The association between statins and colorectal cancer stage in the Women's Health Initiative

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.

The effects of statins in patients with advanced-stage cancers - a systematic review and meta-analysis

“…Possible reasons include that these trials were designed to estimate the improvement in the effectiveness of other first-line drugs, not the effectiveness of statins alone, and more RCTs are needed to validate the robustness of our findings. In addition, accumulating data suggested that lipophilic statins provide a stronger protective effect than hydrophilic statins (63)(64)(65). However, the hydrophilic group displayed a lower hazard ratio in this study, probably because that most of the observational studies did not clarify statin types in their studies, which limited the number of included studies in this subgroup analysis.…”

Effects of statins on brain tumors: a review

“…The inhibition of isoprenoids synthesis mediated by statins also contributes to apoptosis induction and prevents the development of the cell cycle in different types of cancer cells [28]. In many cancers, including melanoma, extrahepatic cholangiocarcinoma, pancreatic adenocarcinoma, non-muscle-invasive bladder cancer, hepatocellular carcinoma, thymic carcinoma, renal cell carcinoma, and in breast, colorectal, liver, lung, and prostate cancers, the effects of statins on cancer risk, recurrence and survival have been confirmed in preclinical and clinical studies [29][30][31][32][33][34][35][36][37]; however, some of the large-scale reviews, including systematic review and meta-analysis, have not clearly shown any beneficial impact of statins against cancer [38][39][40].…”