Screening statins for possible carcinogenic risk: Up to 9 years of follow-up of 361,859 recipients

Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA, USA.
Pharmacoepidemiology and Drug Safety (Impact Factor: 2.94). 01/2008; 17(1):27-36. DOI: 10.1002/pds.1507
Source: PubMed


Determine the risk of cancer in statin users.
Risk of cancer in up to 9.4 years after first recorded receipt of statins was evaluated in subscribers of an integrated health care program in northern California. Statin use and cancer development were ascertained from the program's pharmacy records and cancer registry from August 1994 to December 2003.
Most of the 361,859 statin users received lovastatin, simvastatin or both. Results are presented from analyses with 2-year lag and use for over 5 years. Most of the observed associations were likely due to chance or confounding. The few associations that seemed less readily explainable were increased risk of cancers of the thyroid, esophagus and urinary tract and decreased risk of colon cancer in men. Increased risk of lung cancer was the only nominally statistically significant positive association in women and could be partially attributable to their smoking habits.
Overall this study provided no strong evidence of either causation or prevention of cancer by statins.

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    • "A cohort study of US veterans reported a 48% reduction in the risk of renal cell carcinoma (RCC) associated with statin use [10], and two small population-based cohort studies found a similar inverse association [11]. In contrast to these studies, other epidemiological studies have found no apparent association between statin use and the risk of RCC or kidney cancer overall [7–9,12], and one study reported an increased risk of kidney and other urologic cancers associated with statin use [13]. The Danish health system offers unique opportunities to study associations between drug use and cancer risk in large population-based cohorts. "
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    ABSTRACT: Background: Use of statins has been suggested to protect against renal cell carcinoma (RCC); however, studies have typically been underpowered, and the results are conflicting. Objective: To determine whether the use of statins is associated with a reduced risk of RCC using high-quality registry data. Design, setting, and participants: We conducted a nationwide case-control study based on all histologically verified cases of RCC in Denmark between 2002 and 2012 (n=4606) matched 1:10 to cancer-free controls. Data on drug use, comorbidity, and educational level were obtained from Danish nationwide prescription, patient, and demographic registries. Outcome measurements and statistical analysis: Odds ratios (ORs) and 95% confidence intervals (CIs) for RCC associated with long-term use (≥5 yr) of statins were estimated using conditional logistic regression, adjusting for potential confounders. Results and limitations: The adjusted OR for RCC associated with long-term use of statins was 1.06 (95% CI, 0.91-1.23). Analyses stratified by duration of statin use, type of statin, and patient characteristics all yielded ORs close to unity, except for a slightly increased OR for RCC associated with long-term statin use among women (OR: 1.25; 95% CI, 0.96-1.62). The main limitation of our study was lack of information on lifestyle factors, notably obesity, which may have biased the risk estimates upward. Conclusions: Our study does not support an important chemopreventive effect of long-term statin use against RCC. The marginally increased and statistically insignificant risk estimates can readily be interpreted as a null finding, considering the lack of control for obesity and other lifestyle risk factors. Patient summary: Previous studies have shown that the use of cholesterol-lowering drugs (statins) may protect against renal cancer. In a large study including all Danish renal cancers during an 11-yr period, we found no evidence of such an effect.
    European Urology 10/2015; DOI:10.1016/j.eururo.2015.10.020 · 13.94 Impact Factor
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    • "Secondary analyses of randomised clinical trials of statin use and coronary heart disease have not had adequate statistical precision to evaluate comprehensively the association between statin use and ovarian cancer risk (Dale et al, 2006), and only four observational studies have specifically reported on the risk for ovarian cancer associated with statin use (Kaye and Jick, 2004; Friedman et al, 2008; Yu et al, 2009; Lavie et al, 2013). This prompted us to examine the association between statin use and ovarian cancer risk in a large nationwide case–control study. "
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    ABSTRACT: Background: Limited data suggest that statin use reduces the risk for ovarian cancer. Methods: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer overall, and for histological types, associated with statin use. Results: We observed a neutral association between ever use of statins and epithelial ovarian cancer risk (OR=0.98, 95% CI=0.87-1.10), and no apparent risk variation according to duration, intensity or type of statin use. Decreased ORs associated with statin use were seen for mucinous ovarian cancer (ever statin use: OR=0.63, 95% CI=0.39-1.00). Conclusions: Statin use was not associated with overall risk for epithelial ovarian cancer. The inverse association between statin use and mucinous tumours merits further investigation.
    British Journal of Cancer 11/2014; 112(1). DOI:10.1038/bjc.2014.574 · 4.84 Impact Factor
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    • "A total of 1,139,584 subjects, including 15,297 haematological malignancies cases were involved. Of the 20 included studies, eight studies were conducted in Europe [20], [25], [27], [29], [33]–[36], nine studies in America [21]–[23], [26], [28], [31], [32], [38], [39], and remaining three studies in other countries [24], [30], [37]. Nine studies were hospital-based [21], [22], [24], [34]–[39], and 11 studies were population-based [20], [23], [25]–[33]. "
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    ABSTRACT: Several observational studies have shown that statin use may modify the risk of haematological malignancies. To quantify the association between statin use and risk for haematological malignancies, we performed a detailed meta-analysis of published studies regarding this subject. We conducted a systematic search of multiple databases including PubMed, Embase, and Cochrane Library Central database up to July 2013. Fixed-effect and random-effect models were used to estimate summary relative risks (RR) and the corresponding 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression. Subgroup analyses and sensitivity analysis were also performed. A total of 20 eligible studies (ten case-control studies, four cohort studies, and six RCTs) reporting 1,139,584 subjects and 15,297 haematological malignancies cases were included. Meta-analysis showed that statin use was associated with a statistically significant 19% reduction in haematological malignancies incidence (RR = 0.81, 95% CI [0.70, 0.92]). During subgroup analyses, statin use was associated with a significantly reduced risk of haematological malignancies among observational studies (RR = 0.79, 95% CI [0.67, 0.93]), but not among RCTs (RR = 0.92, 95% CI [0.77, 1.09]). Based on this comprehensive meta-analysis, statin use may have chemopreventive effects against haematological malignancies. More studies, especially definitive, randomized chemoprevention trials are needed to confirm this association.
    PLoS ONE 01/2014; 9(1):e87019. DOI:10.1371/journal.pone.0087019 · 3.23 Impact Factor
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