Elsevier

Oral Oncology

Volume 51, Issue 4, April 2015, Pages 332-340
Oral Oncology

Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: A meta-analysis of observational studies

https://doi.org/10.1016/j.oraloncology.2015.01.003Get rights and content

Summary

Objective

Associations between type 2 diabetes mellitus (type 2 DM) and risk of oral cancer and precancerous lesions have been reported with controversial findings. We performed a meta-analysis to explore these associations.

Methods

We identified studies by a literature search of MEDLINE and EMBASE through May 31, 2014, and by searching the reference lists of pertinent articles. Summary relative risk (SRR) with 95% confidence interval (CI) was calculated with a random-effects model. Between- study heterogeneity was assessed using the Cochran’s Q and I2 statistics.

Results

A total of 13 studies (4 case-control and 9 cohort studies) on the association between type 2 DM and oral cancer were included. Overall analysis found that compared with non-diabetic individuals, individuals with type 2 DM had a significantly elevated incidence of oral cancer (SRR = 1.15, 95% CI: 1.02–1.29; Pheterogeneity = 0.277, I2 = 15.4%; 10 studies). Subgroup analyses found that duration of follow-up (⩾11 years) significantly altered this positive association. Type 2 DM was associated with increased oral cancer mortality (SRR = 1.41, 95% CI: 1.16–1.72; 4 studies). Meta-analysis of the four case-control studies showed a positive association between type 2 DM and risk of oral precancerous lesions (SRR = 1.85, 95%CI: 1.23–2.80; Pheterogeneity = 0.038, I2 = 57.5%). No significant public bias was found across these studies.

Conclusions

These findings of this meta-analysis indicate that compared with non-diabetic individuals, individuals with type 2 DM have an elevated risk of oral cancer and precancerous lesions development.

Introduction

Oral cancer (OC) represents the eighth most frequent cancer worldwide, which includes cancers of the lip, gums, tongue, soft hard palate, etc. [1]. The geographic area with the highest incidence and mortality from this deadly disease is Melanesia, followed by south central Asia. In China, oral cancer was reported 3.29 per 100,000 as incidence rate and 1.49 per 100,000 as mortality rate in 2008 [2]. Despite the advances in diagnosis and treatment, the 5-year survival rate for patients with OC is still low in many parts of the world [3]. Oral precancerous lesions have been well recognized as the precursors of oral cancer [4], which include oral leukoplakia, erythroplakia, and submucous fibrosis, etc. Recently, progresses have been made through epidemiological studies investigating environmental risk factors for oral cancer and precancerous lesions, and the well documented factors include cigarette smoking, alcohol consumption, betel-quid chewing and some types of viral infections [5], [6], [7], [8].

It has been shown that type 2 diabetes (type 2 DM) are risk factors for several malignancies, including cancers of the breast [9], endometrium [10], pancreas [11], [12], and liver [13]. The hypothesized biological mechanisms is related to the effect of insulin and insulin-like growth factors (IGFs) axis, which would trigger intracellular signaling cascades with mitogenic and antiapoptotic effects [14]. Additionally, the inflammation-mediated carcinogenesis is also a well-known empirical fact [14].

Is there any correlation between type 2 DM and carcinogenesis of the oral cavity? Inconsistent results have been reported for these associations [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31]. Campbell and his coauthors prospectively enrolled a cohort of 1,053,831 U.S. adults, and observed a total of 1182 deaths from oral cancers after 28 years of follow-up [29]. Diabetic men had a significant risk of OC mortality than did non-diabetic men (relative risk [RR] = 1.44, 95% confidence interval [CI]:1.07–1.94), while diabetic women had a non-significantly increased risk than non-diabetic women (RR = 1.43, 95%CI: 0.94–2.20). Similar results were also observed in the study by Wideroff et al. [17]. However, a non-significantly increased risk association between diabetes and OC was observed in most of the included studies, and even, a significantly inverse association was shown in the study by Hjalgrim et al. [16].

The purpose of the present study was to summarize all available evidence from observational studies to estimate the risk of oral cancer and precancerous lesions in patients with type 2 DM following the meta-analysis of observational studies in epidemiology (MOOSE) guidelines [32].

Section snippets

Data sources and searches

To identify relevant studies, two investigators (G.Y.H. and W.B.J.) independently conducted a systematic literature search of MEDLINE (from January 1, 1966) and EMBASE (from January 1, 1974), through May 31, 2014. In addition, a manual review of references from primary or review articles was performed to identify any additional studies. The relevant studies were searched with the following text word and/or Medical Subject Heading (MeSH) terms: (1) “diabetes”; (2) “oral cancer” OR “oral

Search results, characteristics and quality assessment

The search strategy generated 831 citations of which 29 were considered of potential value and the full text was retrieved for detailed evaluation (Fig. 1). Eighteen of these 29 articles were subsequently excluded: 11 studies did not evaluate this association, 3 studies reported the same population, 3 studies did not report RR and/or 95%CI, and 2 studies reported young-onset DM. Additional 6 articles were included from reference review. Thus, a total of 17 articles provided data to investigate

Discussion

The current meta-analysis, which is the first and most comprehensive to date, indicate that compared with non-diabetic individuals, individuals with type 2 DM have an approximately 15% increased risk of oral cancer development, and the increased risks were statistically significant after adjusting for tobacco and alcohol use, two major risk factors for this cancer. Type 2 DM may also increase OC mortality. In addition, only limited evidence from four case-control or cross sectional studies

Conflict of interest statement

There are no conflicts of interest to declare.

Acknowledgements

No funding.

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