Baseline computed tomography screening and blood microRNA predict lung cancer risk and define adequate intervals in the BioMILD trial.

BACKGROUND: Large randomized trials have demonstrated that lung cancer (LC) screening with low-dose computed tomography (LDCT) reduces LC mortality in heavy smokers. We previously showed in the MILD screening trial that the combination of a prespecified circulating microRNA (miRNA) signature classifier (MSC) and LDCT improves the accuracy of LDCT alone. The primary aim of the prospective BioMILD study was to assess the additional value of the blood MSC assay at the time of baseline LDCT with the goal of personalizing LC screening intervals. PATIENTS AND METHODS: The study enrolled 4119 volunteers from January 2013 to March 2016, with a median follow-up of 5.3 years. Baseline LDCT and miRNAs stratified participants into four groups: CT-/MSC- (n = 2664; 64.7%); CT-/MSC+ (n = 800; 19.4%); CT+/MSC- (n = 446; 10.8%); and CT+/MSC+ (n = 209; 5.1%). As per the protocol, those in the CT-/MSC- and CT-/MSC+ groups were allocated to LDCT repeat at 3-year and 1-year intervals; CT+ participants were allocated for 1-year or earlier intervals on the basis of LDCT features independent of MSC results. RESULTS: CT+ participants had a 15.8-fold higher 4-year LC incidence than CT- participants (95% confidence interval 10.34-24.05), and MSC+ participants had a 2.0-fold higher 4-year LC incidence than MSC- participants (95% confidence interval 1.40-2.90); there was no evidence that the MSC effect differed between CT+ and CT- participants. LC incidence at 4 years was 0.8% in CT-/MSC-, 1.1% in CT-/MSC+, 10.8% in CT+/MSC-, and 20.1% in CT+/MSC+ participants. LC mortality rates at 5 years in the four risk groups were 0.5 in CT-/MSC-, 1.5 in CT-/MSC+, 4.2 in CT+/MSC-, and 10.1 in CT+/MSC+. CONCLUSION: The combined use of LDCT and blood miRNAs at baseline predicts individual LC incidence and mortality, with a major effect of MSC for LDCT-positive individuals. These findings may have important implications in personalizing screening intervals.

Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Ten-year results of the Multicentric Italian Lung Detection trial demonstrate the safety and efficacy of biennial lung cancer screening.

BACKGROUND: The Multicentric Italian Lung Detection (MILD) trial demonstrated that prolonged low-dose computed tomography (LDCT) screening could achieve a 39% reduction in lung cancer (LC) mortality. We have here evaluated the long-term results of annual vs. biennial LDCT and the impact of screening intensity on overall and LC-specific mortality at 10 years. PATIENTS AND METHODS: Between 2005 and 2018, the MILD trial prospectively randomised the 2376 screening arm participants to annual (n = 1190) or biennial (n = 1186) LDCT, for a median screening period of 6.2 years and 23,083 person-years of follow-up. The primary outcomes were 10-year overall and LC-specific mortality, and the secondary end-points were the frequency of advanced-stage and interval LCs. RESULTS: The biennial LDCT arm showed a similar overall mortality (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.57-1.12) and LC-specific mortality at 10 years (HR 1.10, 95% CI 0.59-2.05), as compared with the annual LDCT arm. Biennial screening saved 44% of follow-up LDCTs in subjects with negative baseline LDCT, and 38% of LDCTs in all participants, with no increase in the occurrence of stage II-IV or interval LCs. CONCLUSIONS: The MILD trial provides original evidence that prolonged screening beyond five years with biennial LDCT can achieve an LC mortality reduction comparable to annual LDCT, in subjects with a negative baseline examination.

Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy.

BACKGROUND: The National Lung Screening Trial showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduces LC mortality. We evaluated the benefit of prolonged LDCT screening beyond 5 years, and its impact on overall and LC specific mortality at 10 years. DESIGN: The Multicentric Italian Lung Detection (MILD) trial prospectively randomized 4099 participants, to a screening arm (n = 2376), with further randomization to annual (n = 1190) or biennial (n = 1186) LDCT for a median period of 6 years, or control arm (n = 1723) without intervention. Between 2005 and 2018, 39 293 person-years of follow-up were accumulated. The primary outcomes were 10-year overall and LC specific mortality. Landmark analysis was used to test the long-term effect of LC screening, beyond 5 years by exclusion of LCs and deaths that occurred in the first 5 years. RESULTS: The LDCT arm showed a 39% reduced risk of LC mortality at 10 years [hazard ratio (HR) 0.61; 95% confidence interval (CI) 0.39-0.95], compared with control arm, and a 20% reduction of overall mortality (HR 0.80; 95% CI 0.62-1.03). LDCT benefit improved beyond the 5th year of screening, with a 58% reduced risk of LC mortality (HR 0.42; 95% CI 0.22-0.79), and 32% reduction of overall mortality (HR 0.68; 95% CI 0.49-0.94). CONCLUSIONS: The MILD trial provides additional evidence that prolonged screening beyond 5 years can enhance the benefit of early detection and achieve a greater overall and LC mortality reduction compared with NLST trial. CLINICALTRIALS.GOV IDENTIFIER: NCT02837809.

