This is the first study to report on the association between dietary patterns and OPLC risk in the Middle East and North Africa Region. The present study was conducted in Damascus, Syria, using a case–control design with 108 OPLC cases and 105 controls. Recently, there has been a growing appreciation that the overall dietary pattern, rather than any single nutrient, should be considered in relation to studying the association between diet and disease. Cancer, in particular, has complex etiology and it is unlikely that its development will be mediated by a single nutrient or food [42]. So conceptually the evaluation of the overall dietary patterns appears closer to real world as people “do not eat nutrients they eat food” [42]. In this study, using factor analysis, three dietary patterns were identified, 1) Western and 2) Traditional Syrian and 3) High Protein. Among these patterns, the Western was found to be positively associated with the odds of the OPLC. On the other hand, the Traditional Syrian and the High Protein patterns were both associated with lower odds of the cancer.
In the literature, most of the studies depicted two main patterns: A “Western” which, similar to the Western dietary pattern identified in this study, is energy dense and rich in refined grains, French fries, and sweets/desserts [42]. Another pattern also commonly reported in the literature is the “Prudent”/healthy pattern, which is generally characterised by vegetables, fruit, legumes, fish, and whole grains. In this study, instead of the commonly observed Prudent pattern, the Traditional Syrian and High Protein patterns were found. However, these patterns share significant similarities with the Prudent/healthy patterns as they consist of fruits and vegetables, fish and legumes. With the use of dietary pattern analysis becoming more widespread, traditional patterns have been identified for the ethnic or country specific diets, such as the “bean pattern” among women of Chinese or Japanese ancestry [43], the traditional Korean pattern [44], and the traditional Iranian pattern [45] and the traditional Lebanese pattern [46].
In this study, the positive association between the Western pattern and OPLC conforms to the results of similar studies. In fact, a recent study in Uruguay showed a 72 % increase in the odds of the upper aerodigestive tract cancers among subjects adhering to the Western dietary pattern. This increase was observed for oral/pharynx and larynx cancers [25]. Other studies have also shown an increase in oral cancer risk with patterns that, though had different nomenclatures, displayed many traits of the Western diet. For instance, in a case–control study in Jakarta, Indonesia, the ‘Preferred’ pattern which was associated with an almost two fold increase in the risk of oral cancer consisted of fast foods, fermented foods (including dairy), and desserts high in fat and sugar [23]. Similarly, another case–control study in Malaysia showed higher odds of oral cancer with the consumption of the ‘Combination’ pattern which consisted of dairy and meat as well as with the ‘Traditional’ pattern which included beverages and starches [7]. Many of the foods/food groups that constituted the aforementioned ‘Preferred’, ‘Combination’ and the ‘Traditional’ patterns were also shared by the Western pattern identified in our study, more specifically dairy products, starches (listed as potato, breads and pasta in our study), carbonated beverages and sugars and desserts. This observed increased in the risk of oral cancer associated with greater adherence to a Western or western-like patterns could be mediated by inflammation, the latter being a process central to most degenerative diseases including cancer. In their systematic review of the influence of dietary patterns on biomarkers of low-grade inflammation, Barbaresko et al. found that a Western pattern was positively correlated with higher concentration of C reactive proteins (CRP), a main biomarker of inflammation [47]. Furthermore, it is postulated that diets rich in high glycemic foods and protein-dense foods such as dairy products may lead to the increased formation of advanced glycated end (AGEs) products, which in turn lead to cellular damage at many levels. For instance, AGEs may cause alterations in the protein structure and function, aberrant cell signaling and dysfunction of extra cellular matrices. These damages to the normal cell functions are implicated in the etiology of most cancers including OPLC [48].
