Lorenza Scotti

Alcohol drinking and colorectal cancer risk: an overall and dose–response meta-analysis of published studies

BACKGROUND The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (≤1 drink/day) and moderate (2-3 drinks/day) alcohol drinking, investigation of the dose-response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region. METHODS Twenty-seven cohort and 34 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects meta-regression models were used for modeling the dose-risk relation. RESULTS The RRs were 1.21 [95% confidence interval (CI) 1.13-1.28] for moderate and 1.52 (95% CI 1.27-1.81) for heavy (≥4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13-1.37) than for women (RR = 1.08, 95% CI 1.03-1.13; P(heterogeneity) = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33-2.46; P(heterogeneity) = 0.04). The dose-risk analysis estimated RRs of 1.07 (95% CI 1.04-1.10), 1.38 (95% CI 1.28-1.50), and 1.82 (95% CI 1.41-2.35) for 10, 50, and 100 g/day of alcohol, respectively. CONCLUSIONS This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk.

Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis

Background:Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.Methods:We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose–response meta-regression models and investigated potential sources of heterogeneity.Results:A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose–risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin’s and Non-Hodgkin’s lymphomas were inversely associated.Conclusions:Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.

Cancer Risk Associated with Use of Metformin and Sulfonylurea in Type 2 Diabetes: A Meta-Analysis

OBJECTIVE Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue. MATERIALS AND METHODS We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancer sites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ(2) statistics and measured with the I(2) statistic. Publication bias was evaluated using funnel plot and Eggers regression asymmetry test. RESULTS Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metformin was associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54-0.70), colorectal cancer (0.64, 95% CI 0.54-0.76), and pancreatic cancer (0.38, 95% CI 0.14-0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site. CONCLUSIONS Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.

A meta-analysis on alcohol drinking and gastric cancer risk

BACKGROUND Whether an association between alcohol drinking and gastric cancer risk exists is an open question. In order to provide a definite quantification of the association between alcohol drinking and gastric cancer risk, we conducted a meta-analysis of available data. PATIENTS AND METHODS We carried out a PubMed search of articles published up to June 2010 and identified 44 case-control and 15 cohort studies, including a total of 34 557 gastric cancer cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. We carried out a dose-risk analysis using nonlinear random-effects meta-regression models. RESULTS Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers = 1.17, 95% CI 0.78-1.75) than for gastric cardia (RR = 0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day. CONCLUSIONS This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking.BACKGROUND Whether an association between alcohol drinking and gastric cancer risk exists is an open question. In order to provide a definite quantification of the association between alcohol drinking and gastric cancer risk, we conducted a meta-analysis of available data. PATIENTS AND METHODS We carried out a PubMed search of articles published up to June 2010 and identified 44 case-control and 15 cohort studies, including a total of 34 557 gastric cancer cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. We carried out a dose-risk analysis using nonlinear random-effects meta-regression models. RESULTS Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (≥4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers=1.17, 95% CI 0.78-1.75) than for gastric cardia (RR=0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day. CONCLUSIONS This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking.

Does drinking pattern modify the effect of alcohol on the risk of coronary heart disease? Evidence from a meta-analysis

Objective: To evaluate the strength of the evidence provided by epidemiological literature investigating drinking pattern as effect modifier of alcohol intake on the risk of coronary heart disease (CHD). Design: Meta-analysis of observational studies. Data sources: Medline, citation tracking, from 1966 to 2006. Review methods: Original studies investigating the amount of alcohol intake, combined with the frequency of alcohol consumption and/or pattern of alcohol drinking affecting the risk of CHD were extracted. Among them, cohort and case–control studies reporting sufficient data to perform statistical analyses and using people who abstained from alcohol as the reference were included. Results: Six (4 cohort and 2 case–control) out of 118 studies reviewed met the inclusion criteria. Compared with those who abstained from alcohol, regular heavy drinkers and heavy irregular or binge drinkers showed significantly different pooled relative risks of 0.75 (95% confidence interval 0.64 to 0.89) and 1.10 (1.03 to 1.17) respectively. The dose–response relation between the amount of alcohol intake and CHD risk was significantly different in regular and irregular drinkers. A J-shaped curve, with nadir around 28 grams of alcohol per week, and last protective dose of 131 grams per week, was obtained including drinkers who consumed alcohol for 2 days a week or less. Conversely, in people who consumed alcohol for more than 2 days a week a significant protective effect was seen even when drinking high amounts of alcohol. Conclusion: This meta-analysis suggests that binge and heavy irregular drinking modify the favourable effect of alcohol intake on the CHD risk. However, this conclusion should be taken with caution because of the small number of studies considered.

Alcohol drinking and pancreatic cancer risk: a meta-analysis of the dose-risk relation

In order to provide a more precise quantification of the association between alcohol consumption and pancreatic cancer risk, we performed a meta‐analysis of relevant dose‐risk results. We conducted a PubMed search of all case‐control (N=21) and cohort (N=11) studies published up to March 2009. We computed summary relative risk (RR) estimates using either fixed‐ or, in the presence of heterogeneity, random‐effects models. The pooled RR was 0.92 (95% confidence interval, 95% CI, 0.86–0.97) for <3 drinks/day and 1.22 (95% CI, 1.12–1.34) for ≥3 drinks/day. The increased risk for heavy drinking was similar in women and men, but apparently stronger in cohort studies (RR=1.29), in studies with high quality index (RR=1.30), and did not appear to be explained by residual confounding by either history of pancreatitis or tobacco smoking. This meta‐analysis provides strong evidence for the absence of a role of moderate drinking in pancreatic carcinogenesis, coupled to an increased risk for heavy alcohol drinking. Given the moderate increase in risk and the low prevalence of heavy drinkers in most populations, alcohol appears to be responsible only for a small fraction of all pancreatic cancers.

