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. 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. 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. 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.

We conducted a systematic meta‐analysis of observational studies on cigarette smoking and cancer from 1961 to 2003. The aim was to quantify the risk for 13 cancer sites, recognized to be related to tobacco smoking by the International Agency for Research on Cancer (IARC), and to analyze the risk variation for each site in a systematic manner. We extracted data from 254 reports published between 1961 and 2003 (177 case‐control studies, 75 cohorts and 2 nested case‐control studies) included in the 2004 IARC Monograph on Tobacco Smoke and Involuntary Smoking. The analyses were carried out on 216 studies with reported estimates for ‘current’ and/or ‘former’ smokers. We performed sensitivity analysis, and looked for publication and other types of bias. Lung (RR = 8.96; 95% CI: 6.73–12.11), laryngeal (RR = 6.98; 95% CI: 3.14–15.52) and pharyngeal (RR = 6.76; 95% CI: 2.86–15.98) cancers presented the highest relative risks (RRs) for current smokers, followed by upper digestive tract (RR = 3.57; 95% CI: 2.63–4.84) and oral (RR = 3.43; 95% CI: 2.37–4.94) cancers. As expected, pooled RRs for respiratory cancers were greater than the pooled estimates for other sites. The analysis of heterogeneity showed that study type, gender and adjustment for confounding factors significantly influence the RRs estimates and the reliability of the studies.

ContextColorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. The association between cigarette smoking and colorectal cancer has been inconsistent among studies.ObjectiveTo clarify the association of cigarette smoking and colorectal cancer, we performed a comprehensive literature search and a meta-analysis of observational studies considering both incidence and mortality.Data SourcesWe performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE to May 2008, with no restrictions. We also reviewed references from all retrieved articles.Study SelectionAll articles that were independent and contained the minimum information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty.Data ExtractionArticles were reviewed and data were extracted and cross-checked independently by 3 investigators, and any disagreement was resolved by consensus among all 3.ResultsOne hundred six observational studies were included in the analysis of incidence. Twenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [CI], 1.11-1.25). Smoking was associated with an absolute risk increase of 10.8 cases per 100 000 person-years (95% CI, 7.9-13.6). We found a statistically significant dose-relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever vs never smokers was 1.25 (95% CI, 1.14-1.37). Smoking was associated with an absolute risk increase of 6.0 deaths per 100 000 person-years (95% CI, 4.2-7.6). For both incidence and mortality, the association was stronger for cancer of the rectum than of the colon.ConclusionCigarette smoking is significantly associated with colorectal cancer incidence and mortality.

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). 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. 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. Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.

Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodellingin vivoand reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer. These findings reveal unanticipated communication between stress-induced neural signalling and inflammation, which regulates tumour lymphatic architecture and lymphogenous tumour cell dissemination. These findings suggest that limiting the effects of SNS signalling to prevent tumour cell dissemination through lymphatic routes may provide a strategy to improve cancer outcomes.