Aspirin, non-aspirin NSAID, acetaminophen use and ovarian cancer risk

NCI Intramural funding

Ovarian cancer has a poorly understood etiology and natural history and is the most common cause of death among women who develop gynecologic malignancies and the fifth leading cause of cancer death in females in the United States. Although relatively uncommon, afflicting about 1 in 60 women in USA, the high mortality rate makes the disease a major health concern. Thus, strategies that focus on prevention may provide the most rational approach for meaningful reductions in deaths attributable to ovarian cancer.

Epidemiological evidence suggests that ovarian cancer may be related to chronic inflammation. Inhibition of COX-1 and COX-2 enzymes in the synthesis of prostaglandins is thought to be the major mechanism responsible for the anti-inflammatory and anti-neoplastic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, NSAIDs may suppress ovulation and affect cell proliferation, angiogenesis, and apoptosis of the epithelium. Acetaminophen, another commonly used analgesic and antipyretic drug, has weak anti-inflammatory activity and may have an anti-gonadotropic effect. It has also been proposed that acetaminophen inhibits ovarian carcinogenesis through the depletion of glutathione leading to necrosis. Therefore, aspirin, acetaminophen or NSAIDs may be potential agents for the chemoprevention of ovarian cancer. Because of the widespread use of aspirin, acetaminophen, and NSAIDs, any association with an increased or decreased cancer risk may have important public health implications.

Several studies have described an association between aspirin or other NSAIDs use and the risk of ovarian cancer, with inconsistent results. In our recent pooled analysis of 12 ovarian cancer case-control studies participating in the Ovarian Cancer Association Consortium (OCAC) we reported a reduced risk of ovarian cancer with aspirin use, especially among daily users of low dose aspirin. Confirming the association between aspirin use and epithelial ovarian cancer in larger prospective datasets is crucial to better understanding the biology behind tumor development as well as improving potential prevention recommendations for women who may be at increased risk of ovarian cancer. However, since individual cohort studies have limited samples size, especially for subgroup analyses, it is only by pooling data across a number of large cohorts that this research will be feasible.

The objective of this study will be to examine the association between aspirin, acetaminophen, or non-aspirin NSAID use and ovarian cancer risk using individual-level data from studies participating in the Ovarian Cancer Cohort Consortium (OC3).

1. Evaluate association between aspirin, acetaminophen, or non-aspirin NSAID use and ovarian cancer risk.
2. Evaluate association between aspirin, acetaminophen, or non-aspirin NSAID use and risk of major histologic subtypes of epithelial ovarian cancer.

Full cohort analysis using cox proportional hazards regression with a strata term for cohort.

Evaluate association in cohort reduces potential for recall bias that is inherent in case-control studies, individual cohorts not powered for modest risk reductions, individual cohorts do not have sufficient case numbers to evaluate associations by histologic type.

50

Incident cases of invasive epithelial ovarian cancer (including fallopian tube and primary peritoneal cancers). Data on histologic subtype, tumor dominance, stage and grade, if available.

Anti-inflammatory drug use (ever vs. never, duration, amount, type, indication, e.g., aspirin, non-aspirin NSAIDs, acetaminophen)

Risk factors for ovarian cancer, including reproductive variables (age at menarche, parity, age a first full-term pregnancy, infertility, age at menopause, type of menopause, use of oral contraceptives, use of menopausal hormone therapy), anthropometry, gynecological surgery (tubal ligation, hysterectomy, unilateral/bilateral oophorectomy), first degree family history of breast and ovarian cancer

No