Cancer Res Treat.  2016 Apr;48(2):798-805. 10.4143/crt.2015.117.

Long-Term Low-Dose Aspirin Use Reduces Gastric Cancer Incidence: A Nationwide Cohort Study

• Kim YI
• Kim SY
• Kim JH
• Lee JH
• Kim YW
• Ryu KW
• Park JH
• Choi IJ

• KMID: 2454358
• DOI: http://doi.org/10.4143/crt.2015.117

Abstract

PURPOSE
The aim of this study was to investigate whether aspirin use can reduce the incidence of gastric cancer in patients with hypertension or type 2 diabetes.
MATERIALS AND METHODS
A total of 200,000 patients with hypertension or type 2 diabetes were randomly selected from the Korean National Health Insurance claim database. Of these, 3,907 patients who used 100 mg of aspirin regularly (regular aspirin users) and 7,808 patients who did not use aspirin regularly (aspirin non-users) were selected at a frequency of 1:2, matched by age, sex, comorbid illnesses (type 2 diabetes and hypertension), and observation periods. The incidence of gastric cancer in this cohort was then assessed during the observation period of 2004 to 2010.
RESULTS
In the matched cohort, the incidence rates of gastric cancer were 0.8% (31/3,907) for regular aspirin users and 1.1% (86/7,808) for aspirin non-users, but the cumulative incidence rates were not significantly different between groups (p=0.116, log-rank test). However, in multivariate analysis, regular aspirin users had a reduced risk of gastric cancer (adjusted hazard ratio [aHR], 0.71; 95% confidential interval [CI], 0.47 to 1.08; p=0.107). Duration of aspirin use showed significant association with reduction of gastric cancer risk (aHR for each year of aspirin use, 0.85; 95% CI, 0.73 to 0.99; p=0.044), particularly in patients who used aspirin for more than 3 years (aHR, 0.40; 95% CI, 0.16 to 0.98; p=0.045).
CONCLUSION
Long-term low-dose aspirin use was associated with reduced gastric cancer risk in patients with hypertension or type 2 diabetes.

Keyword

Aspirin; Low-dose; Stomach neoplasms; Risk

MeSH Terms

Aspirin*
Cohort Studies*
Humans
Hypertension
Incidence*
Multivariate Analysis
National Health Programs
Stomach Neoplasms*
Aspirin

Figure

• 

  Fig. 1. Study flowchart. Patients with hypertension or type 2 diabetes (100,000 patients each) were classified as aspirin users or non-users. Non-users were matched with users based on demographic and comorbidity covariates. KNHI, Korean National Health Insurance; NSAIDs, non-steroidal anti-inflammatory drugs.

• 

  Fig. 2. Observation periods of aspirin users. Claims for aspirin use were investigated in all cohort patients from 2004-2010. For aspirin users, observation periods for gastric cancer began after 6 consecutive months of payment claims for aspirin and ended on 31 December 2010. Non-user observation periods began immediately after any claim was made for hypertension or diabetes. Duration of observation was matched between users and non-users to prevent sampling bias.

• 

  Fig. 3. Cumulative incidence of gastric cancer according to aspirin use. The cumulative gastric cancer incidence rate in aspirin users was not statistically different from that of non-users (p=0.116, log-rank test).

Reference

References

1. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013; 31:1281–357.

2. Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care. 2010; 33:1395–402.

3. Kune GA, Kune S, Watson LF. Colorectal cancer risk, chronic illnesses, operations, and medications: case control results from the Melbourne Colorectal Cancer Study. Cancer Res. 1988; 48:4399–404.

4. Bosetti C, Rosato V, Gallus S, Cuzick J, La Vecchia C. Aspirin and cancer risk: a quantitative review to 2011. Ann Oncol. 2012; 23:1403–15.

5. Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol. 2012; 13:518–27.

6. Sostres C, Lanas A. Gastrointestinal effects of aspirin. Nat Rev Gastroenterol Hepatol. 2011; 8:385–94.

7. Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer. 2006; 6:130–40.

8. Cheng J, Fan XM. Role of cyclooxygenase-2 in gastric cancer development and progression. World J Gastroenterol. 2013; 19:7361–8.

9. Rosenbaum PR, Rubin DB. Constructing a control group using multivariate matched sampling methods that incorporate the propensity score. Am Stat. 1985; 39:33–8.

10. World Health Organization. ICD-10: International statistical classification of diseases and related health problems. 10th rev. Geneva: World Health Organization;1992.

11. Farrow DC, Vaughan TL, Hansten PD, Stanford JL, Risch HA, Gammon MD, et al. Use of aspirin and other nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev. 1998; 7:97–102.

12. Langman MJ, Cheng KK, Gilman EA, Lancashire RJ. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ. 2000; 320:1642–6.

13. Akre K, Ekstrom AM, Signorello LB, Hansson LE, Nyren O. Aspirin and risk for gastric cancer: a population-based case-control study in Sweden. Br J Cancer. 2001; 84:965–8.

14. Fortuny J, Johnson CC, Bohlke K, Chow WH, Hart G, Kucera G, et al. Use of anti-inflammatory drugs and lower esophageal sphincter-relaxing drugs and risk of esophageal and gastric cancers. Clin Gastroenterol Hepatol. 2007; 5:1154–9.

15. Duan L, Wu AH, Sullivan-Halley J, Bernstein L. Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric adenocarcinomas in Los Angeles County. Cancer Epidemiol Biomarkers Prev. 2008; 17:126–34.

16. Schreinemachers DM, Everson RB. Aspirin use and lung, colon, and breast cancer incidence in a prospective study. Epidemiology. 1994; 5:138–46.

17. Lindblad M, Lagergren J, Garcia Rodriguez LA. Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14:444–50.

18. Abnet CC, Freedman ND, Kamangar F, Leitzmann MF, Hollenbeck AR, Schatzkin A. Non-steroidal anti-inflammatory drugs and risk of gastric and oesophageal adenocarcinomas: results from a cohort study and a meta-analysis. Br J Cancer. 2009; 100:551–7.

19. Epplein M, Nomura AM, Wilkens LR, Henderson BE, Kolonel LN. Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study. Am J Epidemiol. 2009; 170:507–14.

20. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G. Aspirin, salicylates, and cancer. Lancet. 2009; 373:1301–9.

21. Lim HY, Joo HJ, Choi JH, Yi JW, Yang MS, Cho DY, et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin Cancer Res. 2000; 6:519–25.

22. Kim JY, Lee HS, Kim N, Shin CM, Lee SH, Park YS, et al. Prevalence and clinicopathologic characteristics of gastric cardia cancer in South Korea. Helicobacter. 2012; 17:358–68.

23. Cho SJ, Choi IJ, Kim CG, Lee JY, Kook MC, Seong MW, et al. Helicobacter pylori seropositivity is associated with gastric cancer regardless of tumor subtype in Korea. Gut Liver. 2010; 4:466–74.

24. Yim JY, Kim N, Choi SH, Kim YS, Cho KR, Kim SS, et al. Seroprevalence of Helicobacter pylori in South Korea. Helicobacter. 2007; 12:333–40.

25. Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010; 19:1893–907.