Cigarette smoking and gastric cancer in the stomach cancer pooling (StoP) project

Tobacco smoking is a known cause of gastric cancer, but several aspects of the association remain imprecisely quantified. We examined the relation between cigarette smoking and the risk of gastric cancer using a uniquely large dataset of 23 epidemiological studies within the ‘Stomach cancer Pooling (StoP) Project’, including 10 290 cases and 26 145 controls. We estimated summary odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by pooling study-specific ORs using random-effects models. Compared with never smokers, the ORs were 1.20 (95% CI: 1.09–1.32) for ever, 1.12 (95% CI: 0.99–1.27) for former, and 1.25 (95% CI: 1.11–1.40) for current cigarette smokers. Among current smokers, the risk increased with number of cigarettes per day to reach an OR of 1.32 (95% CI: 1.10–1.58) for smokers of more than 20 cigarettes per day. The risk increased with duration of smoking, to reach an OR of 1.33 (95% CI: 1.14–1.54) for more than 40 years of smoking and decreased with increasing time since stopping cigarette smoking (P for trend<0.01) and became similar to that of never smokers 10 years after stopping. Risks were somewhat higher for cardia than noncardia gastric cancer. Risks were similar when considering only studies with information on Helicobacter pylori infection and comparing all cases to H. pylori+ controls only. This study provides the most precise estimate of the detrimental effect of cigarette smoking on the risk of gastric cancer on the basis of individual data, including the relationship with dose and duration, and the decrease in risk following stopping smoking

Relationship between tobacco, cagA and vacA i1 virulence factors and bacterial load in patients infected by Helicobacter pylori

Background and Aim Several biological and epidemiological studies support a relationship between smoking and Helicobacter pylori (H. pylori) to increase the risk of pathology. However, there have been few studies on the potential synergistic association between specific cagA and vacA virulence factors and smoking in patients infected by Helicobacter pylori. We studied the relationship between smoking and cagA, vacA i1 virulence factors and bacterial load in H. pylori infected patients. Methods Biopsies of the gastric corpus and antrum from 155 consecutive patients in whom there was clinical suspicion of infection by H. pylori were processed. In 106 patients H. pylori infection was detected. Molecular methods were used to quantify the number of microorganisms and presence of cagA and vacA i1 genes. A standardized questionnaire was used to obtain patients’ clinical data and lifestyle variables, including tobacco and alcohol consumption. Adjusted Odds Ratios (ORadjusted) were estimated by unconditional logistic regression. Results cagA was significantly associated with active-smoking at endoscope: ORadjusted 4.52. Evidence of association was found for vacA i1 (ORadjusted 3.15). Bacterial load was higher in active-smokers, although these differences did not yield statistical significance (median of 262.2 versus 79.4 copies of H. pylori per cell). Conclusions The association between smoking and a higher risk of being infected by a virulent bacterial population and with higher bacterial load, support a complex interaction between H. pylori infection and environmental factors

Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the methylation of CpG islands within the DNA and the modification of amino acids in the N-terminal histone tails. In the last years, it became evident that the onset of cancer and its progression may not occur only due to genetic mutations but also because of changes in the patterns of epigenetic modifications. In contrast to genetic mutations, which are almost impossible to reverse, epigenetic changes are potentially reversible. This implies that they are amenable to pharmacological interventions. Therefore, a lot of work in recent years has focussed on the development of small molecule enzyme inhibitors like DNA-methyltransferase inhibitors or inhibitors of histone-modifying enzymes. These may reverse misregulated epigenetic states and be implemented in the treatment of cancer or other diseases, e.g., neurological disorders. Today, several epigenetic drugs are already approved by the FDA and the EMEA for cancer treatment and around ten histone deacetylase (HDAC) inhibitors are in clinical development. This review will give an update on recent clinical trials of the HDAC inhibitors used systemically that were reported in 2009 and 2010 and will present an overview of different biomarkers to monitor the biological effects

Explaining the Chinese Framing of the “Terrorist” Violence in Xinjiang: Insights from Securitization Theory

This paper critically examines the Chinese framing of the “terrorist” violence in Xinjiang. Drawing on the Copenhagen school of securitization theory, it examines how the historical perception of the region as a primary source of security threats to inner China has led today’s China to continue with representing the Han Chinese-Uyghur discord as an existential threat. In framing the ethnic conflict as a security issue, China has capitalized on the global “war on terror” of the early 2000s to transform the unrest into acts of Islamist terrorism to legitimize its counter-insurgency policies in Xinjiang. However, both the 2009 Urumqi riots and the 2014 Kunming attack lead us to conclude that the securitization strategy fails to quell the unrest. Not only have the Strike-Hard campaigns served to radicalize Uyghur nationalists, but also Han Chinese are not convinced that the Chinese government can contain the “terrorist” threat. Yet securitization blinds the leadership to the dysfunctional ethnic policy

Impact of country of birth on genetic testing of metastatic lung adenocarcinomas in France : African women exhibit a mutational spectrum more similar to Asians than to Caucasians

Background: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans. Aim: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform. Patients and Methods: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA. Demographic and clinical features were retrieved from the medical charts. Multivariate binary logistic regression was used to determine the independent predictive factors for the occurrence of specific mutations, in the whole study population or in selected subgroups. Findings: The overall respective incidence of EGFR, KRAS, BRAF, ERBB2 and PI3KCA mutations was 10.5%, 0.9%, 25%, 1.5%, 2.1% and 1.4%, in our study sample including 87.4% white Caucasians, 10.8% Africans and 1.8% Asians; 60.6% men, 30.7% never smoker (median age: 68.3 years). Ethnicity was an independent predictor for EGFR, KRAS and ERBB2 gene abnormalities. In all cases, a significantly higher prevalence of targetable EGFR and ERBB2, and a lower prevalence of resistance KRAS mutations were observed in African women as compared to African men or Caucasians. Conclusions: In real life conditions of routine genetic testing, we have identified subsets of patients with specific targetable activating somatic mutations according to ethnicity, who could preferentially benefit from anti-EGFR and anti-ERBB2 targeted therapies