Independent associations between low-density lipoprotein cholesterol and cancer among patients with type 2 diabetes mellitus

Background

The risk association between low-density lipoprotein (LDL) cholesterol and cancer remains controversial and largely unexplored for people not receiving statin therapy.

Methods

We examined the risk association between LDL cholesterol and cancer among patients with type 2 diabetes mellitus who were free of cancer at enrolment and whose statin use was known. We considered a variety of nonlinear relationships in our analysis.

Results

During a median follow-up period of 4.90 years, cancer developed in 270 (4.4%) of 6107 patients. Among the 3800 patients who did not receive statin therapy, the risk association between LDL cholesterol and cancer was represented by a V-shaped curve. Compared with patients whose LDL cholesterol was at least 2.80 mmol/L but less than 3.80 mmol/L, the risk of cancer, death from any cause or the composite outcome of cancer or death was greater among those with an LDL cholesterol level of less than 2.80 mmol/L (hazard ratio for cancer 1.74, 95% confidence interval [CI] 1.20–2.52) and those with an LDL cholesterol level of 3.80 mmol/L or greater (hazard ratio for cancer 1.87, 95% CI 1.29–2.71). Using 3.8 mmol/L as a reference point, we found that the hazard ratio for cancer for every millimole per litre absolute change in LDL cholesterol was 1.54 (95% CI 1.19–1.99) among patients not using statins; the hazard ratio was reduced to 1.24 (1.01–1.53) for the entire sample (statin users and those not using statins). These associations persisted after adjustment for covariates and exclusion of patients with less than 2.5 years of follow-up.

Interpretation

Among patients with type 2 diabetes, the association between LDL cholesterol and cancer was V-shaped, whereby both low and high levels of LDL cholesterol were associated with elevated risk of cancer.Emerging data suggest an association between diabetes mellitus and an increased risk of cancer,¹ including breast cancer in women;² colorectal,³ pancreatic^4,5 and liver⁶ cancer in both men and women; and prostate cancer in men.⁷ Several prospective analyses, including the US National Health and Nutrition Examination Survey,⁸ have demonstrated an inverse relation between serum total cholesterol and cancer incidence and mortality in the general population, although few studies have investigated this relation among patients with type 2 diabetes mellitus. In 2004, the US National Cholesterol Education Program Adult Treatment Panel III recommended treatment targets for low-density lipoprotein (LDL) cholesterol of less than 1.81 mmol/L (less than 70 mg/dL) for patients with very high risk of coronary artery disease and less than 2.59 mmol/L (less than 100 mg/dL) for patients with high risk of coronary artery disease;⁹ these targets were intended for both diabetic and nondiabetic patients.These recommendations remain controversial. Although one recent analysis of a large cohort of patients treated with statins showed a greater risk of cancer with achievement of low LDL cholesterol,¹⁰ a more recent study reported otherwise.¹¹ Furthermore, the independent associations between LDL cholesterol level and cancer in both the general population and in patients with type 2 diabetes have not been explored. We conducted a hypothesis-generating study to explore the possible independent association between LDL cholesterol and cancer risk in Chinese patients with type 2 diabetes mellitus.     

Colorectal cancer risk and dyslipidemia: A case–cohort study nested in an Italian multicentre cohort

BackgroundDyslipidemia is an established risk factor for many diseases, but its effect on colorectal cancer risk is less clear. We investigated the association of colorectal cancer risk with plasma triglycerides, total, HDL, and LDL cholesterol in four Italian EPIC centers.MethodsWe conducted a case–cohort study on participants recruited to four Italian EPIC centers (Turin, Varese, Naples, and Ragusa; 34,148 subjects). A random subcohort of 850 subjects was obtained and 286 colorectal cancer cases were diagnosed. Triglycerides, total and HDL cholesterol were determined in plasma samples obtained at baseline and stored at −196 °C; LDL cholesterol was calculated. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Cox regression models using the Prentice method.ResultsThe highest tertiles of total (HR 1.66, 95%CI 1.12–2.45) and LDL cholesterol (HR 1.87, 95%CI 1.27–2.76) were associated with increased colorectal cancer risk compared to lowest tertiles. Risks were greater for men than women, and for postmenopausal than premenopausal women. Highest tertiles of total and LDL cholesterol were also significantly associated with increased risks of colon cancer, distal colon cancer, and rectal cancer, but not proximal colon cancer.ConclusionsOur findings suggest that high levels of total and LDL cholesterol increase colorectal cancer risk, particularly in men and postmenopausal women. However additional studies are needed to clarify the role of plasma lipids in these cancers, particularly in view of the conflicting findings of previous studies.     

Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti-Diabetic Therapy: A Nationwide,Population-Based Cohort Study

BackgroundThe relationship between diabetes mellitus (DM) and cancer incidence has been evaluated in limited kinds of cancer. The effect of anti-diabetic therapy (ADT) on carcinogenesis among diabetic patients is also unclear.ResultsIncidence of cancer at any site was significantly higher in patients with DM than in those without (p<0.001). The risk of carcinogenesis imparted by DM was greatest in gastroenterological malignancies (liver, pancreas, and colorectal cancer) as well as lung, breast and oral cancer (p<0.001). Among the oral types of ADT, metformin decreased the risk of lung and liver cancer, but had less effect on reducing the risk of colorectal cancer. α-glucosidase inhibitor decreased the risk of developing liver, colorectal, and breast cancer. Apart from intermediate-acting insulin, rapid-acting, long-acting, and combination insulin treatment significantly reduced the overall cancer risk among all DM patients. In subgroup analysis, long-acting insulin treatment significantly decreased the risk of lung, liver, and colorectal cancer.ConclusionOur results supported the notion that pre-existing DM increases the incidence of gastroenterological cancer. ADT, especially metformin, α-glucosidase inhibitor, and long-acting insulin treatment, may protect patients with DM against these malignancies. It is crucial that oncologists should closely collaborate with endocrinologists to provide an optimal cancer-specific therapy and diabetic treatment to patients simultaneously with cancer and DM.     

HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm,Sweden: A registry-based cohort study

BackgroundThe relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality.Methods and findingsThis cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins.In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%).A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens.ConclusionsStatin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

In this cohort study, Rita Bergqvist and colleagues investigate the relationship between statin treatment and COVID-19 mortality.     

Lack of effect of lowering LDL cholesterol on cancer: meta-analysis of individual data from 175,000 people in 27 randomised trials of statin therapy

Background

Statin therapy reduces the risk of occlusive vascular events, but uncertainty remains about potential effects on cancer. We sought to provide a detailed assessment of any effects on cancer of lowering LDL cholesterol (LDL-C) with a statin using individual patient records from 175,000 patients in 27 large-scale statin trials.

Methods and Findings

Individual records of 134,537 participants in 22 randomised trials of statin versus control (median duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration 5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738 [1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]). Moreover, there was no evidence of any effect of reducing LDL-C with statin therapy on cancer incidence or mortality at any of 23 individual categories of sites, with increasing years of treatment, for any individual statin, or in any given subgroup. In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10]).

Conclusions

In 27 randomised trials, a median of five years of statin therapy had no effect on the incidence of, or mortality from, any type of cancer (or the aggregate of all cancer).     

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

BackgroundVitamin D deficiency is repeatedly reported in colorectal cancer (CRC). Since cholesterol and vitamin D share common precursor 7-dehydrocholesterol (7-DHC), it would be important to explore the associations of key vitamin D metabolites and serum lipid parameters in patients with high and low grade CRC. The aim of this study was to analyze relationships between serum 25(OH)D3, 24,25(OH)2D3 and 7-DHC levels and serum lipids in patients with CRC, and to evaluate their potential for prediction of risk for development of high grade CRC.MethodsWe recruited 82 patients CRC and 77 controls. 7-DHC, 25(OH)D3 and 24,25(OH)2D3 were quantified by LC-MS/MS methods.Results7-DHC, 25(OH)D3 and vitamin D metabolic ratio (VDMR) were significantly lower in CRC patients than in control group (P<0.001, P<0.010, P<0.050 and P<0.050, respectively). 25(OH)D3 levels were higher in patients with grade I CRC when compared to grade II (P<0.050). All vitamin D metabolites positively correlated with total cholesterol (TC) concentration in CRC patients. 25(OH)D3 was significant predictor of increased CRC risk (P<0.010). After adjustment for TC concentration, 25(OH)D3 lost its predictive abilities. However, 25(OH)D3 remained significant predictor of poorly differentiated type of cancer (P<0.050).ConclusionsWe found significant positive association between vitamin D status and serum total cholesterol. Although low 25(OH)D3 was found to be a significant risk factor for CRC development, the obtained results primarily suggest profound impact of cholesterol level on vitamin D status in CRC. However, our results suggest that low 25(OH)D3 might independently contribute to development of poorly differentiated tumor.     