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

UNLABELLED: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. INTRODUCTION: Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. METHODS: We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. RESULTS: In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). CONCLUSION: In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

Screening for gestational diabetes in the Lombardy region: A population-based study.

AIM: As the treatment of hyperglycaemia during pregnancy with diet or insulin reduces the risk of adverse maternal outcomes and perinatal complications, screening for gestational diabetes mellitus (GDM) is included, albeit to variable extents, in all guidelines of care for pregnant women. The aim of the present investigation was to estimate the proportion of pregnancies screened for GDM in Lombardy between 2007 and 2010, and to identify predictors of screening. METHODS: A retrospective cross-sectional study using regional healthcare utilization databases of Lombardy was conducted. The study included all residents of Lombardy without pregestational diabetes who delivered between 1 January 2007 and 31 December 2010. The proportion of pregnancies with at least one screening test for GDM was calculated, along with the odds ratios and 95% confidence intervals associated with selected covariates for GDM screening. RESULTS: Of the 362,818 pregnancies included in the sample, 30% were screened for GDM. The proportion of pregnancies screened increased slightly from 2007 (27%) to 2010 (33%) and with maternal age (from 28% among women<25 years to 32% among those ≥35 years), and varied widely across local health management organizations (HMOs) of residence (range: 20% to 68%). Socioeconomic indicators (education, immigrant status), obstetric history and prepregnancy hypertension were independent predictors of GDM screening. CONCLUSION: The study finding of a low rate of pregnant women screened for GDM among residents of Lombardy supports the need for programmes to improve training of healthcare professionals, to raise women's awareness of GDM and to eliminate barriers to GDM screening.

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.

Alcohol and liver cancer: a systematic review and meta-analysis of prospective studies.

Despite several studies support a positive association between heavy alcohol consumption and liver cancer risk, a consistent dose-risk relationship has not yet been established. We carried out a systematic review and a meta-analysis of the association between alcohol intake and liver cancer occurrence, following the Meta-analysis Of Observational Studies in Epidemiology guidelines. We searched for cohort and nested case-control studies on the general population published before April 2013, using PubMed and EMBASE. Summary meta-analytic relative risks (RRs) were estimated using random-effect models. We included 16 articles (19 cohorts) for a total of 4445 incident cases and 5550 deaths from liver cancer. Compared with non-drinking, the pooled RRs were 0.91 (95% confidence interval, CI, 0.81-1.02) for moderate drinking (< 3 drinks per day) and 1.16 (95% CI, 1.01-1.34) for heavy drinking (≥ 3 drinks per day), with significant heterogeneity among studies. The dose-risk curve suggested a linear relationship with increasing alcohol intake in drinkers, with estimated excess risk of 46% for 50 g of ethanol per day and 66% for 100 g per day. This systematic review suggests a moderate detrimental role of consumption of 3 or more alcoholic drinks per day on liver cancer, and a lack of association with moderate drinking. Our results have to be taken with due caution on account of the possible limitations of the original studies included in the meta-analysis.

Alcohol drinking and cutaneous melanoma risk: a systematic review and dose-risk meta-analysis.

It has been suggested that alcohol intake increases sunburn severity, a major risk factor for cutaneous melanoma (CM). Several epidemiological studies have investigated the relationship between alcohol consumption and CM, but the evidence is inconsistent. Therefore, we aimed to quantify this relationship better, using a meta-analytical approach. The dose-risk relationship was also modelled through a class of flexible nonlinear meta-regression random effects models. The present meta-analysis included 16 studies (14 case-control and two cohort investigations) with a total of 6251 cases of CM. The pooled relative risk (RR) for any alcohol drinking compared with no/occasional drinking was 1·20 [95% confidence interval (CI) 1·06-1·37]. The risk estimate was similar in case-control (RR 1·20, 95% CI 1·01-1·44) and cohort studies (RR 1·26, 95% CI 1·19-1·35). The pooled RR was 1·10 (95% CI 0·96-1·26) for light alcohol drinking (≤ 1 drink per day) and 1·18 (95% CI 1·01-1·40) for moderate-to-heavy drinking. The pooled RR from 10 studies adjusting for sun exposure was 1·15 (95% CI 0·94-1·41), while the RR from six unadjusted studies was 1·27 (95% CI 1·20-1·35). No evidence of publication bias was detected. This meta-analysis of published data reveals that alcohol consumption is positively associated with the risk of CM. However, caution in interpreting these results is required, as residual confounding by sun exposure cannot be ruled out.

