In this hospital-based case-control study, four main dietary patterns were identified, i.e. long-chain SFA (LC-SFA), even-chain unsaturated fatty acid (EC-UFA), short &medium-chain SFA (SMC-SFA), n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) patterns. The EC-UFA pattern was found to be associated with an increased risk of ESCC, whereas the n-3 LC-PUFA pattern was associated with a decreased risk. There was no significant association with the LC-SFA, SMC-SFA patterns observed in the study subjects, however.
Fatty acid is the main structural component of dietary fat. Different types and contents of FAPs have different effects on the occurrence and development of ESCC. Although nutrition has consistently been found to be an important determinant of the ESCC risk, the impact of fatty acid intakes in the etiology of ESCC has not been thoroughly investigated, especially in high-risk countries. Besides, only a few previous studies have evaluated the cumulative effect of fatty acids intakes on the ESCC risk using factor analysis (principal component)[20, 21], while factor analysis as a posteriori method allows the study of synergy among nutrients and consequence of the interactions between them.To our knowledge, there has been no attempt to assess the effect of dietary FAPs on ESCC risk, but some components in the dietary patterns of this study were similar to those of the patterns defined in some other studies, although not all components were identical. The “LC-SFA pattern” “SMC-SFA pattern”, and “n-3 LC-PUFA pattern”, were similar to the FAPs from Korea , Uppsala .
The “LC SFA pattern” and “SMC-SFA pattern” in this study—which was characterized by a high intake of SFA—were no significantly associated with the risk of ESCC. SFAs are major sources of energy, attenuate weight gain, and have strong antibacterial effects, but there is a lack of evidence for the effect of SFA on ESCC risk. In a case-control study with adults in Iran, higher levels of SFA were associated with a lower risk of ESCC. However, In a study in Korea, the “short & medium-chain SFA pattern” was associated with an increased risk of hyper-LDL cholesterolemia in men . Another study highlighted that Saturated fat intake was associated with higher cancer mortality (highest vs. lowest quintile [Q5 vs. Q1]: HR: 1.26, 95% CI 1.20–1.32) in a prospective cohort study of 521,120 participants, with 16 years of follow-up. High intake of saturated fat (but not total, monounsaturated or polyunsaturated fat intake) was associated with increased risk of breast cancer (Q5 vs. Q1: HR 1.13, 95% CI 1.00–1.27) in a large European multicentre prospective study (519,978 participants). Then in this study, SMC-SFA and LC-SFA patterns were not found to be associated with ESCC risk.
Nevertheless, those adhering more to the “even-chain UFA pattern” were found to be at a higher risk of ESCC. The “even-chain UFA pattern” had a high factor loading of even-chain UFA such as DHA(C22:6), nervonic acid(C24:1), EPA(C20:5), eicosenoic acid(C20:1), eicosatrienoic acid(C20:3), AA(C20:4). Some studies have shown that dietary unsaturated fatty acids are associated with an increased risk of cancer. Especially, AA in the even chain fatty acid pattern is a precursor to pro-inflammatory molecules. In humans, the even-chain UFA was found to be correlated with composite inflammation measures and may thus influence the risk of cancer. Inflammation is a crux of the development of many chronic diseases, including cancer. An inflammatory microenvironment is an important part of the tumor microenvironment. Chronic inflammation is the cause of tumor transformation. More studies are essential for exploring their association.
The last pattern of n-3 LC-PUFA was characterized by higher intake of DPA(22:5), docosatrienoic acid(22:3). Many previous studies have proved that the n-3 series of unsaturated fatty acids are mainly derived from fish, and our study also found a positive correlation between the fourth FAP and the intake of deep-sea fish. N-3 LC-PUFA pattern, an important fatty acid that may play a role in preventing some cancers. Furthermore, the n-3 LC-PUFA pattern, which has pleiotropic effects and enhances cancer cell apoptosis, modulates various eicosanoid pathways leading to reduced inflammation, such as suppressing cyclooxygenase-2 synthesis and the inhibition of arachidonic acid-derived eicosanoids. Animal studies and human observational studies have demonstrated that the n-3 LC-PUFA pattern may reduce the risk of cancers such as breast, colon, and prostate[37–39]. In this study, the n-3 LC-PUFA pattern was also found to reduce the risk of ESCC.
When exploring the linear relationship between dietary fatty acid patterns and the risk of ESCC. As we can be seen from Fig. 2, with the increase of EC-UFAs intake, the risk of ESCC increases. However, as the intake of n-3 LC-PUFAs improved, the risk of ESCC decreased. They were associated with a dose-response risk of ESCC. N-3 polyunsaturated fatty acids (PUFAs) express anti-inflammatory properties and prevent tumor progression, which is similar to our result.
Stratified by demographic characteristics and life exposure factors, we found the association between dietary fatty acid pattern and ESCC risk could be modified by smoking, drinking, pickled food, hard food, and fried food. Pickled food is often preserved with the addition of nitrates or nitrites, which increases the formation of N-nitroso compounds (NOCs), which were considered to be animal carcinogens and possible human carcinogens. In addition, high concentrations of salt may increase ESCC risk. Salt might directly damage the esophageal mucosa, leading to susceptibility to esophagitis and an increased risk of ESCC. In this study, there was heterogeneity in the relationship between dietary FAP and the risk of ESCC with the use of preserved foods, and the protective effect of the n-3 LC-PUFA pattern was reduced with the use of preserved foods.
There have been reports that a significant dose-response relationship between the intake frequency of fried food and the risk of ESCC. Cooking meat at high temperatures produces large amounts of polycyclic aromatic hydrocarbons, and also high levels of heterocyclic amines. Both groups of chemicals have been suggested to increase the risk of ESCC[45, 46]. After stratification by fried foods, we found that the protective effect of the n-3 LC-PUFA pattern was weakened in those who regularly consumed fried foods and differed from those who did not regularly consume fried foods.
The role of alcohol use in the etiology of carcinoma of the esophagus is well established. Lots of studies conducted in Kenyan , Japan, have provided further evidence of the close and independent role of alcohol in the etiology of ESCC. Many epidemiological studies have shown that alcohol is associated with tumor suppressor gene promoter hypermethylation and global DNA hypomethylation in several cancers, including esophageal. In this study, there was heterogeneity in the association between the LC-UFA pattern and ESCC, as shown in the previous study, alcohol consumption would increase the risk of pattern 2, and the association was distinct.
To the best of our knowledge, this is the first study that factor analysis has been used to reveal a causal relationship between dietary FAPs and ESCC risk in the Chinese population. In our daily life, people eat a diet made up of a variety of fatty acids, not just one kind of fatty acid. Therefore, it is important to consider the FAP analysis because it can reflect the actual dietary quality and summarize the effects of various dietary FAs. As compared with the traditional approach of analyzing single FA, factor analysis allows investigating the relationship between dietary habits and cancer accounting for complex interactions between dietary components.
Whereas, several limitations should be acknowledged in our study. Selection bias may exist in any hospital-based case-control study. However, all subjects were recruited from two hospitals according to strict criteria, which may minimize the selection bias. The study data were obtained from interviews and might lead to recall bias which may limit the accuracy of our results. To alleviate this effect, we performed face-to-face interviews and given the definitions of variables. Notwithstanding these limitations, to our knowledge, this is the first study to examine the effects of FACPs on the risk of ESCC.(3144 words)