In this study, both the Traditional Syrian and the High Protein patterns were associated with significant reductions in the odds of OPLC. These findings are in line with a plethora of studies showing cancer risk reduction with a higher intake of Prudent/healthy diet, with which these patterns share many characteristics. According to the latest report by WCRF/AICR 2007 regarding the association between dietary patterns and cancer risk, recent meta-analyses (after 2007), have consistently conferred a protective effect of the prudent/healthy diet for most cancer sites, including OPLC [8]. In the Malaysian case–control study of dietary patterns and oral cancer, the ‘Prudent’ dietary pattern was associated with 47 % lower odds of the disease [7]. More recently, in Uruguay, adherence to the Prudent diet was associated with lower odds of cancers of the upper aerodigestive tract (OR = 0.52, 95 % CI = 0.34–0.76) [25]. The ‘Combination’ pattern described in the Jakarta case–control study had elements of both the Traditional Syrian and the High Protein patterns found in this study as it included red meat, fruits and poultry. Similar to our findings, adherence to this ‘Combination’ pattern was associated with 50 % decrease odds of oral cancer [23]. A closer examination of the Traditional Syrian and the High Protein patterns reveals many traits in common between these patterns with the Mediterranean diet. Syria is a country located along the side of the East Mediterranean basin and it is not surprising for its traditional dietary to have considerable similarities with the general definition of the Mediterranean diet. In fact, fruits, vegetables, olive oil, fish and legumes listed under the Traditional and High Protein dietary patterns in this study are also common denominators to most of the definitions of the Mediterranean diets [49]. The protective effects of these patterns found in this study echo the accumulating evidence pointing to a lower risk of OPLC with higher adherence to the Mediterranean diet [20, 21]. Recently, using various different indices to assess the association of OPLC with adherence to the Mediterranean diet, Filomeno et al. and Li et al. found strong evidence for a beneficial role of this diet on OPLC risk [19, 27]. A recent review by Grosso et al. discussed many plausible biological mechanisms that explain the protective role patterns such as the Prudent/healthy and the Mediterranean have on the risk of cancer [50]. Fruits and vegetables are rich in antioxidants such as carotenoids, vitamin C, vitamin E, selenium, dietary fiber (and its components), dithiolthiones, glucosinolates (isothiocyanates and indoles), polyphenols, protease inhibitors, allium compounds, plant sterols, and limonene [51]. These compounds have been shown to decrease the risk of cancer possibly through attenuation of the effects of polycyclic aromatic hydrocarbons (PAHs) and nitrosamines, preventing the progression of different cancers, inhibition of multiple cancer-related biological pathways, such as carcinogen bio-activation, cell-signaling, cell cycle regulation, angiogenesis and inflammation [52]. Tyrosol and hydroxytyrosol, two main phenolic antioxidants found in olive oil, have been linked to decrease glutathione (GSH), the activation of the transcription factor Nuclear Factor-КB and cell death which may be implicated in the carcinogenetic processes [53]. In this study, green teas and herbal infusions were also part of the Traditional Syrian dietary patterns. These hot drinks are rich sources of polyphenols, especially epigallocatechin gallate (EGCG), gallocatechin (EGC), (−)-epicatechin gallae (ECG), (−)-catechin gallate (CG), (−)-epicatechin (EC), and (+)-catechin (C) [54]. These polyphenols seem to play an important role in the reduction of cell growth, induction of apoptosis, and inhibition of angiogenesis in oral cancer cell lines [55, 56].
A main difference between the Prudent/healthy, the Mediterranean diet and the High Protein dietary pattern in this study is the fact that the latter included red meat. The association between red meat and OPLC is still controversial. A meta-analysis of observational studies investigating this association showed that while the high consumption of processed meat was significantly associated with an increased risk of oral and pharyngeal cancer, there was no significant association between total red meat and white meat intake with the risk of cancer [57]. In Syria, meat is seldom consumed as processed or canned. Smoking, curing, salting or the addition of chemical preservatives to the meat is not common practices in the country and red meat is mostly consumed as fresh cuts simmered or, less frequently, barbecued.
The current study reported a high impact of different dietary patterns on OPLC risk. This could be explained based on the present study’s population and food items. For example, in Hajizadeh et al. matched case–control study [34], conducted on an Iranian population regarding the risk of oesophageal cancer, the authors reported odds ratios of 10.3 for Western pattern and 0.17 for healthy pattern, which are both close to the current study’s reported odds ratios of Western and Traditional Syrian/High Protein dietary patterns; respectively. Both Iranian and Syrian populations are similar racially and have similar food items. Thus, these large odds ratios observed in these populations might be linked to their racial and food items characteristics.
In addition to their association with cancer, the patterns identified in this study were also investigated in association with a few socio-demographic and behavioural characteristics.
