitus and Incidence and Mortality of Gastric Cancer: A Meta-Analysis

Abstract

Aims:

Epidemiologic studies have examined the possible associations between diabetes mellitus (DM) and gastric cancer (GC), but the results are inconclusive. We conducted a meta-analysis to assess the evidence regarding the associations between diabetes and incidences of, or mortality from, gastric cancer.

Methods:

PubMed, Embase and Web of Science were searched up to Oct 20, 2011. We identified studies that included effects estimates with 95% confidence intervals (CIs) of the associations between GC and diabetes. Summary RRs for the GC incidence and mortality were calculated using random-effects model; subgroup analyses were also performed. Heterogeneity among studies was examined using Q and I² statistics.

Results:

A total of 7 case-control and 18 cohort studies met the inclusion criteria. The summary RR showed a slightly statistical link between history of DM and GC incidence (RR=1.11, 95% CI: 1.00–1.24, p=0.045, I²=79.5%). In the subgroup analyses, a positive association was noted among the studies conducted in Asia (summary RR=1.19, 95% CI: 1.07–1.32, I²=29.8%). Additionally, slight associations between DM and GC were observed by pooling the data of type 2 DM, cohort studies and the studies controlling more confounders, respectively. Furthermore, mortality from GC with diabetes was increased compared with individuals without diabetes (summary RR=1.29, 95% CI: 1.04–1.59). No publication bias was found.

Conclusion:

Individuals with diabetes have an increased risk of developing gastric cancer, and are positively associated with gastric cancer mortality. Large better-designed cohort studies are needed to verify this conclusion.

Key words

diabetes mellitus - gastric neoplasm - epidemiology - meta-analysis

* 

^* The first 2 authors contributed equally to this work.

