Use of Nonsteroidal Antiinflammatory Agents and Incidence of Ovarian Cancer in 2 Large Prospective Cohorts

Pinheiro, Simone P.; Tworoger, Shelley S.; Cramer, Daniel W.; Rosner, Bernard; Hankinson, Susan E.

doi:10.1093/aje/kwp062

Cited by 41 publications

(58 citation statements)

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“…Compared to women who reported no use of aspirin, the relative risks of OC for those who used aspirin < 2, 2–5 times, and ≥ 6 times per week were 0.83, 0.77, and 0.61, respectively ( P =0.04) but no association was observed between NSAID use and risk. Conversely, in the NHS I and II 338 regular use of NSAIDS was protective (HR=0.81, 95% CI: 0.64–1.01) but aspirin use was not (HR=1.11, 95% CI: 0.92–1.33). No dose-response relationship with increased frequency or duration of use was observed, and results did not differ when stratifying by tumor histology 338 .…”

Section: Risk Factors and Preventive Factorsmentioning

confidence: 91%

“…Conversely, in the NHS I and II 338 regular use of NSAIDS was protective (HR=0.81, 95% CI: 0.64–1.01) but aspirin use was not (HR=1.11, 95% CI: 0.92–1.33). No dose-response relationship with increased frequency or duration of use was observed, and results did not differ when stratifying by tumor histology 338 . A recent pooled analysis of 12 case-control studies in the OCAC 340 found aspirin use was associated with a reduced risk of OC (OR=0.91, 95% CI: 0.84–0.99), especially among daily users of low-dose (<100 mg) aspirin (OR=0.66, 95% CI: 0.53–0.83).…”

Section: Risk Factors and Preventive Factorsmentioning

confidence: 91%

“…In addition, animal and in vitro studies suggest aspirin inhibits the growth of OC 335-337 . Several prospective 338,339 and case-control 340-344 studies have observed an inverse association between aspirin and nonsteroidal anti-inflammatory drugs (NSAIDS) and OC incidence, though other studies have reported no association 345,346 . Prizment and colleagues 339 investigated these drugs using data from a prospective cohort of approximately 20,000 women from the Iowa Women’s Health Study.…”

Section: Risk Factors and Preventive Factorsmentioning

confidence: 99%

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Epidemiology of ovarian cancer: a review

Reid

Permuth

Sellers

2017

Cancer Biology &Amp; Medicine

1,107

403

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Ovarian cancer (OC) is the seventh most commonly diagnosed cancer among women in the world and the tenth most common in China. Epithelial OC is the most predominant pathologic subtype, with five major histotypes that differ in origination, pathogenesis, molecular alterations, risk factors, and prognosis. Genetic susceptibility is manifested by rare inherited mutations with high to moderate penetrance. Genome-wide association studies have additionally identified 29 common susceptibility alleles for OC, including 14 subtype-specific alleles. Several reproductive and hormonal factors may lower risk, including parity, oral contraceptive use, and lactation, while others such as older age at menopause and hormone replacement therapy confer increased risks. These associations differ by histotype, especially for mucinous OC, likely reflecting differences in etiology. Endometrioid and clear cell OC share a similar, unique pattern of associations with increased risks among women with endometriosis and decreased risks associated with tubal ligation. OC risks associated with other gynecological conditions and procedures, such as hysterectomy, pelvic inflammatory disease, and polycystic ovarian syndrome, are less clear. Other possible risk factors include environmental and lifestyle factors such as asbestos and talc powder exposures, and cigarette smoking. The epidemiology provides clues on etiology, primary prevention, early detection, and possibly even therapeutic strategies.

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Section: Risk Factors and Preventive Factorsmentioning

confidence: 91%

Section: Risk Factors and Preventive Factorsmentioning

confidence: 91%

Section: Risk Factors and Preventive Factorsmentioning

confidence: 99%

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Epidemiology of ovarian cancer: a review

Reid

Permuth

Sellers

2017

Cancer Biology &Amp; Medicine

1,107

403

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“… A: Forest plot summarizing individual effect estimates from fourteen studies contributing to pooled effect estimates for ovarian cancer risk in aspirin users [5,8,20,7,6,9,10,12,13,15,14,19,21]…”

Section: Figure Imentioning

confidence: 99%

“…These analyses did not show a significant association between the use of NSAIDs and ovarian cancer; however, relevant findings from at least five additional case-control studies [10,12,13,15,14], two cohort studies [20,21] and one clinical trial [24] have been published, with heterogeneous results.…”

Section: Introductionmentioning

confidence: 97%

Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review

Murphy

Trabert

Yang

et al. 2012

Cancer Causes Control

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Background Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent. Methods We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with “regular use” of NSAIDs in previously published studies. Results We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95% CI 0.87–1.29; non-aspirin NSAIDs: RR 0.93, 95% CI 0.74–1.15); however summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95% CI 0.77–1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95% CI 0.23–2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50–0.94.) Conclusion Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.

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Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies

et al. 2018

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Importance: Ovarian cancer is a highly fatal malignancy with few modifiable risk factors. Results from case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin. We sought to confirm these findings in a large, prospective study with detailed information on NSAID use. Objective: To evaluate whether regular aspirin or non-aspirin NSAID use, and patterns of use, are associated with lower ovarian cancer risk. Design: We included women from two prospective cohorts, the Nurses’ Health Study (NHS) and NHSII. Setting: NHS/NHSII participants were followed 1980–2014 (NHS) and 1989–2015 (NHSII). Participants: Participants in NHS (N=93,664) and NHSII (N=111,834), including 1054 cases of incident epithelial ovarian cancer. Exposures: For each analgesic type, aspirin, low-dose aspirin, non-aspirin NSAIDs and acetaminophen, we evaluated timing, duration, frequency, and number of tablets used; exposure information was updated every 2–4 years. Main Outcome(s) and Measure(s): We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of aspirin, non-aspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were two-sided, with a significance level of 0.05. Results: We did not observe significant associations between aspirin and ovarian cancer risk when we evaluated current versus non-use of any aspirin, regardless of dose (HR=0.99, 95%CI=0.83–1.19). However, when we evaluated low-dose (≤100mg) and standard-dose (325mg) aspirin separately, we observed an inverse association for low-dose aspirin (HR=0.77, 95%CI=0.61–0.96), but no association for standard-dose aspirin (HR=1.17, 95%CI=0.92–1.49). Current use of non-aspirin NSAIDs was positively associated with risk of ovarian cancer compared to non-use (HR=1.19, 95%CI=1.00–1.41), and we observed significant positive trends for duration of use (p-trend=0.02) and cumulative average tablets per week (p-trend=0.03). There were no clear associations for acetaminophen. Conclusions and Relevance: Our results were consistent with case-control studies showing a reduced risk of ovarian cancer among regular users of low-dose aspirin. We observed an increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly non-aspirin NSAIDs, though this finding requires confirmation.

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Use of Nonsteroidal Antiinflammatory Agents and Incidence of Ovarian Cancer in 2 Large Prospective Cohorts

Cited by 41 publications

References 50 publications

Epidemiology of ovarian cancer: a review

Epidemiology of ovarian cancer: a review

Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review

Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies

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