Abstract
The anticarcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’, with users more likely diagnosed with early rather than late stage cancer. The association between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women's Health Initiative (WHI) was investigated. The study population included 132,322 post-menopausal women, among which there were 2,628 pathologically confirmed cases of
in situ
(3.3%), localized (43.6%), regional (40.4%) and distant (12.7%) stage CRC, after an average of 13.9 (SD=4.7) years of follow-up. To reduce the possibility of detection bias among women more likely to be prescribed statins, women who did not report a mammogram within 5 years of study entry and who had no health insurance or medical care provider (n=28,237) were excluded from the study. Stage was coded using SEER criteria into early (
in situ
and local) vs. late (regional and distant) stage disease. Hazards ratios (HR) and 95% confidence intervals (CIs) evaluating the association between statin use and diagnosis of late-stage CRC both at baseline and in a time-dependent manner were computed from multivariable-adjusted Cox proportional hazards analyses. In the multivariable time-dependent analysis, there was a lower hazard of late stage CRC among users of lipophilic statins compared with non-users (HR=0.80, 95% CI 0.66-0.98, P=0.029) and a marginally lower hazard of late stage CRC among users of lipophilic vs. hydrophilic statins (HR=0.70, 95% CI 0.49-1.01, P=0.058). The use of lipophilic statins was associated with a reduction in the proportion of CRC cases that were late stage at the time of diagnosis.