Alcohol drinking and esophageal squamous cell carcinoma with focus on light-drinkers and never-smokers - A systematic review and meta-analysis

Quantification of the association between alcohol drinking and risk of esophageal squamous cell carcinoma (ESCC) is an open issue, particularly among light alcohol drinkers, never‐smokers, and Asian populations, in which some high‐risk polymorphisms in alcohol metabolizing genes are more prevalent. To address these issues, we conducted a systematic review and meta‐analysis using 40 case‐control and 13 cohort studies that reported on the risk associated with alcohol drinking for at least three levels of consumption. In studies adjusted for age, sex, and tobacco smoking, the relative risk (RR) and 95% confidence interval (CI) for the association between light alcohol drinking (≤12.5 g/d) and risk of ESCC was 1.38 (1.14–1.67). The association was slightly stronger in Asian countries than in other populations. The adjusted RRs (95% CIs) were 2.62 (2.07–3.31) for moderate drinking (>12.5–<50 g/d) and 5.54 (3.92–7.28) for high alcohol intake (≥50 g/d); the RRs were slightly higher in non‐Asian populations. In prospective studies, the RR (95% CI) was 1.35 (0.92–1.98) for light, 2.15 (1.55–2.98) for moderate, and 3.35 (2.06–5.46) for high alcohol intakes; light drinking showed an association with ESCC in Asia (five studies) but not in other regions (three studies). Among never‐smokers (nine studies), the RR (95% CI) was 0.74 (0.47–1.16) for light, 1.54 (1.09–2.17) for moderate, and 3.09 (1.75–5.46) for high intakes. This meta‐analysis further corroborates the association of moderate and high alcohol intake with risk of ESCC and provides risk estimates based on multiple prospective studies. Light alcohol intake appears to be associated to ESCC mainly in studies in Asia, which suggests a possible role of genetic susceptibility factors.

A meta-analysis of alcohol drinking and oral and pharyngeal cancers. Part 1: Overall results and dose-risk relation

Alcohol consumption, together with tobacco, is the best recognised risk factor for oral and pharyngeal cancers (OPC), but several important aspects of this association need to be further explored. In order to provide up to date and more precise quantification of the association between alcohol drinking and OPC risk, we conducted a meta-analysis of available data. We performed a PubMed search of articles published up to September 2009, and we identified 43 case-control and two cohort studies presenting results for at least three categories of alcohol drinking, including a total of 17,085 OPC cases. We derived meta-analytic summary estimates using random-effects models, and taking into account correlation between estimates. We also performed a dose-risk analysis using non-linear random-effects meta-regression models. The pooled relative risk (RR) was 1.21 (95% confidence interval, CI, 1.10-1.33) for <or=1 drink per day, and rose to 5.24 (95% CI, 4.36-6.30) for heavy alcohol drinking (>or=4 drinks per day). The dose-risk analysis resulted in RR of 1.29 for 10g ethanol/day, 3.24 for 50g ethanol/day, 8.61 for 100g ethanol/day, and 13.02 for 125g ethanol/day. This meta-analysis provides more precise evidence of a gross excess of OPC risk for heavy alcohol drinkers. It also indicates an increased risk for moderate doses, i.e., <or=1 drink or 10g ethanol/day.

Stroke risk and NSAIDs: a systematic review of observational studies

To perform a quantitative systematic review of observational studies on the risk of stroke associated with the use of individual NSAIDs.

Alcohol drinking and laryngeal cancer: Overall and dose-risk relation - A systematic review and meta-analysis

Alcohol drinking is a known risk factor for laryngeal cancer. However, little information is available on the risk associated with light alcohol drinking. To address this issue, we conducted a meta-analysis using two methods: (i) random-effects models with reconstruction of alcohol consumption categories and calculation of risk estimates associated with predefined consumption levels using Hamling method and (ii) random-effects meta-regression models. The PubMed database was searched for all case-control or cohort studies published in the English language on the association between alcohol consumption and risk of laryngeal cancer. Forty studies (38 case-control, 2 cohort) reporting on at least three levels of consumption were included. Overall, alcohol drinking versus non-drinking was associated with an approximately 2-fold increase in risk of laryngeal cancer (RR=1.90; 95% CI: 1.59-2.28). While light alcohol drinking (≥1 drink/day) did not show any significant association with risk of laryngeal cancer (12 studies. RR=0.88; 95% CI: 0.71-1.08), moderate drinking (>1 to <4drinks/day) was associated with a 1.5-fold increase in risk (35 studies. RR=1.47; 95% CI: 1.25-1.72) and heavy drinking (⩾4drinks/day) was associated with a 2.5-fold increased risk (33 studies. RR=2.62; 95% CI: 2.13-3.23). Subgroup analyses for studies that adjusted for main potential confounding factors (age, sex, and tobacco use) and several further subgroup analyses showed similar results, which suggest the robustness of the results.