Matteo Rota

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.

European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women?

BACKGROUND Cancer mortality statistics for 2015 were projected from the most recent available data for the European Union (EU) and its six more populous countries. Prostate cancer was analysed in detail. PATIENTS AND METHODS Population and death certification data from stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organisation database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected 2015 numbers of deaths by age group were obtained by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS A total of 1,359,100 cancer deaths are predicted in the EU in 2015 (766,200 men and 592,900 women), corresponding to standardised death rates of 138.4/100,000 men and 83.9/100,000 women, falling 7.5% and 6%, respectively, since 2009. In men, predicted rates for the three major cancers (lung, colorectum and prostate) are lower than in 2009, falling 9%, 5% and 12%. Prostate cancer showed predicted falls of 14%, 17% and 9% in the 35-64, 65-74 and 75+ age groups. In women, breast and colorectal cancers had favourable trends (-10% and -8%), but predicted lung cancer rates rise 9% to 14.24/100,000 becoming the cancer with the highest rate, reaching and possibly overtaking breast cancer rates--though the total number of deaths remain higher for breast (90 800) than lung (87 500). Pancreatic cancer has a negative outlook in both sexes, rising 4% in men and 5% in women between 2009 and 2015. CONCLUSIONS Cancer mortality predictions for 2015 confirm the overall favourable cancer mortality trend in the EU, translating to an overall 26% fall in men since its peak in 1988, and 21% in women, and the avoidance of over 325,000 deaths in 2015 compared with the peak rate.

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.

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.

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.

Random-effects meta-regression models for studying nonlinear dose-response relationship, with an application to alcohol and esophageal squamous cell carcinoma

A fundamental challenge in meta-analyses of published epidemiological dose-response data is the estimate of the function describing how the risk of disease varies across different levels of a given exposure. Issues in trend estimate include within studies variability, between studies heterogeneity, and nonlinear trend components. We present a method, based on a two-step process, that addresses simultaneously these issues. First, two-term fractional polynomial models are fitted within each study included in the meta-analysis, taking into account the correlation between the reported estimates for different exposure levels. Second, the pooled dose-response relationship is estimated considering the between studies heterogeneity, using a bivariate random-effects model. This method is illustrated by a meta-analysis aimed to estimate the shape of the dose-response curve between alcohol consumption and esophageal squamous cell carcinoma (SCC). Overall, 14 case-control studies and one cohort study, including 3000 cases of esophageal SCC, were included. The meta-analysis provided evidence that ethanol intake was related to esophageal SCC risk in a nonlinear fashion. High levels of alcohol consumption resulted in a substantial risk of esophageal SCC as compared to nondrinkers. However, a statistically significant excess risk for moderate and intermediate doses of alcohol was also observed, with no evidence of a threshold effect.

The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks

CONTEXT Tobacco smoke includes a mix of carcinogens implicated in the etiology of bladder cancer (BC) and renal cell cancer (RCC). OBJECTIVE We reviewed the impact of tobacco exposure on BCC and RCC incidence and mortality, and whether smoking cessation decreases the risk. EVIDENCE ACQUISITION A systematic review of original articles in English was performed in August 2013. Meta-analysis of risks was performed using adjusted risk ratios where available. Publication bias was assessed using Begg and Egger tests. EVIDENCE SYNTHESIS We identified 2683 papers, of which 107 fulfilled our inclusion criteria, of which 83 studies investigated BC and 24 investigated RCC. The pooled relative risk (RR) of BC incidence was 2.58 (95% confidence interval [CI] 2.37-2.80) for all smokers, 3.47 (3.07-3.91) for current smokers, and 2.04 (1.85-2.25) for former smokers. The corresponding pooled RR of BC disease-specific mortality (DSM) was 1.47 (1.24-1.75), 1.53 (1.12-2.09) and 1.44 (0.99-2.11). The pooled RR of RCC incidence was 1.31 (1.22-1.40) for all smokers, 1.36 (1.19-1.56) for current smokers, and 1.16 (1.08-1.25) for former smokers. The corresponding RCC DSM risk was 1.23 (1.08-1.40), 1.37 (1.19-1.59), and 1.02 (0.90-1.15). CONCLUSIONS We present an up-to-date review of tobacco smoking and BC and RCC incidence and mortality. Tobacco smoking significantly increases the risk of BC and RCC incidence. BC incidence and DSM risk are greatest in current smokers and lowest in former smokers, indicating that smoking cessation confers benefit. We found that secondhand smoke exposure is associated with a significant increase in BC risk. PATIENT SUMMARY Tobacco smoking affects the development and progression of bladder cancer and renal cell cancer. Smoking cessation reduces the risks of developing and dying from these common cancers. We quantify these risks using the most up-to-date results published in the literature.