Association of Esophageal Squamous Cell Carcinoma With the Interaction Between Poor Oral Health and Single Nucleotide Polymorphisms in Regulating Cell Cycles and Angiogenesis: A Case-Control Study in High-Incidence Chinese

Abstract

Introduction Oral health and genetic factors can independently influence the risk of developing esophageal squamous cell carcinoma (ESCC). Objectives The primary objective of this study was to investigate the interactive effects of oral health and genetic factors on ESCC risk. Methods This was a matched case-control study with 927 ESCC patients and 1701 matched controls. We selected 101 candidate single nucleotide polymorphisms (SNPs) from 59 genes that were associated with ESCC. Oral health was assessed based on tooth-brushing frequency, tooth loss, and age at the time of first tooth loss. An unconditional logistic regression model was employed in which SNP–oral health interactions were assessed as risk factors for ESCC, after adjusting for age and sex. A genetic risk score (GRS) analysis was conducted. Results The association between GRS and ESCC and the synergistic effect of GRS and oral health on ESCC were examined. Daily frequency of tooth-brushing was found to interact with 5 SNPs, rs3765524, rs753724, rs994771, rs3781264, and rs11187842, to increase the risk of ESCC. In particular, individuals with genotype TT of rs3765524 who brushed their teeth less than twice a day had a 5.13-times higher risk of ESCC than those with genotype CC who brushed their teeth at least twice a day. Furthermore, tooth loss interacted with two SNPs: rs1159918 from ADH1B and rs3813867 from CYP2E1. Conclusion Oral health may interact with genetic factors increasing ESCC risk, which provides new insights into the relationship between ESCC and gene–lifestyle interactions which can be used for disease prevention.