In this relatively large population-based case-control study of men and women in the U.S. 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 smoking/alcohol pattern and ESCC risk. In contrast, significant inverse associations were found between the fruit/vegetable pattern and risk of both types of esophageal cancer. These findings underscore and build upon our previous reports using these data (7
The elevated risk of EA associated with the meat/nitrite pattern is consistent the findings of Bahmanyar and Ye (37
) who reported a 60% increased risk with a high-meat “Western diet” pattern in an analysis of dietary patterns and EA. In addition, Chen et al. (36
) reported a 3.6-fold elevated risk of EA with a high-meat dietary pattern and Campbell et al. (38
), in an analysis of dietary patterns and gastric adenocarcinomas, reported a statistically significant positive association with a Western dietary pattern among men.
Thus the patterns we observed with the meat/nitrite principal component tend to fit well with previous observations. This principal component loaded high for red meats, high-nitrite meats, and nitrite, but also for high-fat dairy products, poultry, refined grains, dietary fiber, vitamin C, and starchy vegetables, so that inferences cannot be made regarding meats or any specific food product. Also, while the literature generally indicates that fiber is inversely associated with EGA (24
), in our study population, some main sources of fiber were refined grains (white bread, rice, crackers, sugar cereals, pancakes, pizza, and pasta), which are not particularly fiber-rich foods but were consumed in larger quantities than whole grain foods. The case-control difference with respect to this principal component was particularly strong for EA, with a greater than 5-fold increased risk between those with high versus low scoring on the principal component. This principal component may be indicative of a generalized western diet, high in red meats, starchy vegetables and refined grains, of note because EA seems to be a cancer of western nations and not yet increasingly evident in developing or eastern countries.
Our finding that higher fruit/vegetable principal component scores were significantly negatively associated with both subtypes of esophageal cancer adds to the literature showing an inverse association of fruit and vegetable intake with EA and ESCC (6
). Bahmanyar and Ye (37
), in contrast, found no association between their “Healthy Diet” dietary pattern, which was characterized by high fruit, vegetable, fish and poultry consumption, and risk of EA.
In contrast to other investigations (24
), we found no association between the fruit/vegetable principal component and OGA, but a borderline association with GCA. Campbell et al. (38
), in keeping with our finding of a suggested inverse association between the fruit/vegetable principal component and GCA, reported an inverse association between their “Prudent” dietary pattern, which correlated with higher fruit and vegetable consumption, and risk of GCA among both men and women.
In our analyses, the GERD/BMI principal component pattern was associated with a 3.5-fold increased risk of EA. Chronic reflux has emerged along with obesity as an important risk factor for EA (3
). In contrast to the association with EA, the GERD/BMI pattern was significantly inversely associated with ESCC. This case group differed both from controls and the three other case groups in a number of ways, including being significantly leaner and consuming fewer calories per day. At least 3 large studies have found an inverse association between ESCC and BMI (51
). The inverse association between the GERD/BMI pattern and ESCC was stronger prior to adjustment for energy intake (data not shown).
We observed a significant 10-fold increased risk of ESCC in the highest versus lowest quartile of the smoking/alcohol principal component, a finding expected since smoking and drinking are known to be the major risk factors for ESCC (2
). Bahmanyar and Ye (37
) likewise reported a 3.5-fold increased risk of ESCC associated with their “High alcohol” pattern, which was characterized by high beer and liquor intake.
As with case-control studies generally, the present study has several strengths and limitations, including the potential for recall bias. The tumor-type specificity of risks, however, which, for example, included an inverse association between intake of fruits and vegetables and esophageal cancers and GCA, but not OGA, argues against this bias to some extent. We also repeated the PCA on the combined cases and controls and the same components resulted from the analysis, with the exception that the third and fourth components arose in reverse order. That is, the smoking/alcohol PC was third among controls only and fourth among the combined cases and controls. Ultimately, this did not materially alter the results from the logistic regression analysis and therefore, would not change the study conclusions. In addition, due to the high case-fatality rate of these cancers, direct interview data could not be obtained from approximately 30% of cases. When separate analyses excluded proxy interviews, however, the odds ratio estimates remained virtually unchanged.
While our data are consistent with the literature indicating that consuming a diet high in a combination of fruits and vegetables is inversely associated with risk of both subtypes of esophageal cancer and with GCA, they also indicated that smoking and drinking did not load strongly with any diet patterns. It is therefore unlikely that dietary findings, particularly for ESCC, are due to residual confounding, which is often a concern. Also, meat intake did not load strongly with the fruit and vegetable principal component, suggesting that these intakes may have opposing effects on cancer risk. In addition, we found that high-nitrite meat and red meats, loaded together, along with starchy foods, refined grains, and high fat dairy. The resulting principal component, similar to unhealthy “Western” diets reported by other studies (37
) suggests that future analyses of nitrite might need to adjust for non-nitrite rich meats, refined and starchy foods, and possibly high fat dairy products. Further, like our previous reports (7
) these alternative analyses implicate both GERD and obesity as key risk factors for EA. Thus, principal component analysis, which allows for the examination of underlying correlations between variables of interest, particularly dietary and lifestyle components, may yield useful practical conclusions and recommendations for future research, targeted prevention, and framing specific health behavior messages.