Variations in prostate biopsy recommendation and acceptance confound evaluation of risk factors for prostate cancer: Examining race and BMI

BackgroundProstate cancer is ubiquitous in older men; differential screening patterns and variations in biopsy recommendations and acceptance will affect which man is diagnosed and, therefore, evaluation of cancer risk factors. We describe a statistical method to reduce prostate cancer detection bias among African American (n = 3398) and Non-Hispanic White men (n = 22,673) who participated in the Selenium and Vitamin E Cancer Prevention trial (SELECT) and revisit a previously reported association between race, obesity and prostate cancer risk.MethodsFor men with screening values suggesting prostate cancer but in whom biopsy was not performed, the Prostate Cancer Prevention Trial Risk Calculator was used to estimate probability of prostate cancer. Associations of body mass index (BMI) and race with incident prostate cancer were compared for observed versus imputation-enhanced outcomes using incident density ratios.ResultsAccounting for differential biopsy assessment, the previously reported positive linear trend between BMI and prostate cancer in African American men was not observed; no BMI association was found among Non-Hispanic White men.ConclusionsDifferential disease classification among men who may be recommended to undergo and then consider whether to accept a prostate biopsy leads to inaccurate identification of prostate cancer risk factors. Imputing a man’s prostate cancer status reduces detection bias. Covariate adjustment does not address the problem of outcome misclassification. Cohorts evaluating incident prostate cancer should collect longitudinal screening and biopsy data to adjust for this potential bias.     

Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study

Background

Statins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.

Methods

A case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n?=?325). Patients diagnosed with diabetes mellitus type II (DM II n?=?65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a ‘recent’ statin user or not at the time of diagnosis.

Results

Statin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6–29.0%, p?=?0.601). When comparing groups 20–64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0–26.6%, p?=?0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing ‘former/never’ statin users as reference category with ‘recent’ users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89–2.16).

Conclusions

No significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between ‘recent’ statin use at the time of diagnosis and cancer-specific survival.

     

结直肠癌患者血清GDF-15、G-CSF水平与临床病理特征及预后的关系

摘要 目的：探究结直肠癌血清生长分化因子-15（GDF-15）、粒细胞集落刺激因子（G-CSF）水平与患者临床病理参数、预后的关系,并分析其对结直肠癌的诊断价值。方法：采集结直肠癌患者、结直肠腺瘤患者及健康体检志愿者的血清样本,酶联免疫吸附测定（ELISA）实验检测血清GDF-15、G-CSF;分析结直肠癌患者血清GDF-15、G-CSF水平与患者临床病理参数的关系;Kaplan Meier生存曲线分析血清GDF-15、G-CSF水平与患者预后的关系;受试者工作特征曲线（ROC）分析血清GDF-15、G-CSF水平对结直肠癌的诊断价值。结果：结直肠癌患者血清GDF-15、G-CSF水平高于结直肠腺瘤患者及健康体检志愿者（均P<0.05）;血清GDF-15水平与肿瘤直径、分化程度、远处转移及TNM分期相关（均P<0.05）;血清G-CSF水平与肿瘤分化程度、远处转移及TNM分期相关（均P<0.05）;Kaplan Meier生存曲线结果显示,血清GDF-15低表达、G-CSF低表达患者的术后5年总生存率及中位生存时间均分别高于血清GDF-15高表达、G-CSF高表达患者（均P<0.05）;ROC分析结果表明,血清GDF-15、G-CSF有较好的诊断结直肠癌的价值,血清GDF-15、G-CSF联合应用的敏感度、特异度分别为0.876、0.863。结论：结直肠癌患者血清GDF-15、G-CSF水平升高,且均与患者病情恶性进展、不良预后相关;血清GDF-15、G-CSF是诊断结直肠癌的潜在指标。     

