The increasing incidence of esophageal adenocarcinoma over the course of the past 30 years has provoked scientific and epidemiologic interest. Most relevant, nutrition-based research to date consists of case-controlled studies. Nonetheless, certain dietary associations with the disease have emerged (Fig. 3). Obesity and a high fat diet have been seen to increase the risk of esopha-geal cancer, whereas several nutrients appear to reduce its incidence. These are discussed individually.
Obesity is an established risk factor for both esophageal and gastric cardial adenocarcinoma, the association with the former being stronger. Obesity's etiological role in esophageal adenocarcinoma, in contrast to squamous cell carcinoma, was established in 1995 (73,74). An American study subsequently demonstrated a fourfold increased risk of esophageal adenocarcinoma in those in the highest quartile of body mass index (BMI) compared with the lowest quartile (75). Even more dramatic results published an eightfold increased risk for individuals in the highest quartile compared with the lowest BMI, along with a 16-fold increase between obese subjects (BMI > 30) and those with BMI <22 (level 1b evidence) (76).
A fairly bold statement is that "oesophageal adenocarcinoma is a largely preventable disease in women" (77). Nonetheless, having identified 74 affected women in the United Kingdom, Cheng et al. identified high BMI at the age of 20 years to be a significant risk factor for the condition. Having highlighted the incidence of esophageal adenocarcinoma in British women amongst the highest incidence in the country, they summarized that obesity and low fruit consumption had a population attributable risk of 90%.
The multifactorial nature of esophageal adenocarcinoma, probably involving both host and genetic factors, was highlighted in a recent review (78). It is logical to suppose that the strikingly
increased risk of esophageal adenocarcinoma with both GERD and obesity may be attributed to the independent association of these two etiological factors with each other. This failed to be confirmed in one large case-controlled study from Sweden (79), thereby raising the possibility that hormonal effects may underlie the association of obesity and esophageal cancer.
Diets high in total fat, saturated fat, and cholesterol are associated with an increased risk of esophageal adenocarcinoma. The largest, population-based, case-control study was undertaken in the United States, and demonstrated that dietary fat was significantly associated with adenocarcinoma, although not squamous-cell carcinoma, of the esophagus (80).
The role of alcohol in esophageal carcinogenesis, specifically in the development of adenocarci-noma, remains somewhat controversial. It has been suggested that the main risk factors for the development of cancers of the oral cavity, pharynx, and esophagus in the developed world are tobacco and alcohol, together accounting for 75% of these cancers (81). The mechanism by which alcohol has this effect is not clear, although it is likely to be a direct effect on the endothelium (82).
A further study found a statistically significant increased risk of esophageal adenocarci-noma in smokers and a strong association of alcohol with squamous-cell carcinoma of the esophagus (83). However, neither beer nor liquor drinking was shown to be significantly associated with adenocarcinoma of the esophagus, and wine drinking was associated with a significant decrease in risk.
A meta-analysis of 14 studies conducted between 1966 and 2001 found the carcinogenic effects of alcohol and tobacco to be multiplicative on the relative-risk scale of cancers of the upper aerodigestive tract (84). Contrary to the conclusion of the aforementioned study, this meta-analysis also isolated alcohol as an independent risk factor for esophageal adenocarcinoma.
Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several carcinomas, including esophageal and gastric. It is believed that the vitamins and minerals in these foods may contribute to the reduced cancer risk.
A scientific review of 206 epidemiologic and 22 animal studies looked at the association of various cancers with fruit and vegetable consumption (85). Along with several other cancer sites, there appeared to be an evidence for the protective effect of these foods in esophageal cancer. The most protective effect seemed to be from raw vegetables, followed by allium vegetables, carrots, green vegetables, cruciferous vegetables, and tomatoes. The protective substances appeared to include dithiolthiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflaveanes, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, vitamin C, D-limonene, lutein, folic acid, beta carotene, lycopene, selenium , vitamin E, flava-noids, and dietary fiber.
One particular study observed that the dietary nutrients most beneficial in the prevention of esophageal adenocarcinoma are the antioxidants, principally vitamin C, beta-carotene, and vitamin E (86). In support of this finding is a scientific study that isolated lower levels of vitamin C in the plasma and mucosa of patients with BE compared with those with squamous mucosa (87). This would be consistent with the suggested role of oxidative stress in the patho-genesis and neoplastic progression of BE.
Interestingly, one of the case-controlled studies discussed earlier suggested a distinction between plant- and animal-derived nutrients (80). They concluded that nutrients associated with a lower risk of esophageal adenocarcinoma were predominantly derived from plant-based foods, whereas those derived from animal origin appeared to result in an increased risk. They also concluded that, of all the nutrients studied, dietary fiber had the greatest effect on risk reduction.
Whether micronutrient supplementation would influence cancer risk and mortality was investigated in a local community in China (88). The region studied has one of the highest esophageal and gastric cardia cancer rates in the world. Although the results were not definitive, the study of 29,584 adults did suggest that vitamin and mineral supplementation reduces esophageal cancer risk (level 1b evidence). The particular combination of beta carotene, vitamin E, and selenium was found to be most beneficial.
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