Principal Component Analysis of Dietary and Lifestyle Patterns in Relation to Risk of Subtypes of Esophageal and Gastric Cancer
Introduction
An increasing incidence of adenocarcinomas of the esophagus (EA) and the gastric cardia (GCA), though to a lesser extent, has been well noted in the literature, with incidence rising over six-fold between 1973 and 2002 1, 2, 3. The increasing trends are persisting in the United States (4) and have been found in Great Britain, Australia, The Netherlands, Denmark, and other western nations (5). In response to the rising trend, the study described herein was initiated in the United States to investigate potential risk factors. This, and other studies have thus far shown that obesity 6, 7, 8, 9, tobacco use 10, 11, 12, 13, and gastroesophageal reflux disease (GERD) 14, 15, 16 are important risk factors for EA and GCA, and that Helicobacter pylori colonization 17, 18, 19 may be an important protective factor.
It has been theorized that fruits and vegetables, which are high in antioxidants, phytosterols, and other substances, may inhibit carcinogenesis by free-radical quenching or by blocking the formation of N-nitroso compounds 20, 21, 22. Although epidemiologic studies have found that fruits and vegetables are associated with a decreased risk of gastric and esophageal cancers without regard to subsite or histologic type 23, 24, evidence linking dietary factors to subtypes of these cancers is more limited. In earlier reports of the present multicenter, population-based study, we found significant inverse associations between intake of nutrients found primarily in plant-based foods and the risk of EA and GCA 25, 26. In another U.S. population-based study, Brown et al. (6) observed a significantly reduced risk of EA among white men reporting the highest intake of raw fruits, raw vegetables, and cruciferous vegetables. Although they did not find a consistent association between consumption of meat, poultry, and fish and risk of EA (6), we observed a significant positive association between intake of meat and animal protein and risk of EA and GCA 25, 26. We and others have also presented evidence of an inverse association between dietary fiber intake and risk of EA 6, 25 and GCA 25, 27. For non-cardia gastric adenocarcinoma (OGA), the available evidence suggests a positive association with nitrite-containing foods in western countries and salted or preserved foods in Asian countries (24).
Analyses of independent effects of individual dietary items are complicated by the correlations in consumption of foods in the typical diet within and between food groups. For example, intakes of fruits and vegetables are associated positively and negatively with consumption of other food groups (28). Also, patterns of dietary intake are correlated with other factors known to affect health such as smoking and socioeconomic status 29, 30, 31, 32. Thus, studies that focus on individual nutrients or food groups may overlook these correlations as well as potential interactions among differing foods or food groups. Alternative analyses of diet and lifestyle patterns have therefore begun to be explored to try to help explain the role of diet in chronic disease etiology 33, 34, 35. Principal components analysis (PCA) makes it possible to identify potentially interpretable patterns in the data by weighting variables within a principal component. The resulting weighted linear combinations of variables in a principal component identify variables that co-vary and lend themselves to interpretations and assignments of titles that have common sense meanings. The use of an analysis of this nature allows for the capture of variation in overall food intake among the study subjects in a nicely interpretable manner. Four such analyses have examined esophageal 36, 37 and gastric cancer 36, 37, 38, 39 outcomes. The findings of these studies are discussed in detail, in light of our results, in the discussion section.
The analyses presented herein supplement our previous nutrient and food group analyses 25, 26 based on more traditional epidemiologic methods of dietary assessment/analysis by using PCA to examine patterns of these same dietary factors along with other established risk factors for these cancers (e.g., BMI, GERD, smoking).
Section snippets
Study Population
The methods of subject recruitment and data collection have been described in detail previously (12). A multicenter, population-based, case-control study of adenocarcinoma of the esophagus, squamous cell carcinoma of the esophagus (ESCC), adenocarcinoma of the gastric cardia, and adenocarcinoma of other anatomic sites of the stomach was conducted in three geographic areas of the United States with population-based tumor registries: the entire state of Connecticut, a 15-county area of New
Results
Principal component loadings for each of the variables of interest based on data from the controls are shown in Table 1. Six patterns were retained in the analysis, which accounted for 48% of the total variance. The first pattern loaded heavily on nitrite, high-nitrite meats, and red meats, and was therefore termed a Meat/Nitrite pattern. In addition, high-fat dairy, vitamin C, refined grains, fiber, poultry, and starchy vegetables also loaded with this pattern. In contrast, the second
Discussion
In this relatively large population-based case-control study of men and women in the United States, we identified six dietary/lifestyle patterns, which subsequently were shown to tend to discriminate cases from controls. The meat/nitrite principal component was consistently positively associated with each of the four cancers of interest, with the strongest association seen for EA. Significant positive associations were also found between the GERD/BMI pattern and EA risk, and between the
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