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis

BackgroundThe aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association.MethodsA cohort of 8391 patients with newly diagnosed Dukes’ A-C CRC (2009–2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality.ResultsIn the Scottish cohort, statin use before diagnosis (HR = 0.84, 95% CI 0.75–0.94), but not after (HR = 0.90, 95% CI 0.77–1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I² = 0%,heterogeneity P = 0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n = 86,622, pooled HR = 0.82, 95% CI 0.79–0.86) but this association was less apparent and more heterogeneous (I² = 67%,heterogeneity P = 0.03) with statin use after diagnosis in 4 studies (n = 19,152, pooled HR = 0.84, 95% CI 0.68–1.04).ConclusionIn a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies.     

Association between comorbidity and participation in breast and cervical cancer screening: A systematic review and meta-analysis

BackgroundComorbidity is associated with poor outcomes for cancer patients but it is less clear how it influences cancer prevention and early detection. This review synthesizes evidence from studies that have quantified the association between comorbidity and participation in breast and cervical screening.MethodsPubMed, CINAHL and EMBASE databases were systematically searched using key terms related to cancer screening and comorbidity for original research articles published between 1 January 1991 and 21 March 2016. Two reviewers independently screened 1283 studies that met eligibility criteria related to Population (adult, non-cancer populations), Exposure (comorbidity), Comparison (a ‘no comorbidity’ group), and Outcome (participation in breast cancer or cervical screening). Data was extracted and risk of bias assessed using a standardised tool from the 22 studies identified for inclusion (17 breast; 13 cervical). Meta-analyses were performed for participation in breast and cervical screening, stratified by important study characteristics.ResultsThe majority of studies were conducted in the United States. Results of individual studies were variable. Most had medium to high risk of bias. Based on the three “low risk of bias” studies, mammography screening was less common among those with comorbidity (pooled Odds Ratio 0.66, 95%CI 0.44–0.88). The one “low risk of bias” study of cervical screening reported a negative association between comorbidity and participation.ConclusionWhile a definitive conclusion could not be drawn, the results from high quality studies suggest that women with comorbidity are less likely to participate in breast, and possibly cervical, cancer screening.     

Expression of p27Kip1 and bcl-2, cigarette smoking,and colorectal cancer risk

Although a positive association between cigarette smoking and colorectal adenoma development is consistently found, the association with colorectal cancer remains controversial. We evaluated the potential roles of p27^Kip1 and bcl-2 protein expressions in conjunction with cigarette smoking exposure and colorectal cancer risk in a hospital-based case-control study. A total of 163 colorectal cancer patients from Roswell Park Cancer Institute and Buffalo General Hospital and 326 healthy controls responded to a standardized questionnaire on colorectal cancer risk factors including detailed information on their history of cigarette smoking; 110 of the patients' tumours were available for immunohistochemical analysis of p27^Kip1 and bcl-2 protein overexpression. An avidin-biotin immunoperoxidase procedure was used to determine expression after incubation with mouse monoclonal p27^Kip1 and mouse monoclonal bcl-2 antibodies, respectively. A statistically significant trend for total pack-years of smoking was found when p27^Kip1 positive cases were compared with p27^Kip1 negative cases (trend test, p = 0.007). Although a weak inverse association was observed with smoking exposure among p27^Kip1 negative tumour cases in comparison to controls, a significant dose-response association was seen with p27^Kip1 positive tumours. The relative risk of developing a p27^Kip1 positive tumour was estimated to be 1.17 (95% CI 0.54-2.54) for those with less than 20 pack-years, 1.95 (95 % CI 0.95-3.97) for those with 20-39 pack-years, and 2.25 (95% CI 1.14-4.45) for those with greater than 39 pack-years of smoking exposure (trend test, p = 0.009) when compared with controls. When cases with bcl-2 expression were compared with cases without bcl-2 expression, suggestion of a trend was also observed with pack-years smoked (trend test, p = 0.09). In our study of 110 patients with sporadic colorectal cancer and 326 controls, we observed differences in associations between cigarette smoking and expressions in p27^Kip1 and bcl-2. Our data suggest that bcl-2 overexpression (or a bcl-2 dependent pathway) is associated with cigarette smoking in the development of colorectal cancer, whereas a loss of p27^Kip1 expression is not. These associations indicate that there is aetiological heterogeneity in colorectal cancer development, and that they can indirectly allude to where these changes in protein expression occur in the adenoma-carcinoma sequence (i.e. early versus late events).     

