Prolonged, Regular Aspirin Use Linked to Reduced Risk of Gastric Cancer in Women

Several recent systematic reviews have demonstrated an inverse relationship between aspirin use and the risk of gastric cancer.

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Based on 34 years of follow-up of two large U.S. cohorts, Massachusetts General Hospital researchers have confirmed that association, but only in women. Sohee Kwon, MD, MPH, formerly of the Clinical and Translational Epidemiology Unit in the Department of Medicine, Andrew T. Chan, MD, MPH, director of cancer epidemiology in the Mass General Cancer Center, chief of the Clinical and Translational Epidemiology Unit, vice chair for clinical research in the Division of Gastroenterology, and professor of Medicine at Harvard Medical School, and colleagues also report in Cancer Prevention Research (Phila) that the protection is related to the dosage and duration of aspirin use.

Methods

The researchers analyzed data on:

• 109,684 participants in the Nurses' Health Study, which in 1976 enrolled 121,700 U.S. female registered nurses ages 30 to 55
• 49,432 participants in the Health Professionals Follow-up Study, which in 1986 enrolled 51,529 male health professionals ages 40 to 75

Participants complete a questionnaire every two years to provide information on lifestyle factors, medical history and disease outcomes. When a participant reported a diagnosis of gastric cancer, study physicians blinded to aspirin use sought permission to review medical records to confirm the diagnosis and classify histology, tumor location, and Lauren classification (intestinal- or diffuse-type).

Main Analysis

After adjustment for numerous lifestyle and dietary factors:

• Women who used aspirin regularly (more than twice a week) had a significantly lower risk of gastric adenocarcinoma than women who were nonregular users (HR, 0.52; 95% CI, 0.37–0.73)
• Regular aspirin use was not associated with the risk among men
• The association between regular aspirin use and risk of gastric adenocarcinoma among women was not affected by anatomic location, Lauren classification, or whether the disease presented with lymph node involvement or metastases

Aspirin Dosage

Among women, the apparent benefit of aspirin use for gastric cancer for regular users compared with nonusers was substantially greater with increasing dose (P for trend=0.01):

• 0.5–1.5 standard tablets (325 mg) per week—adjusted HR (aHR), 0.72 (95% CI, 0.47–1.09) compared with <0.5 tablet per week
• 1.5 to <5 tablets per week—aHR, 0.71 (95% CI, 0.48–1.05)
• ≥5 tablets per week—aHR, 0.51 (95% CI, 0.31–0.84)

Among men, taking more than five standard tablets per week was inversely associated with gastric cancer (aHR, 0.85) but the relationship was not statistically significant.

Duration of Aspirin Use

Among women, the beneficial association between aspirin use and gastric cancer was stronger with longer duration (P for trend < 0.001):

• <5 years—aHR, 0.77 (95% CI, 0.50–1.18) compared with never-use
• 5 to <10 years—aHR, 0.99 (95% CI, 0.63–1.56)
• ≥10 years—aHR, 0.45 (95% CI, 0.29–0.69)

Among men, ≥10 years of aspirin use was associated with a lower risk of gastric cancer (aHR, 0.77), but again the reduction was not significant.

Why the Sex Difference?

Several factors might explain the heterogeneity in results between men and women:

• The male cohort was smaller and follow-up was shorter, which may have limited the ability to detect the effect of aspirin use by men
• More male than female aspirin users reported using low-dose aspirin for cardiovascular disease prevention; low doses may be less effective for cancer prevention
• Biological differences between men and women may influence the effect of aspirin on the risk of gastric cancer

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