The Role of Tobacco, Alcohol, and Obesity in Neoplastic Progression to Esophageal Adenocarcinoma: A Prospective Study of Barrett's Esophagus

Abstract

BackgroundEsophageal adenocarcinoma (EA) incidence in many developed countries has increased dramatically over four decades, while survival remains poor. Persons with Barrett's esophagus (BE), who experience substantially elevated EA risk, are typically followed in surveillance involving periodic endoscopy with biopsies, although few progress to EA. No medical, surgical or lifestyle interventions have been proven to safely lower EA risk.DesignWe investigated whether smoking, obesity or alcohol could predict progression to EA in a prospective cohort of 411 BE patients. Data were collected during personal interview. Adjusted hazard ratios (HR) were estimated using Cox regression.Results39% had body mass index (BMI) over 30 and 64% had smoked cigarettes. Main analyses focused on those with at least 5 months of follow-up (33,635 person-months), in whom 45 developed EA. Risk increased by 3% per year of age (trend p-value 0.02), with approximate doubling of risk among males. EA risk increased with smoking pack-years (trend p-value 0.04) and duration (p-value 0.05). Compared to never-smokers, the HR for those in the highest pack-year tertile was 2.29 (95%CI 1.04–5.07). No association was found with alcohol or BMI, whereas a suggestion of increased risk was observed in those with higher waist-hip ratio, especially among males.ConclusionEA risk significantly increased with increasing age and cigarette exposure. Abdominal obesity, but not BMI, was associated with a modest increased risk. Continued follow-up of this and other cohorts is needed to precisely define these relationships so as to inform risk stratification and preventive interventions.

Abdominal Obesity and Gastroesophageal Cancer Risk: Systematic Review and Meta-Analysis of Prospective Studies

“…Furthermore, six studies [36][37][38][39][40][41] were excluded because the risk estimate for the association of interest was not available. Finally, seven prospective cohort studies [24][25][26][27][28][29] -one publication [28] included two separate cohorts -from six publications were included in the final analysis. The characteristics of the included studies are summarised and listed in Table 1.…”

“…A total of 2130 gastroesophageal cancer cases were diagnosed amongst 913182 participants. Two prospective cohort studies were conducted in the United States [25,26] and Norway [28], and one each in Australia [24], multiple European countries [27], and China [29]. Regarding the sex of the participants, one study [29] evaluated only women and the remaining six [24][25][26][27][28] included both sexes.…”

“…Five prospective cohort studies [24][25][26][27]29] Figure 5). In analysis restricted to studies that adjusted for BMI [25,27,29], higher WHR was positively associated with GC (RR: 1.40, 95% CI: 1.08, 1.82; I 2 =36%, P=0.181), whereas no association was found with esophageal cancer (RR: 2.30, 95% CI: 0.86, 6.17; I 2 =80.5%, P=0.024).…”

“…In addition, intra-abdominal fat has been hypothesised to be biologically different from fat in other areas with regard to tumor angiogenesis and cell proliferation [22,23]. Although general obesity has emerged as a potential risk factor for gastroesophageal cancer, but the association between abdominal obesity and gastroesophageal cancer is still poorly understood, partly because of sparse evidence from prospective studies available at that time, which limited the strength of the conclusions [24][25][26][27][28][29]. Given these considerations, providing clear evidence regarding potentially detrimental effect of abdominal obesity on gastroesophageal cancer would be important for clinical interventions, including weight loss program or weight management program and gastroesophageal cancer screening guidelines for obese individuals.…”

Terrein performs antitumor functions on esophageal cancer cells by inhibiting cell proliferation and synergistic interaction with cisplatin

“…In addition, the mortality rate increased when the esophageal cancer patients were aged 45 years or older (3). Risk factors for esophageal cancer include columnar metaplasia (Barrett's esophagus) (4), obesity (5) and smoking (6,7). A recent study demonstrated that dietary behavior is also associated with esophageal cancer (8).…”