Esophageal cancer (EC) is the eighth-most-common cancer worldwide, with two common sub-types — squamous cell carcinoma (SCC) and adenocarcinoma (AC). Several risk factors have been associated with this cancer, including smoking, alcohol consumption, gastroesophageal reflux disease (GERD) and Barrett’s esophagus (Table 1). Many studies have implicated diet and nutrition in risk of these cancers. However, dietary behaviors are complex and certain dietary habits can be correlated with other health behaviors as well as demographic factors, hence definitive conclusions are challenging. Here, we attempt to review the literature about dietary components that have been associated with either increased or decreased risk of esophageal cancer.
Table 1: Substances that demonstrate reduction of dysplasia or precancerous lesions, with specific risk factors
|GERD||Vitamins A, C and E|
|Barrett’s esophagus||Fiber, dark-green vegetables, beta-carotene, vitamins A, C and E|
Most reports demonstrating any associations are retrospective, with very few prospective studies. In addition, there are limited data regarding the exact quantities consumed to achieve these associations. Studies on single foods and nutrients found to have a beneficial effect include non-starchy vegetables, fruits, and foods containing beta-carotene and vitamin C. Other findings demonstrate a positive association between esophageal cancer and milk, soups, red meat, and butter, and an inverse relationship with white meat, fish, raw vegetables and fruits. These findings are summarized in Table 2.
Table 2: Food and Nutrient Associations with Esophageal Carcinoma
|Increased Risk||Decreased Risk||No Risk Association|
|Squamous Cell Carcinoma||↓ Folate
↑ Red meat: ↓ Poultry
↑ Red and processed meats in men
↑ Maté consumption
Green tea - in females
|Adenocarcinoma||↑ Meats (especially processed meats)
High dairy fat
|Regular raw fruit and vegetables intake
↑ Vitamin B6 consumption
Green tea and coffee
Polyunsaturated fats if BMI normal
Red meat has demonstrated a positive association with EC in multiple studies. Methods of cooking at high temperature, as well as the heme iron present in red meat, are thought to contribute to the risk. The latter contributes to endogenous formation of N-nitroso compounds. White meat has a much lower association with esophageal cancers, likely due to the lower heme iron content. An increased red-meat-to-poultry ratio has been correlated with an increased risk of SCC.
Processed meat intake is probably associated with total EC risk. These foods are rich in N-Nitroso compounds, and cooking can also lead to the generation of heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH), thus increasing the potential of mutagenesis.
There are limited studies investigating the relationship between esophageal cancer and components of meat or compounds formed during cooking or processing of meat. It has been hypothesized that mutagenic HCAs and PAHs generated from cooking meats at high temperature methods, such as pan frying or grilling over an open flame, could contribute to EC risk.
Fish consumption as a risk factor in esophageal carcinogenesis remains poorly studied. Studies have suggested it plays little or no direct role in risk reduction. However, incorporation of fish and other lean meats may suggest decreased consumption of red and preserved meats, leading to a perceived protective effect.
Fruit and vegetable content in diet has been suggested to be inversely associated with risk of esophageal cancer. The protective effects are thought to be mediated by fiber, lutein and folate. The association appears to be stronger for adenocarcinomas than for squamous cell carcinomas. Other studies have demonstrated a fruit-and-vegetable-rich diet was associated with a significant decrease in SCC.
Dietary fiber has several anticarcinogenic effects and is thought to be protective against esophageal cancer. Dietary fiber is thought to reduce carcinogenesis by modulating gastroesophageal reflux and aiding with weight control.
Teas have been thought to demonstrate a protective effect, as their components often exhibit antioxidative, anti-inflammatory, antimicrobial and immunostimulant effects in vitro. Tea administration could inhibit the N-nitroso-compound-induced esophageal tumorigenesis.
Coffee contains numerous anticarcinogenic components. Caffeine suppresses cyclin-dependent kinase-4-induced cell growth. Other components, cafestol and kahweol, could inhibit DNA damage. These theories still warrant further elucidation. Maté is a tea-like infusion made from the leaves of the perennial tree common in South American countries. A meta-analysis demonstrated an increased risk of cancer with maté. There were multiple confounders, but the role in pathogenesis was attributed to thermal injury, as the association was not seen with cold beverages containing maté. Consumption of green tea, as well as coffee, has demonstrated a protective effect on EC; however, black tea consumption has no association with any kind of EC.
Micro- and Macro-nutrients
Folate is a water-soluble B vitamin occurring naturally in dark-green, leafy vegetables, legumes and citrus fruits. It is significantly associated with a reduced risk of EC. Folate deficiency is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol consumption.
N-nitroso compounds are believed to act as pro-oxidants and catalyze lipid peroxidation resulting in DNA damage in tissues. Processed foods and metabolism of heme iron are potential sources of N-nitroso compounds.
Dietary fat intake has been reported to have an association with EC risk, although results have been inconsistent. One prospective study found no associations between dietary fat intake and EC. The study did, however, find a protective effect of polyunsaturated fat intake in subjects with a normal BMI in AC. Another study showed that diets high in dairy fat were associated with an increased meat-and-fat pattern that increased the risk of AC.
Carbohydrates have been studied with respect to their glycemic load (GL) and glycemic index (GI) and have a possible positive association with EC and SCC, in particular. It is postulated that diets with a high GI contain rapidly absorbable carbohydrates that result in high blood glucose levels and consequently increased insulin demand. This inadvertently increased Insulin Like Growth Factor 1 (IGF1), which has been associated with potentiating several cancers.
While single foods have demonstrated either a protective effect or increased risk, diets are more complex and encompass many of the previously noted food groups. It may be more beneficial to study whole diets to learn what role diet can play in reduction of risk for esophageal SCC or AC. A few studies have already demonstrated a reduced risk of cancer in those who follow Mediterranean diets as well as diets based on the Healthy Eating Index (HEI) and Dietary Guidelines for Americans Adherence Index (DGAI) 2005. However, more prospective studies are needed.
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