Assessing the risk of osteonecrosis of the jaw due to bisphosphonate therapy in the secondary prevention of osteoporotic fractures.

SUMMARY: There is evidence that the use oral bisphosphonates can lead to osteronecrosis of the jaws (ONJ). Although the occurrence of ONJ appears rare among oral bisphosphonates (BPs) users, it is important to know that it exists and can be opportunely minimized. INTRODUCTION: The purpose of this study is to evaluate the association between BPs prescribed for the secondary prevention of osteoporotic fractures and the occurrence of ONJ. METHODS: An Italian record linkage claims database with a target population of around 18 million individuals (6 million over 55 years of age) constituted the data source. We conducted a nested case-control study within a cohort of individuals aged 55+ years old, who were discharged from hospitals with a primary diagnosis of incident osteoporotic fracture. The date related to the discharge diagnosis of ONJ was the index date. Conditional logistic regression for matched data was fitted to estimate the odds ratio (OR) along with 95 % confidence intervals (95 % CI) for the likely association between use of BPs and the risk of ONJ. RESULTS: Any one of the 61 ascertained cases of ONJ (incidence rate, 36.6 per 100,000 person-years) was matched to 20 controls for a total of 1120 controls. When the exposure to BPs was modeled according to recency (i.e., exposure time window prior to the index date) of use, the adjusted OR (95 % CI) for current users was 2.8 (1.3-5.9) against never users. The cumulative use of BPs has shown to increase the incidence of ONJ among patients with primary osteoporotic fractures, although not statistically significant risk has been observed. CONCLUSIONS: Although the risk of BP-related ONJ appears low in non-oncological indications, it is important to be aware that it exists and to know how it may be predicted and possibly minimized.

A meta-analysis of alcohol consumption and the risk of brain tumours.

BACKGROUND: Alcohol is capable of traversing the blood-brain barrier and is thus a possible risk factor for brain cancer. Several epidemiological studies have been published on the issue, a number of those during recent years, with inconsistent findings. MATERIALS AND METHODS: We performed a systematic literature search in the Medline and EMBASE databases. We found a total of 19 studies providing risk estimates for total alcohol or specific alcoholic beverages. Pooled estimates of the relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. RESULTS: The pooled RR of brain cancer for alcohol drinkers versus non-drinkers was 0.97 (95% CI 0.82-1.15; based on 12 studies). Moderate (<2 drinks/day) and heavy alcohol drinkers had RRs of 1.01 (95% CI 0.81-1.25) and 1.35 (95% CI 0.85-2.15), respectively. With reference to specific alcoholic beverages, the RRs were 1.01 (95% CI 0.70-1.48) for wine, 0.96 (95% CI 0.82-1.12) for beer, and 1.20 (95% CI 1.01-1.42) for spirit consumption. The RRs for drinkers versus non-drinkers were 0.93 (95% CI 0.81-1.07) for glioma and 0.71 (95% CI 0.45-1.12) for meningioma. CONCLUSIONS: Alcohol drinking does not appear to be associated with adult brain cancer, though a potential effect of high doses deserves further study.

Light alcohol drinking and cancer: a meta-analysis.

BACKGROUND: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). PATIENTS AND METHODS: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. RESULTS: We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. CONCLUSIONS: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

A meta-analysis of alcohol drinking and oral and pharyngeal cancers: results from subgroup analyses.

AIMS: To quantify the magnitude of the association between alcohol and oral and pharyngeal cancer (OPC) by sex, smoking habits, type of alcoholic beverage and other factors. METHODS: We combined findings from all case-control and cohort studies published until September 2010 and present in this article the results classified by these factors, using a meta-analytic approach. Summary relative risks (RRs) were obtained using random-effects models; heterogeneity was assessed using the χ(2) test. RESULTS: The association between alcohol and OPC risk was similar in men and women, with similar dose-response relationships. No notable differences were found with respect to geographic area and other factors, both for drinking overall and heavy (≥4 drinks/day) drinking. Among never/non-current smokers, the pooled RRs were 1.32 (95% confidence interval, CI, 1.05-1.67) for drinking, and 2.54 (95% CI, 1.80-3.58) for heavy drinking. The corresponding RRs in smokers were 2.92 (95% CI, 2.31-3.70) and 6.32 (95% CI, 5.05-7.90). The pooled RRs for any drinking irrespective of smoking were 2.12 (95% CI, 1.37-3.29) for wine-, 2.43 (95% CI, 1.92-3.07) for beer- and 2.30 (95% CI, 1.78-2.98) for spirits-only drinking. The corresponding RRs for heavy drinking were 4.92 (95% CI, 2.80-8.65), 4.20 (95% CI, 1.43-12.38) and 5.20 (95% CI, 2.77-9.78). CONCLUSION: The alcohol-related RRs are similar with respect to sex, geographic area and type of alcoholic beverage. The association between alcohol and OPC is stronger in smokers than in non-smokers.