Statin Use and Risk of Lung Cancer: a Meta-Analysis of Observational Studies and Randomized Controlled Trials

Clinical studies have shown that statin use may alter the risk of lung cancer. However, these studies yielded different results. To quantify the association between statin use and risk of lung cancer, we performed a detailed meta-analysis. A literature search was carried out using MEDLINE, EMBASE and COCHRANE database between January 1966 and November 2012. Before meta-analysis, between-study heterogeneity and publication bias were assessed using adequate statistical tests. Fixed-effect and random-effect models were used to calculate the pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses, sensitivity analysis and cumulative meta-analysis were also performed. A total of 20 (five randomized controlled trials, eight cohorts, and seven case–control) studies contributed to the analysis. Pooled results indicated a non-significant decrease of total lung cancer risk among all statin users (RR = 0.89, 95% CI [0.78, 1.02]). Further, long-term statin use did not significantly decrease the risk of total lung cancer (RR = 0.80, 95% CI [0.39 , 1.64]). In our subgroup analyses, the results were not substantially affected by study design, participant ethnicity, or confounder adjustment. Furthermore, sensitivity analysis confirmed the stability of results. The findings of this meta-analysis suggested that there was no significant association between statin use and risk of lung cancer. More studies, especially randomized controlled trials and high quality cohort studies are warranted to confirm this association.     

Lack of an Association between Angiotensin Receptor Blocker Based Therapy and Increased Risk of Cancer: Evidence from Large Observational Studies

Background

A previous meta-analysis of randomized controlled studies that were not designed to investigate cancer as a primary outcome suggested that ARB-based therapy is associated with increased risk of cancer; however, results of recent observational studies considering the association have been contradictory. This study sought to evaluate the association between angiotensin receptor blocker (ARB)-based therapy and risk of cancer by conducting a meta-analysis of observational studies.

Methods

Relevant articles published before February 2014 were identified by searching PubMed and the Cochrane Library. Pooled relative risks (RRs) were determined using a random effects model and were used to assess the strength of association between use of ARB-based therapy and risk of cancer.

Results

Six retrospective cohort studies involving a total of 3,827,109 participants and four case-control studies involving a total of 193,029 cases were included. The present study found that ARB-based therapy was not significantly associated with an increased risk of cancer (RR = 0.87, 95%CI: [0.75, 1.01]). However, an analysis including only cohort studies suggested a significantly decreased risk of cancer among individuals with any history of ARB use as compared to those with no history of ARB use (RR = 0.80, 95%CI: [0.55, 0.95]); no significant association was found between ARB use and risk of cancer when the case-control studies were separately considered (RR = 1.03, 95%CI: [0.93, 1.13]). Subgroup analyses showed that use of ARB-based therapy was associated with decreased risk of lung cancer (RR = 0.81, 95%CI: [0.69, 0.94]); however, no significant associations were found with the other cancer sites investigated. Furthermore, no association was observed upon adjustment by type of ARB drug. No publication bias was detected.

Conclusion

Overall, ARB-based therapy was not associated with increased risk of cancer. However, its use may be related to decreased incidence of lung cancer; this finding should be considered carefully and confirmed with further studies.     

Statins and the Risk of Lung Cancer: A Meta-Analysis

Purpose

Several epidemiologic studies have evaluated the association between statins and lung cancer risk, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. We conducted a meta-analysis of all relevant studies to examine this association.

Methods

A systematic literature search up to March 2012 was performed in PubMed database. Study-specific risk estimates were pooled using a random-effects model.

Results

Nineteen studies (5 RCTs and 14 observational studies) involving 38,013 lung cancer cases contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of lung cancer either among RCTs (relative risk [RR] 0.91, 95% confidence interval [CI] 0.76–1.09), among cohort studies (RR 0.94, 95% CI 0.82–1.07), or among case-control studies (RR 0.82, 95% CI 0.57–1.16). Low evidence of publication bias was found. However, statistically significant heterogeneity was found among cohort studies and among case-control studies. After excluding the studies contributing most to the heterogeneity, summary estimates were essentially unchanged.

