Statins associate with lower risk of biliary tract cancers: A systematic review and meta‐analysis

Abstract

Background Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. Methods PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta‐Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random‐effects model. Results Eight observational studies (3 cohort and 5 case–control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0–71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51–0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38–0.94) and GBC was 0.78 (95% CI: 0.68–0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66–1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69–0.88) and 0.70 (95% CI: 0.61–0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non‐steroidal anti‐inflammatory drugs (aRR: 0.80, 95% CI: 0.72–0.89) and metformin (aRR: 0.80, 95% CI: 0.72–0.90). Conclusions Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.

Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study

“…Liu et al reported that statin use was associated with a nearly 12% lower risk of bile duct cancer (OR = 0.88, 95% CI: 0.79-0.98), compared with non-use of statins. Meanwhile, the latest metaanalysis based on eight observational studies also supported this correlation (Cheung et al, 2023). Conversely, from the same European population, the team of Tran et al (Tran et al, 2020) yielded the benefits role of statin use in liver cancer prevention (OR = 0.48, 95% CI: 0.24-0.94) but not in bile duct cancer (HR = 1.09, 95% CI: 0.45-2.64).…”

“…Statins, the inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase (HMGCR), are commonly used as lipid-lowering drugs for atherosclerosis ( Ziaeian and Fonarow, 2017 ). Recently, statins have also received increasing attention owing to the rate-limiting enzyme in the mevalonate pathway (a pathway controlling a range of cell signaling molecules with the potential to regulate carcinogenesis) for cancer prevention ( Saka-Herrán et al, 2022 ; Khazaaleh et al, 2022 ; Zhang et al, 2019 ; Longo et al, 2022 ; Cheung et al, 2023 ) ( Figure 1 ). Detailly, preclinical research revealed that statins might inhibit the cancer cell proliferation via countering the cell cycle at the G1-S phase and enhancing the cell apoptosis ( Ahmadi et al, 2017 ).…”

Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population

“…Several previous meta-analyses have suggested that statin use decreases the esophageal cancer 20 , stomach cancer risk 21 , colorectal cancer 22 , biliary trace cancer 23 , and prostate cancer 24 . On the contrary, significant associations of these cancers with the long-term use of anti-cholesterol drugs were not observed in this study.…”

Statins: Are Lipid-lowering Drugs Useful in Sarcomas?

“…Viability and apoptosis are on lipophilicity, in osteosarcoma [24], chondrosarcoma [41], or rhabdomyosarcoma [43], but no clinical data related to the differential effect of lipophilic vs hydrophilic statin in sarcomas were found. Data from other types of tumors show this action [80], being lipophilic statins more effective.…”