Dysregulated Phosphate Metabolism, Periodontal Disease, and Cancer: Possible Global Health Implications.

Ronald B Brown

doi:10.3390/dj7010018

Abstract

An association between periodontal disease and cancer has been established in recent studies, but no common etiology has been identified in the hopes of reducing the global burden of these non-communicable diseases. This perspective article hypothesizes that the determinant mediating the association of periodontal disease with cancer is dysregulated phosphate metabolism. Phosphate, an essential dietary micronutrient, is dysregulated in chronic kidney disease, and both cancer and periodontal disease are associated with chronic kidney disease. Reviewed evidence includes the association between phosphate toxicity and cancer development, and the association between periodontal disease and chronic kidney disease-mineral and bone disorder includes conditions such as ectopic calcification and bone resorption, which may be indirectly related to periodontal disease. Dental calculus in periodontal disease contains calcium phosphate crystals that are deposited from excess calcium and phosphate in saliva. Alveolar bone resorption may be linked systemically to release of parathyroid hormone in response to hypocalcemia induced by hyperphosphatemia. More research is needed to examine the role of dysregulated phosphate metabolism in periodontal disease.

Highlights

The global burden of periodontal disease, which accounts for the majority of the 442 billion USD spent on oral disease costs, share risk factors, and social determinants with other non-communicable diseases such as diabetes, heart disease, and cancer [1]
Recent studies investigating the link between periodontal disease and various cancers include meta-analyses of periodontal disease and cancer [2,3], studies of periodontal disease and cancer in postmenopausal women [4,5], in male non-smokers [6], and studies and meta-analyses of periodontal disease linked to specific cancers including breast cancer [7,8], pancreatic cancer [9,10], oral cancer [11,12], colorectal cancer [13,14], lymphoma [14,15], head and neck cancer [16], lung cancer [17,18], prostate cancer [19], and gastric cancer [20]
Explaining a common cause linking periodontal disease with cancer has possible global health implications, suggesting that a reduction in the global burden of these non-communicable diseases may be possible by modifying their common lifestyle risk factors and determinants

Summary

Introduction

The global burden of periodontal disease, which accounts for the majority of the 442 billion USD spent on oral disease costs, share risk factors, and social determinants with other non-communicable diseases such as diabetes, heart disease, and cancer [1]. Despite consistent findings supporting a positive association between periodontal disease and cancer, replete with hypotheses implicating oral microorganisms and systemic inflammation, a common causal mechanism has not been identified in the etiology of these two non-communicable. It is not clear if periodontal disease causes cancer, or cancer causes periodontal disease, or some other common pathophysiological determinant causes both diseases This perspective article reviews evidence supporting a novel hypothesis that the association of periodontal disease with cancer may be mediated by the pathophysiological determinant of dysregulated phosphate metabolism. The discovery of a common cause linking periodontal disease and cancer has possible global health implications, suggesting a reduction in the global burden of these non-communicable diseases by modifying their common lifestyle risk factors and determinants

Phosphate Toxicity as a Global Health Burden

Dysregulated Phosphate Metabolism and Cancer

Periodontal

Chronic Kidney Disease-Mineral and Bone Disorder

Conclusions