Statin use and risk of liver cancer: an update meta-analysis

Shi, Meng; Zheng, Hongchen; Nie, Biao; Gong, Wei; Cui, Xiaobing

doi:10.1136/bmjopen-2014-005399

Cited by 67 publications

(60 citation statements)

References 51 publications

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“…Moreover, in human statins treatments modify in vivo immune cells response by decreasing inflammatory cytokines concentration, increasing CD8+ T cells frequency and T lymphocytes activation . Additionally, retrospective studies have shown that statins can also have a protective effect against the development of cancers, particularly melanomas and liver cancers . Since 16 years, different farnesyl transferase inhibitors (FTI) have been evaluated during clinical trials demonstrating a limited anti‐tumor activity in hematologic cancers and no therapeutic efficiency in solid tumors treatment .…”

Section: Statins and Pharmacological Inhibitors Of Rho Gtpases Prenylmentioning

confidence: 99%

Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti‐melanoma immune response

Sarrabayrouse

Pich-Bavastro

Teiti

et al. 2016

Intl Journal of Cancer

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Melanoma is a highly lethal cutaneous tumor, killing affected patients through development of multiple poorly immunogenic metastases. Suboptimal activation of immune system by melanoma cells is often due to molecular modifications occurring during tumor progression that prevent efficient recognition of melanoma cells by immune effectors. Statins are HMG-CoA reductase inhibitors, which block the mevalonate synthesis pathway, used by millions of people as hypocholesterolemic agents in cardiovascular and cerebrovascular diseases. They are also known to inhibit Rho GTPase activation and Rho dependent signaling pathways. Rho GTPases are regarded as molecular switches that regulate a wide spectrum of cellular functions and their dysfunction has been characterized in various oncogenic process notably in melanoma progression. Moreover, these molecules can modulate the immune response. Since 10 years we have demonstrated that Statins and other Rho GTPases inhibitors are critical regulators of molecules involved in adaptive and innate anti-melanoma immune response. In this review we summarize our major observations demonstrating that these pharmacological agents stimulate melanoma immunogenicity and suggest a potential use of these molecules to promote anti-melanoma immune response.

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Section: Statins and Pharmacological Inhibitors Of Rho Gtpases Prenylmentioning

confidence: 99%

Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti‐melanoma immune response

Sarrabayrouse

Pich-Bavastro

Teiti

et al. 2016

Intl Journal of Cancer

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“…Data safety analyses of early randomized controlled trials of statins revealed an inverse association between statin use and cancer incidence . Preclinical studies have demonstrated growth‐suppressive effects on various tumors, and epidemiologic studies have shown inverse associations with overall cancer risk and the risk of other gastrointestinal cancers, including esophageal, colorectal, and liver cancer …”

Section: Introductionmentioning

confidence: 99%

“…6 Preclinical studies have demonstrated growth-suppressive effects on various tumors, and epidemiologic studies have shown inverse associations with overall cancer risk 7,8 and the risk of other gastrointestinal cancers, including esophageal, 9 colorectal, 10 and liver cancer. 11 Previous studies of statin use and PC risk are inconsistent. Some randomized controlled trials and cohorts were underpowered, [12][13][14][15][16][17] and among nontrial studies, 7,[18][19][20][21][22][23][24][25][26] few examined associations by sex with the exception of a large study of predominantly male veterans 26 and a UK study 19 in which inverse relationships were observed only in men and male smokers, respectively.…”

Section: Introductionmentioning

confidence: 99%

Statin use and risk of pancreatic cancer: Results from a large, clinic‐based case‐control study

Walker

Holly

et al. 2015

Cancer

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Background Statins are cholesterol-lowering medications with pleiotropic effects including alterations in growth signaling as well as immunomodulatory and anti-inflammatory effects that may alter cancer risk. Evidence from previous epidemiologic studies is inconsistent regarding whether statin use is associated with reduced risk of pancreatic cancer (PC). Methods Patients with confirmed diagnoses of PC (cases) were recruited from medical and surgical oncology clinics, with controls (frequency-matched by sex and age) recruited from general medicine clinics, at a high-volume academic medical center over a six-year period (2006–2011). Direct interviews were conducted using an epidemiological risk factor questionnaire covering topics such as medical history, lifestyle factors, and medication usage. Adjusted multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (95%CI) as estimates of the relative risk of PC. Results Data were obtained from 536 cases and 869 controls. Ever use of statins was associated with 34% reduced PC risk (OR=0.66, 95%CI 0.47–0.92). In sex-stratified analyses, risk was statistically significantly reduced in men only (men: OR=0.50, 95%CI 0.32–0.79; women: OR=0.86, 95%CI 0.52–1.43). Duration of use was inversely associated with PC risk (>10 year use: OR=0.51 overall; in men, OR=0.41, 95%CI 0.21–0.80; ptrend=0.006). Conclusions This is the largest case-control study to demonstrate an inverse association between statin use and PC risk. Risk reduction in statin users appears to be sex-specific and is more pronounced in long-term users. Further research is warranted to better characterize this association and clarify roles of underlying biologic mechanisms.

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“…Statins have been proposed to be beneficial in cancer prevention, including melanoma and cancer of the colon, breast and prostate as well as HCC . Statins are selectively distributed in the liver as target organ, and the majority of their beneficial effects appear to be mediated primarily by modulating lipid metabolism, mainly in the liver .…”

mentioning

confidence: 99%

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

Kim

Jang

Han

et al. 2016

Intl Journal of Cancer

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Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5-year HCC-free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22-0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14-0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32-1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose-dependent manner, especially in individuals with liver disease.

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Statin use and risk of liver cancer: an update meta-analysis

Cited by 67 publications

References 51 publications

Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti‐melanoma immune response

Regulatory properties of statins and rho gtpases prenylation inhibitiors to stimulate melanoma immunogenicity and promote anti‐melanoma immune response

Statin use and risk of pancreatic cancer: Results from a large, clinic‐based case‐control study

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case‐control study

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