Tobacco and alcohol are well established risk factors for esophageal SCC, increasing risk by 3 to 8 and 3 to 5-fold, respectively. In contrast, alcohol consumption appears to be a weak risk factor for EAC with some studies reporting no positive correlation. Recent reports also indicate that total alcohol is not a strong risk for BE and that an inverse association may exist for BE among wine drinkers.
Smoking increases EAC risk the range of 1.5 to 4-fold. Interestingly, although the magnitude of risk associated with AEC and tobacco use is lower compared to SCC, the duration of risk reportedly remains elevated for 30 years after tobacco cessation, thus providing a logical window for chemopreventive interventions.
A number of case control, cohort, and intervention studies have examined the role of dietary factors, dietary patterns and supplement intake related to esophageal cancer risk. In summary, diets rich in fruits and vegetables have consistently been associated with reduced risk, whereas those of animal origin characterized by high meat intake and saturated fat consumption generally increase risk.
In addition, recent research investigated a number of dietary factors in BE patients including the “Western” dietary pattern (high in fast food and meat) compared to the “health conscious” (high in fruit, vegetables, and non-fried fish). Their findings reported that a health conscious dietary pattern was inversely associated with BE and that a diet of fast food and meat may adversely impact BE.
Another investigation of BE patients utilizing a case-control study design reported that dietary antioxidants, fruits, and vegetables were inversely associated with BE; however, the group found no modification of risk for BE with supplement intake. In contrast, a prospective study conducted by the Seattle Barrett’s Esophagus Program revealed that BE patients who took one or more multivitamins per day had a significantly decreased risk of EAC and tetrapoidy compared to patients not taking vitamins.
The authors reported current NSAID use, high consumption of fruits and vegetables, and low fat intake to be associated with lower incidence of EAC and fewer alterations in ploidy, a marker of neoplastic progression. Intake of supplemental vitamin C, E, B-carotene and selenium were associated with reduced risk for EAC and ploidy. The different results of these studies may be attributed to a number of factors. The case control study focused on BE risk, whereas the prospective study evaluated risk of progression to EAC suggesting that the protective impact of supplemental vitamins may be specific to a later phase of neoplastic progression or that the differences are due to other factors.
Divergent study methods or true differences in the population cohorts themselves may have resulted in the reported outcomes. An earlier chemopreventive intervention focused on patients at increased risk for esophageal SCC found that the long-term response to supplementation may be age dependent as well.
The intervention trial was conducted in an area of high esophageal cancer rates in an undernourished population in China reported that the long-term impact of vitamin and mineral supplementation depended on the age of the population. Those 55 years of age and younger benefited, while those over 55 years of age actually experienced increased risk for esophageal SCC.
The baseline nutritional status of the population, as well as risk behaviors and age of the population, may be important considerations for conducting interventions aimed at decreasing esophageal cancer risk. Another recent investigation evaluated diet, multivitamin use, and gene promoter methylation among smokers reported that multivitamin intake, consumption of green, leafy vegetables and folate significantly protected against altered methylation of cancer-related genes.
A significant amount of work remains with regard to our knowledge of how, when, and where to intervene in specific high risk patients cohorts for improved patient outcomes, namely cancer prevention. Still, the body of research continues to support an inverse association between BE, EAC and high levels of fruit and vegetable consumption which in turn has led to a number of preclinical evaluations as well as early phase clinical trials evaluating food-based chemopreventives, including berries.
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