• References

• 1 Jemal A, Bray F, Center MM et al. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90
• 2 Obst B, Wagner S, Sewing KF et al. Helicobacter pylori causes DNA damage in gastric epithelial cells. Carcinogenesis 2000; 21: 1111-1115
• 3 Vigneri P, Frasca F, Sciacca L et al. Diabetes and cancer. Endocr Relat Cancer 2009; 16: 1103-1123
• 4 Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92: 2076-2083
• 5 Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005; 97: 1679-1687
• 6 El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006; 4: 369-380
• 7 Friberg E, Orsini N, Mantzoros CS et al. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007; 50: 1365-1374
• 8 Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007; 121: 856-862
• 9 Larsson SC, Wolk A. Diabetes mellitus and incidence of kidney cancer: a meta-analysis of cohort studies. Diabetologia. 2011
• 10 Chao C, Page JH. Type 2 diabetes mellitus and risk of non-Hodgkin lymphoma: a systematic review and meta-analysis. Am J Epidemiol 2008; 168: 471-480
• 11 Bonovas S, Filioussi K, Tsantes A. Diabetes mellitus and risk of prostate cancer: a meta-analysis. Diabetologia 2004; 47: 1071-1078
• 12 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177-188
• 13 Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539-1558
• 14 Higgins JP, Thompson SG, Deeks JJ et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560
• 15 Egger M, Davey Smith G, Schneider M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629-634
• 16 O’Mara BA, Byers T, Schoenfeld E. Diabetes mellitus and cancer risk: a multisite case-control study. J Chronic Dis 1985; 38: 435-441
• 17 Lin SW, Freedman ND, Hollenbeck A et al. Prospective study of self-reported diabetes and risk of upper gastrointestinal cancers. Cancer Epidemiol Biomarkers Prev. 2011
• 18 Atchison EA, Gridley G, Carreon JD et al. Risk of cancer in a large cohort of U.S. veterans with diabetes. Int J Cancer 2011; 128: 635-643
• 19 Hemminki K, Li X, Sundquist J et al. Risk of cancer following hospitalization for type 2 diabetes. Oncologist 2010; 15: 548-555
• 20 Ogunleye AA, Ogston SA, Morris AD et al. A cohort study of the risk of cancer associated with type 2 diabetes. Br J Cancer 2009; 101: 1199-1201
• 21 Kuriki K, Hirose K, Tajima K. Diabetes and cancer risk for all and specific sites among Japanese men and women. Eur J Cancer Prev 2007; 16: 83-89
• 22 Rousseau MC, Parent ME, Pollak MN et al. Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal, Canada. Int J Cancer 2006; 118: 2105-2109
• 23 Khan M, Mori M, Fujino Y et al. Japan Collaborative Cohort Study G. Site-specific cancer risk due to diabetes mellitus history: evidence from the Japan Collaborative Cohort (JACC) Study. Asian Pac J Cancer Prev 2006; 7: 253-259
• 24 Jun JK, Gwack J, Park SK et al. Fasting serum glucose level and gastric cancer risk in a nested case-control study. J Prev Med Public Health 2006; 39: 493-498
• 25 Inoue M, Iwasaki M, Otani T et al. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 2006; 166: 1871-1877
• 26 Swerdlow AJ, Laing SP, Qiao Z et al. Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer 2005; 92: 2070-2075
• 27 Rubenstein JH, Davis J, Marrero JA et al. Relationship between diabetes mellitus and adenocarcinoma of the oesophagus and gastric cardia. Aliment Pharmacol Ther 2005; 22: 267-271
• 28 Jee SH, Ohrr H, Sull JW et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA 2005; 293: 194-202
• 29 Koppert LB, Janssen-Heijnen ML, Louwman MW et al. Comparison of comorbidity prevalence in oesophageal and gastric carcinoma patients: a population-based study. Eur J Gastroenterol Hepatol 2004; 16: 681-688
• 30 Coughlin SS, Calle EE, Teras LR et al. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol 2004; 159: 1160-1167
• 31 Batty GD, Shipley MJ, Marmot M et al. Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study. Cancer Causes Control 2004; 15: 873-881
• 32 Zendehdel K, Nyren O, Ostenson CG et al. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 2003; 95: 1797-1800
• 33 Verlato G, Zoppini G, Bonora E et al. Mortality from site-specific malignancies in type 2 diabetic patients from Verona. Diabetes Care 2003; 26: 1047-1051
• 34 Koskinen SV, Reunanen AR, Martelin TP et al. Mortality in a large population-based cohort of patients with drug-treated diabetes mellitus. Am J Public Health 1998; 88: 765-770
• 35 Wideroff L, Gridley G, Mellemkjaer L et al. Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 1997; 89: 1360-1365
• 36 La Vecchia C, Negri E, Franceschi S et al. A case-control study of diabetes mellitus and cancer risk. Br J Cancer 1994; 70: 950-953
• 37 Adami HO, McLaughlin J, Ekbom A et al. Cancer risk in patients with diabetes mellitus. Cancer Causes Control 1991; 2: 307-314
• 38 Ragozzino M, Melton 3rd LJ, Chu CP et al. Subsequent cancer risk in the incidence cohort of Rochester, Minnesota, residents with diabetes mellitus. J Chronic Dis 1982; 35: 13-19
• 39 Tseng CH. Diabetes conveys a higher risk of gastric cancer mortality despite an age-standardised decreasing trend in the general population in Taiwan. Gut 2011; 60: 774-779
• 40 Yoshizawa N, Yamaguchi H, Yamamoto M et al. Gastric carcinogenesis by N-Methyl-N-nitrosourea is enhanced in db/db diabetic mice. Cancer Sci 2009; 100: 1180-1185
• 41 Fox JG, Wang TC. Inflammation, atrophy, and gastric cancer. J Clin Invest 2007; 117: 60-69
• 42 Greenfield JR, Campbell LV. Relationship between inflammation, insulin resistance and type 2 diabetes: ‘cause or effect’?. Curr Diabetes Rev 2006; 2: 195-211
• 43 Sasco AJ, Secretan MB, Straif K. Tobacco smoking and cancer: a brief review of recent epidemiological evidence. Lung Cancer 2004; 45 (Suppl. 02) S3-S9
• 44 Yang P, Zhou Y, Chen B et al. Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur J Cancer 2009; 45: 2867-2873
• 45 Helicobacter, Cancer Collaborative G . Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001; 49: 347-353
• 46 Greenland S, Neutra R. An analysis of detection bias and proposed corrections in the study of estrogens and endometrial cancer. J Chronic Dis 1981; 34: 433-438
• 47 Chodick G, Heymann AD, Rosenmann L et al. Diabetes and risk of incident cancer: A large population-based cohort study in Israel. Cancer Causes and Control 2010; 21: 879-887