Cigarette Smoking Increases Risk of Barrett's Esophagus: An Analysis of the Barrett's and Esophageal Adenocarcinoma Consortium

Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett’s esophagus (BE). We investigated whether tobacco smoking and other factors increase risk for BE

Quantitative real-time RT-PCR validation of differential mRNA expression of SPARC, FADD, Fascin, COL7A1, CK4, TGM3, ECM1, PPL and EVPL in esophageal squamous cell carcinoma

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors and typically presents at an advanced and rapidly fatal stage. To better understand the role of genetics in the etiology and prevention of ESCC and to identify potential susceptibility genes as well as early detection markers, we previously compared tumor and matched normal tissues from ESCC patients from a high-risk area of China using cDNA expression microarrays and identified 41 differentially-expressed genes (13 over-expressed and 28 under-expressed). METHODS: In the current study, we validated and quantitated differential mRNA expression in a sample of nine of these 41 genes, including four that were over-expressed (SPARC, FADD, Fascin, COL7A1), and five that were under-expressed (CK4, TGM3, ECM1, PPL, EVPL), in 75 new ESCC patients using quantitative Real-time RT-PCR and the 2(-ΔΔCT )method to examine both tumor and matched normal tissue. In addition, we examined expression patterns for these genes by selected demographic and clinical characteristics. RESULTS: Four previously over-expressed (tumor ≥2-fold normal) genes were all increased in the majority of new ESCC patients: SPARC was increased in 71% of patients, Fascin in 70%, FADD in 63%, and COL7A1 in 57%. Five previously under-expressed (tumor ≤0.5-fold normal) genes similarly showed decreased mRNA expression in two-thirds or more of patients: CK4 was decreased in 83% of patients, TGM3 in 77%, ECM1 in 73%, and PPL and EVPL in 67% each. In subset analyses, associations with age (for COL7A1), family history (for PPL and ECM1), and alcohol use (for SPARC and Fascin) were also noted. CONCLUSION: These data indicate that these nine genes have consistent differential mRNA expression, validating results of our previous cDNA array results, and affirming their potential role in the early detection of ESCC

Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

<p>Abstract</p> <p>Background</p> <p>Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse.</p> <p>Methods</p> <p>600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated.</p> <p>Results</p> <p>Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29).</p> <p>Conclusion</p> <p>These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.</p

Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) 1-3 of esophageal squamous cell carcinoma (ESCC) in ethnic Chinese (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study, and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% CI 0.82-0.88; P=7.72x10−20) and rs1642764 at 17p13.1 (per-allele OR= 0.88, 95% CI 0.85-0.91; P=3.10x10−13). rs7447927 is a synonymous single nucleotide polymorphism (SNP) in TMEM173 and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR=1.33, 95% CI 1.22-1.46; P=1.99x10−10). Our joint analysis identified new ESCC susceptibility loci overall as well as a new locus unique to the ESCC high risk Taihang Mountain region

Physicians and smoking cessation. A survey of office procedures and practices in the Community Intervention Trial for Smoking Cessation

OBJECTIVE: To obtain a baseline measure of tobacco control activities carried out by physicians and of tobacco control policies and practices in physician offices. DESIGN: All primary care physicians in 11 communities were asked through a mail survey about their tobacco control practices. Thirty offices in each community were randomly selected and interviewed by telephone to determine office policies and practices. SETTING: Both surveys assessed primary care settings in the 11 intervention communities. RESULTS: The physicians\u27 survey (response rate, 48%) indicated that physicians report intervention with smokers more than 70% of the time, but the interventions rarely include key behavioral elements necessary for smoking modification. Physicians who received formal training in smoking cessation reported that they believed themselves to be more prepared and that they spent more time counseling patients than physicians who were not trained. The office survey (response rate, 83.2%) indicated that smoke-free policies are in place in most clinics and offices and that many offices provide printed materials on smoking cessation. However, few offices had staff to coordinate smoking cessation activities. These surveys will be repeated following the intervention phase of the Community Intervention Trial for Smoking Cessation to assess changes in counseling practices and office policies. CONCLUSION: There is a positive relationship between attending training and intervening with more cessation activities. Physicians perceive themselves as prepared to help smokers, but few are providing more than advice to stop smoking

Tobacco control activities of primary-care physicians in the Community Intervention Trial for Smoking Cessation. COMMIT Research Group

OBJECTIVE: To compare tobacco control practices of physicians and their staff in Intervention communities with those in Comparison communities of the Community Intervention Trial for Smoking Cessation (COMMIT). DESIGN: COMMIT was a randomised trial testing community-based intervention for smoking cessation carried out over four years. SETTING: Eleven matched pairs of communities assigned randomly to Intervention and Comparison conditions. PARTICIPANTS AND INTERVENTIONS: Physicians in the Intervention communities participated in continuing medical education (CME). Training for office staff focused on tobacco control and office intervention systems . OUTCOME MEASURES: Smoking control attitudes and practices reported by primary-care physicians in the 22 communities, smoking policies, and practices of 30 randomly selected medical offices in each community, and patient reports of physician intervention activities. RESULTS: Response rates to the physicians\u27 mail survey were 45% and 42% in Intervention and Comparison communities, respectively. Telephone interviews of office staff had response rates of 84% in both conditions. Physicians in Intervention communities were more likely to attend training than those in Comparison communities (53% and 26%, respectively (PCONCLUSIONS: The COMMIT intervention had a significant effect on some reported physician behaviours, office practices, and policies. However, most physicians still did not use state-of-the-art smoking intervention practices with their patients and there was little, or no, difference between patient reports of intervention activities of physicians in the Intervention and Comparison communities. Better systems and incentives are needed to attract physicians and their staff to CME and to encourage them to follow through on what they learn. The recently released Agency for Health Care Policy and Research clinical practice guideline for smoking cessation and other standards and policies outline these systems and offer suggestions for incentives to facilitate adoption of these practices by physicians