ReviewCitrus fruits intake and oral cancer risk: A systematic review and meta-analysis
Graphical abstract
Introduction
Oral cancer accounts for over 2% of the overall burden of cancer globally, with an incidence of 300,000 cases in 2012 [1] and it is the 7th major cause of death from cancer in Europe [2]. Patients with oral cancer have a poor prognosis despite advances in treatment as they continue to present with late stage disease. Indeed, the 5-year survival rate for all oral and pharyngeal cancers is only 47% for men and 55% for women [3].
Reducing the incidence of this disease through prevention is vital due to the high morbidity rates. Discovery of new drugs or novel therapeutic approaches, designed to prevent the development of this cancer, remains an important goal for scientists. Despite continuous development of synthetic drugs which are the basis of pharmaceutical care, the plant kingdom still remains an attractive source of novel anti-cancer drugs. Indeed, a large amount of anti-cancer drugs originate from natural sources [4]. Moreover, it has been demonstrated that regular consumption of fruits and vegetables may play an important role in reducing cancer risk [[5], [6], [7], [8]]. It is estimated that a high dietary intake of vegetables and fruits (>400 g/day) could prevent at least 20% of all cancer cases [9,10]. However, other studies have cast some doubts over whether their intake is really producing these cancer risk reductions [5,11]. For instance, the results from a large European prospective cohort suggested that higher a consumption of fruit and vegetables was not associated with decreased risk of pancreatic cancer [12].
In the last decade, numerous epidemiological studies have provided evidence to suggest that regular intake of Citrus fruits may be associated with a reduced risk of all-cancers, although significant results were obtained only for prostate and pancreatic cancers [13]. Moreover, Foschi and collaborators [14] have indicated that Citrus fruits have a protective role against cancers of the digestive and upper respiratory tract, as well as Gonzalez and co-workers who have observed an inverse dose response relationship between total Citrus fruits intake and gastric cancer risk [15]. Furthermore, Bae and co-workers have provided evidence for the protective effects of a high Citrus fruit intake on risk of both gastric [16] and pancreatic cancer [17] but no association with prostate cancer risk [18]. More recently, meta-analyses have highlighted an inverse association between Citrus fruit intake and risk of the breast [19], bladder [[20], [21], [22]] and esophagus [23] cancer. In contrast, a recent systematic literature review of prospective studies showed only a marginally significant decrease in risk of esophageal cancer and a non-significant inverse association for gastric cardia cancer [24].
Due to the conflicting evidence regarding the effects of Citrus fruit intake on cancer, the aim of this systematic review and meta-analysis was to quantify the relationship between Citrus fruit intake and cancer of the oral cavity and pharynx.
Section snippets
Search strategy
The bibliographic databases Ovid MEDLINE (1946-present), EMBASE (1974-present), and Web of Science (1970-present) were searched independently by two reviewers (SC and MN) for literature related to Citrus fruit intake and risk of cancer of the oral cavity and pharynx. In order to retrieve all relevant papers, no limit was placed on search time frame. The last search was performed on September 25th, 2017.
The search strategy identified studies that contained at least one keyword or Medical Subject
Results
The flowchart for study selection is shown in Fig. 1. Following initial screening of 481 titles (397 after removal of duplicates) we identified 41 full text articles for review, of which 17 were included that examined the relationship between Citrus fruit intake and risk of cancer of the oral cavity and pharynx.
Articles excluded because they were conference abstracts or book chapters were n = 16. Records excluded after title and abstract screen were n = 340. Articles excluded after full text
Discussion
We investigated the association between Citrus fruit intake and the risk of oral cancer using a meta-analysis of existing epidemiologic studies. To the best of our knowledge, this is the first systematic review and meta-analysis of oral cancer and Citrus fruit intake. The major finding of the study suggests that dietary intake of Citrus fruits plays an important protective role in the prevention of oral cancer with a pooled OR 0.50 (95% CI 0.43–0.59) for those in the highest category of intake.
Conflict of interest statement
The authors declare that the research was carried out in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
Author contributions
SC: performed the systematic literature search, data extraction, statistical analysis and drafting the paper;
MN: conceived the study, performed the systematic literature search, data extraction, and critically revised the paper;
JVW: critically revised the paper;
MMC: conceived the study, performed data extraction and critically revised the paper.
All authors read and approved the final manuscript.
Declarations of interest
None.
Sources of support
A fellowship from the “Prof. Antonio Imbesi” Foundation, Messina, Italy to S. Cirmi is gratefully acknowledged.
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