Conclusion

The results of our meta-analysis suggest that there is no association between statin use and the risk of lung cancer.     

Association between family history of malignant neoplasm with colorectal adenomatous polyp in 40s aged relative person

PurposeWe assessed the association between a family history of malignancy and risk of colorectal adenoma among individuals aged 40–49 years.MethodsThe study population consisted of subjects, aged in their 40s, who underwent colonoscopy. Their family histories of cancer were collected with a self-administered questionnaire. A logistic regression model was used to assess the association between a family history of cancer and the risk of colorectal polyp.ResultsIn total, 2275 participants were included in the study. Univariate analysis showed that old age, male sex, current cigarette smoking, BMI > 25 kg/m², and a family history of colorectal cancer (CRC) were risk factors for the development of sporadic colorectal adenomatous polyps in these patients. A multivariate analysis showed that a family history of CRC or kidney cancer was associated with adenoma development. A family history of CRC was also a risk factor for advanced and multiple adenoma.ConclusionsThis study shows that a family history of CRC is a risk factor for advanced and multiple colorectal adenoma in people in their 40s. These results support earlier screening for colorectal neoplasms in individuals with a family history of CRC.     

Preoperative statin therapy and infectious complications in cardiac surgery

AimTo assess whether preoperative statin therapy is associated with the risk of postoperative infection in patients undergoing cardiac surgery.Methods520 patients undergoing cardiac surgery in 2010 were retrospectively examined. Data regarding statin and antibiotic use prior to and after surgery were available from the hospital pharmacy information system. Cultures and clinical data of patients on postoperative antibiotics other than standard prophylactic therapy were studied to identify postoperative infections up to 30 days from day of surgery.Results370 (71.2 %) patients were on preoperative statin therapy. Overall, 82 patients (15.8 %) suffered from postoperative infection of which 11 were surgical site infections. In multivariable regression analysis, statin therapy was associated with a reduced risk of postoperative infection (adjusted odds ratio: 0.329, 95 %: CI 0.19–0.57; P < 0.001).ConclusionsPreoperative statin use was associated with a considerable reduced risk of postoperative infections following cardiac surgery. Randomised controlled trials are required to clarify the role of statin therapy in the prevention of postoperative infections.     

Interaction between smoking,GSTM1 deletion and colorectal cancer: results from the GSEC study

Cigarette smoking has inconsistently been associated with an increased risk of colorectal cancer. One of the enzymes responsible for the detoxification of the carcinogenic compounds present in tobacco smoke is glutathione S-transferase-μ (GST-μ). The gene that codes for this enzyme is GSTM1. In this study, we evaluated the associations and interaction between GSTM1 deletion, smoking behaviour and the development of colorectal cancer. We performed a pooled analysis within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). We selected six studies on colorectal cancer, including 1130 cases and 2519 controls, and restricted our analyses to Caucasians because the number of patients from other races was too limited. In addition we performed a meta-analysis including the studies from the GSEC database and other studies identified on MEDLINE on the same subject. The prevalence of the GSTM1 null genotype was within the range reported in other studies: 51.8% of the cases had the GSTM1 null genotype versus 56.6% of the controls. No significant association between the GSTM1 null genotype and colorectal cancer was found (odds ratio 0.92, 95% confidence interval 0.73-1.14). Our results suggest a possible positive association between lack of the GST-μ enzyme and colorectal cancer for non-smoking women (odds ratio 1.47, 95% confidence interval 0.80-2.70). There was no interaction between the effects of smoking and GSTM1 genotype on colorectal cancer risk in men and women (χ²=0.007, p=0.97). Our findings do not support an association between the GSTM1 null genotype and colorectal cancer. In addition, we did not find any modification of the smoking-induced colorectal cancer risk by GSTM1 genotype     

Effect of Statins on Venous Thromboembolic Events: A Meta-analysis of Published and Unpublished Evidence from Randomised Controlled Trials

Background

It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.

Methods and Findings

We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months'' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors'' Summary.

Conclusions

The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out.     

Statin Intolerance: A Review and Update

ObjectiveTo review the evidence of existing literature on the management of statin intolerance.MethodsWe searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022.ResultsStatin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins.ConclusionManagement of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.