Interestingly, the results of the present study highlight gender differentials in adherence to the High Protein dietary pattern, with females being significantly more likely to adhere to this pattern compared to males. This corroborates the findings of previous studies reporting females as being more health-conscious and followers of dietary recommendations than males [46, 49, 58, 59]. In a study investigating dietary patterns among a national sample of Lebanese adults, females adhered more to the prudent pattern while males were found to mainly follow the western pattern [46]. Also, in the present study, individuals from low socioeconomic position (having low education level or not working status) were significantly less likely to adhere to healthy dietary patterns compared to individuals from high socioeconomic position. This is in line with the findings of previous studies that reported individuals from high socioeconomic position as being more followers of healthy dietary recommendations than their counterparts from low socioeconomic position [60]. Furthermore, both the Traditional Syrian and the High Protein in this study were negatively associated with smoking. This finding supports the theory that food choices are part of a larger pattern of health-related characteristics and behaviour including not smoking. In fact, previous studies have also shown that Prudent and prudent-like patterns are associated with healthy behaviour, such as, no smoking, a higher level of physical activity, breakfast consumption and regular meals pattern [61–63]. The current study’s population had a very low alcohol intake (only one subject in the cases group reported alcohol consumption). This could be explained based on the fact that the majority of Syrian population does not consume alcohol due to religious reasons.
One of the main strengths of the current study is the selection of newly diagnosed (incident) cases and population-based controls (cases’ companions [mainly family members]), which both minimised the potential selection bias inherited with prevalent cases or hospital-based controls selection [64]. Selecting hospital-based controls, from those suffering from minor ailments, not related to diet, would have had posed a serious selection bias in the current study. Such hospital-based controls might not be from the same population that generated the cases. This is due to differences in the referral patterns for different diseases in the Syrian Health Care System. The current study’s settings are the only public hospitals that provide cancer care in the southern region of Syria; whereas many other public hospitals provide care for other types of diseases and conditions. Another strength of the present study is the high participation level, both for cases and controls. The present study used a modern alternate approach to study the association between diet and OPLC in an understudied population such as in Syria. The dietary data reported and analysed were measured and collected by a trained researcher and were not self-reported, resulting in consistent interpretations and higher response and completion rates.
Despite the abovementioned strengths, the present study, like other hospital-based case–control studies, is not without limitations. Despite efforts to minimise the possibility of recall bias by blinding the participants to the current study’s specific scope, this possibility could not be completely ruled out. The present study’s effort to minimise selection bias, by recruiting population-based controls, might have had run the risk of overmatching and, hence, finding no significant differences between cases and controls. Yet, the large and significant differences, found in dietary patterns between cases and controls in the current study, suggest in the light of this possible overmatching, a rather stronger impact of identified dietary patterns on OPLC. Observer bias cannot be ruled out in the current study. The interviewer was not blinded to the present study hypothesis. Nevertheless, the appropriate training and calibration that the interviewer had received in collecting dietary data using FFQ by a strict structured interview protocol might have minimised considerably this potential bias. The reverse causality interpretation is one of the potential limitations of retrospective case–control studies. To minimise this, the current study selected new (incident) cases, where the time between the diagnosis and the referral to receive the treatment was on average less than 2 weeks. Dietary data were collected over the period of the last 12 months, therefore, the reverse causality (i.e. the presence of OPLC might have had changed the dietary patterns) is very unlikely. In contrast to matched case–control studies, the current unmatched study did not eliminate the potential confounding effect of age and gender in the design. This is because the present study targeted an understudied population, where unmatched design allowed for the exploration of the significance and impact of these socio-demographic factors, before adjusting statistically for their effect. Finally, it remains important to note that, although the FFQ used in the present study was not validated in our study population, it was previously used for the assessment of dietary patterns and their relationship with obesity and the metabolic syndrome and has yielded plausible findings among similar Arabic speaking subjects [46, 62]. In addition, the FFQ, used in the present study, was administered by a trained interviewer rather than being self-administered. This approach provides several advantages since self-administration of the FFQ requires a literate population, and may result in inconsistent interpretations of the food list and lower response and completion rates, each of which may jeopardise the validity of the data [65].
The current study’s findings can be generalised to the current study’s Syrian population. The current settings are the only public-settings that provide cancer care in the southern part of Syria.
The public health implications of the current study, both at the policy and population-based intervention levels, should be seen within a common risk factor approach perspective. The identified dietary patterns are a common determinant across a wide spectrum of cancers and other diet-related diseases. Therefore, the present study findings establish evidence to inform national health promoting policies and population-based programs in Syria.
In terms of clinical implications, the current findings imply the importance of incorporating dietary patterns assessment and advice within the general and dental practitioners’ cancer preventive care package.
