Non-steroidal anti-inflammatory drugs and endometrial cancer risk in the VITamins And Lifestyle (VITAL) cohort
ABSTRACT OBJECTIVE: Chronic inflammation may be an important factor in the initiation and promotion of endometrial cancer. Use of non-steroidal anti-inflammatory drugs (NSAIDs), however, has been inconsistently associated with endometrial cancer risk. METHODS: 22,268 female residents of western Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10years. Use was categorized as none, low (<4days/week or <4years), and high (≥4days/week and ≥4years). Over 9years of follow-up, 262 incident invasive endometrial cancers were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Relative to non-use, high use of aspirin was inversely associated with endometrial cancer risk (HR 0.64, 95% CI: 0.41-1.01; P trend=0.03). Findings were stronger for regular-strength than low-dose aspirin. High use of non-aspirin NSAIDs (HR 1.15, 95% CI: 0.68-1.95), including ibuprofen (HR 1.29, 95% CI: 0.73-2.28), and naproxen (HR 1.08, 95% CI: 0.39-2.95) was not associated with risk. In subgroup analyses, findings for aspirin were strongest for cancers of endometrioid histology and were restricted to non-smokers. CONCLUSIONS: This study provides additional evidence that use of aspirin, but not non-aspirin NSAIDs, may reduce the risk of endometrial cancer, especially in estrogen-mediated cases; however additional prospective studies with high-quality measurement of NSAID use are needed. Aspirin should continue to be examined as a potential agent for cancer chemoprevention.
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ABSTRACT: Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes. Although LS is associated with increased risk for developing colorectal, endometrial and other cancers, specialized screening, risk-reducing surgery, and chemoprevention offer promise for reducing morbidity and mortality. Frequent colonoscopic surveillance has proven effective for early detection and prevention of LS-associated colorectal cancer (CRC); however, the optimal strategy for managing endometrial cancer risks in women with germline mutations in DNA mismatch repair genes has yet to be determined. In this issue of the journal, Lu et al. report their findings of a Phase II prospective, multicenter randomized trial comparing the effects of oral contraceptive pills and Depo-Provera on endometrial proliferation in women with LS. Although short-term hormonal treatment with either modality altered endometrial proliferation indices, it remains unknown whether hormonal suppression actually reduces endometrial cancer risk in women with LS. This trial represents the first of its kind in evaluating agents which might offer protection against LS-associated endometrial cancer and provides preliminary data regarding potential biomarkers for early detection of endometrial neoplasia. However, the investigators' experience with this trial also offers insights regarding the various technical and scientific challenges inherent in chemoprevention research.Cancer Prevention Research 07/2013; 6(8). DOI:10.1158/1940-6207.CAPR-13-0238 · 5.27 Impact Factor
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ABSTRACT: Inflammation plays an important role in endometrial cancer etiology. Long-chain ω-3 (n-3) polyunsaturated fatty acids (PUFAs), derived from marine sources, are thought to be antiinflammatory; however, several studies of fish consumption suggest an increase in risk. This study examined whether intakes of long-chain ω-3 PUFAs, including eicosapentaenoic acid (EPA; 20:5ω-3) and docosahexaenoic acid (DHA; 22:6ω-3), from diet and supplements and intake of fish are associated with endometrial cancer risk. Between 2000 and 2002, 22,494 women aged 50-76 y, living in western Washington State, were recruited to the VITamins And Lifestyle cohort study. Incident endometrial cancers (n = 263) were identified through the Surveillance, Epidemiology, and End Results cancer registry after 9 y of follow-up. Multivariable-adjusted HRs and 95% CIs for the association of intakes of individual long-chain ω-3 PUFAs and fish with endometrial cancer risk were estimated by using Cox proportional hazards. Women in the highest compared with the lowest quintile of dietary EPA + DHA intake had a 79% increased risk of endometrial cancer (95% CI: 16%, 175%; P-trend = 0.026). Results were similar for EPA and DHA measured individually and for fish intake. When data were stratified by body mass index (in kg/m(2); <25 or ≥25), increases in risk of long-chain ω-3 PUFAs were restricted to overweight and obese women, and statistically significant reductions in risk were observed for normal-weight women. The overall increased risk reported here confirms the findings of several prior observational studies of fish intake, which observed similar increases in risk. Randomized trials are needed to confirm these findings.American Journal of Clinical Nutrition 02/2014; 99(3). DOI:10.3945/ajcn.113.070524 · 6.92 Impact Factor
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ABSTRACT: Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n-3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk. We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype. Women were n = 87,360 participants of the Women's Health Initiative Observational Study and Clinical Trials who were aged 50-79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk. Intakes of individual LCω-3PUFAs were associated with 15-23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m(2)) <25, those in the upper compared with lowest quintiles of total LCω-3PUFA intake (sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) had significantly reduced endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers.Conclusions: Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that used biomarkers of ω-3 intake are needed to more-accurately estimate their effects on endometrial cancer risk. This trial was registered at clinicaltrials.gov as NCT00000611. © 2015 American Society for Nutrition.American Journal of Clinical Nutrition 03/2015; 101(4). DOI:10.3945/ajcn.114.098988 · 6.92 Impact Factor