Low-dose aspirin protects against ovarian cancer
Regular use of low-dose aspirin appears to protect against ovarian cancer risk, according to a recent study, which also reports that such risks may be exacerbated in those with long-term, high-quantity use of other analgesics.
Researchers enrolled 93,664 women (mean age 45.9±7.2 years) from the Nurses’ Health Study (NHS) and 111,834 (mean age 34.2±4.7 years) from the NHS II in whom the patterns of analgesic use (type, timing, duration, frequency and number of tablets used) were assessed. Biennial, self-accomplished questionnaires were used to identify cases of ovarian cancer.
A total of 1,054 incident cases of epithelial ovarian cancer was documented over 1,779,572 and 1,884,999 person-years of follow-up in NHS and NHS II cohorts, respectively. Total current use of low- and standard-dose aspirin was not significantly associated with the risk of ovarian cancer (hazard ratio [HR], 0.99; 95 percent CI, 0.83–1.19). [JAMA Oncol 2018;doi:10.1001/jamaoncol.2018.4149]
There was likewise no relationship between the duration of aspirin medication (≥15 years vs 1 year: HR, 1.13; 0.91–1.39; p=0.22 for trend) or cumulative average tablets per week (≥10 tablet vs <1 tablet: HR, 1.02; 0.78–1.33; p=0.65) and ovarian cancer risk.
Women with high cumulative average frequency of aspirin use tended to have a lower risk of ovarian cancer, but significance was not achieved (≥5 vs <2 days per week: HR, 0.86; 0.66–1.12; p=0.52 for trend).
However, when low-dose and standard-dose aspirin use was analysed separately, researchers found a significant protective effect associated with current low-dose aspirin use relative to nonuse (HR, 0.77; 0.61–0.96). This effect was absent in current standard-dose aspirin use (HR, 1.17; 0.92–1.49).
Moreover, a longer duration (≥5 years vs <1 year) of low-dose aspirin use was not associated with ovarian cancer risk (HR, 0.92; 0.57–1.48; p=0.41 for trend), but was for standard-dose aspirin use (HR, 1.77; 1.13–2.77; p=0.004 for trend).
Inflammation is the primary pathway by which aspirin is thought to suppress the risk of cancer, explained researchers. For instance, in previous studies, it was shown that in cutting the risk of colon cancer, aspirin interfered with the synthesis of prostaglandin through the inhibition of the cyclooxygenase (COX) 1 and 2 enzymes. [Nat Rev Cancer 2006;6;130-140; Semin Oncol 2016;43:65-77]
“We did not observe a dose-response relationship for ovarian cancer, suggesting that other mechanisms may be driving the association,” they added, indicating that at low doses, aspirin may act through unique mechanisms that affect carcinogenesis.
Notably, researchers also showed that there was a significant and positive association between the risk of ovarian cancer and the current use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs; HR, 1.19; 1.00–1.41). Prolonged NSAID use (≥10 years) had the same effect (HR, 1.34; 1.05–1.70; p=0.02 for trend).
On the other hand, current acetaminophen use had no effect on ovarian cancer risk (HR, 1.02; 0.86–1.21), as did heavy use (≥2,500 tablet-days: HR, 1.41; 0.99–2.00; p=0.10 for trend).
That the three medications share only parts of their mechanisms of action may account for the observed differences in effect, researchers explained. “For example, although aspirin, nonaspirin NSAIDs and acetaminophen can block the COX enzymes, the extent to which they each block COX-1 and COX-2 differs.” [Nat Rev Cancer 2006;6;130-140]
“To our knowledge, this prospective cohort study is among the first to evaluate in detail the associations between type, timing, frequency, quantity and duration of analgesic use with risk of ovarian cancer by using regularly updated exposure information,” they said.
Further studies should focus on elucidating the mechanisms underlying the relationship between analgesic use and ovarian cancer risk, particularly in heavy users, they added.