Alcohol drinking and risk of renal cell carcinoma: results of a meta-analysis.

BACKGROUND: The role of alcohol consumption in relation with renal cell carcinoma is still unclear; a few studies have reported a beneficial effect of moderate levels of alcohol consumption, whereas it remains still under debate whether there is a dose-response association. MATERIALS AND METHODS: Twenty observational studies (4 cohort, 1 pooled and 15 case-control) reporting results on at least three levels of alcohol consumption were selected through a combined search with PubMed and EMBASE of articles published before November 2010. Overall relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models, and both second-order fractional polynomials and random effect meta-regression models were implemented for the study of dose-risk relation. RESULTS: The estimated RRs were 0.85 (95% CI: 0.80-0.92) for any alcohol drinking, 0.90 (95% CI: 0.83-0.97) for light drinking (0.01-12.49 g/day), 0.79 (95% CI: 0.71-0.88) for moderate drinking (12.5-49.9 g/day) and 0.89 (95% CI: 0.58-1.39) for heavy drinking (≥50 g/day), respectively. CONCLUSION: Our meta-analysis supports the hypothesis of a negative effect of moderate alcohol consumption on the risk of renal cell cancer.

Alcohol drinking and non-Hodgkin lymphoma risk: a systematic review and a meta-analysis.

BACKGROUND: Whether an association between alcohol drinking and non-Hodgkin lymphoma (NHL) risk exists is an open question. In order to provide quantification of the issue, we carried out a meta-analysis of published data. METHODS: We identified 21 case-control and 8 cohort studies, including a total of 18,759 NHL cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. RESULTS: The overall relative risk (RR) of NHL for drinkers versus non-drinkers was 0.85 [95% confidence interval (CI) 0.79-0.91]. Compared with non-drinkers, the pooled RRs were 0.88 for light (≤1 drink per day), 0.87 for moderate (1 to <4 drinks per day), and 0.84 for heavy (≥4 drinks per day) alcohol drinking. There was no association for light drinkers in cohort studies, whereas for moderate and heavy drinkers, the RRs were similar in case-control (0.85 for moderate, 0.92 for heavy) and cohort (0.89 for moderate, 0.79 for heavy) studies. The inverse relation with alcohol consumption (drinkers versus non-drinkers) was similar in men (RR = 0.83) and women (RR = 0.86), but apparently stronger in studies from Asia (RR = 0.69) than other world areas (RR = 0.88). CONCLUSION: This meta-analysis provides quantitative evidence of a favourable role of alcohol drinking on NHL risk, though the lack of a biological explanation suggests caution in the interpretation of results.

Alcohol drinking and bladder cancer risk: a meta-analysis.

BACKGROUND: We aimed at investigating the risk of bladder cancer at different levels of alcohol consumption by conducting a meta-analysis of epidemiological studies. PATIENTS AND METHODS: In October 2010, we carried out a systematic literature search in the Medline database, using PubMed. We identified 16 case-control and 3 cohort studies, including a total of 11 219 cases of bladder cancer, satisfying the inclusion criteria for this meta-analysis. Moderate alcohol intake was defined as <3 drinks per day (i.e. <37.5 g of ethanol per day) and heavy intake as ≥3 drinks/day. Pooled estimates of the relative risks (RR) and the corresponding 95% confidence intervals (CI) were calculated using random effects models. RESULTS: Compared with non-drinkers, the pooled RRs of bladder cancer were 1.00 (95% CI 0.92-1.09) for moderate and 1.02 (95% CI 0.78-1.33) for heavy alcohol drinkers. When we excluded four studies that did not adjust for tobacco smoking, the corresponding estimates were 0.98 (95% CI 0.89-1.07) and 0.97 (95% CI 0.72-1.31). CONCLUSIONS: This meta-analysis of epidemiological studies provides definite evidence on the absence of any material association between alcohol drinking and bladder cancer risk, even at high levels of consumption.

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.