Published OnlineFirst May 19, 2016; DOI: 10.1158/1055-9965.EPI-16-0149 Research Article Cancer Epidemiology, Biomarkers Oral Hygiene and Risk of Nasopharyngeal & Prevention Carcinoma—A Population-Based Case–Control Study in China Zhiwei Liu1, Ellen T. Chang2,3, Qing Liu4,5, Yonglin Cai6,7, Zhe Zhang8,9, Guomin Chen10, Shang-Hang Xie4,5, Su-Mei Cao4,5, Jian-Yong Shao5, Wei-Hua Jia5, Yuming Zheng6,7, Jian Liao11,Yufeng Chen9, Ingemar Ernberg12,Thomas L.Vaughan13,14, Hans-Olov Adami1,15, Guangwu Huang8,9, Yi Zeng10, Yi-Xin Zeng5, and Weimin Ye1 Abstract Background: The association between oral health and risk than 3 teeth filled versus none had adjusted ORs of 1.25 (95% of nasopharyngeal carcinoma (NPC) is largely unknown. CI, 1.06–1.49) and 1.55 (95% CI, 1.13–2.12), respectively Further understanding could shed light on potential patho- (Ptrend ¼ 0.002). Conversely, the adjusted OR for those who genic mechanisms and preventive measures. brushed teeth twice or more per day versus once or less per Methods: We conducted a population-based case–control study day was 0.62 (95% CI, 0.55–0.70). We detected a borderline in southern China between 2010 and 2014. We enrolled 2,528 significant positive association with earlier age at first adult incident NPC cases, aged 20–74 years, and 2,596 controls, randomly tooth loss. selected from the total population registers, with frequency match- Conclusion: Our study suggested a positive association ing to the 5-year age and sex distribution of the cases by geographic between some indicators of poor oral health and risk of region. We interviewed subjects using a structured questionnaire NPC. Further studies are needed to confirm whether the inquiring about oral health indicators and potential confounding findings are causal and, if so, to further explain the underlying factors. We used unconditional logistic regression to estimate mul- mechanisms. tivariate-adjusted ORs with 95% confidence intervals (CI). Impact: Improvement of oral hygiene might contribute to Results: A higher number of filled teeth was associated with reducing NPC risk. Cancer Epidemiol Biomarkers Prev; 25(8); 1201–7. an elevated risk of NPC. Individuals with 1 to 3 and more Ó2016 AACR. Introduction carcinoma (NPC) risk. Higher antigen levels of Epstein-Barr virus (EBV), a potential causative agent of NPC, were found in human Epidemiologic studies suggest that poor oral health is associ- lymphoblastoid P3HR-1 cells with culture fluid of Fusobacterium ated with increased risks for cancers of the head and neck, nucleatum (14). Poor oral health can increase the risk of NPC by esophagus, stomach, and pancreas (1–9). Although the underly- stimulating EBV replication, as suggested by the finding of higher ing mechanisms are largely unknown, pathogenic shift in the oral EBV load among individuals with periodontal disease than those microbiome could cause chronic inflammation in the aerodiges- without (15–18). Poor oral hygiene can also nurture oral bacterial tive tract (10–12), which in turn may influence cancer pathogen- overgrowth, and some oral bacteria may catalyze the production esis in this region (13). To our knowledge, few studies have of nitrosamines, which are known carcinogens for NPC develop- investigated whether poor oral health affects nasopharyngeal ment (12, 19). Only one hospital-based case–control study in 1Department of Medical Epidemiology and Biostatistics, Karolinska Guangxi,China. 12Department of Microbiology,Tumorand Cell Biology, Institutet, Stockholm, Sweden. 2Exponent, Inc., Health Sciences Prac- Karolinska Institutet, Stockholm, Sweden. 13Public Health Sciences tice, Menlo Park, California. 3Division of Epidemiology, Department of Division, Fred Hutchinson Cancer Research Center, Seattle, Washing- Health Research and Policy, Stanford University School of Medicine, ton. 14Department of Epidemiology, University of Washington, Seattle, Stanford, California. 4Department of Cancer Prevention Center, Sun Washington. 15Department of Epidemiology, Harvard T.H.Chan School Yat-sen University Cancer Center, Guangzhou, Guangdong, China. of Public Health, Boston, Massachusetts. 5State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Note: Supplementary data for this article are available at Cancer Epidemiology, Center, Guangzhou, Guangdong, China. 6Department of Clinical Lab- Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). oratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, China. 7Wuz- hou Health System Key Laboratory for Nasopharyngeal Carcinoma H.-O. Adami, G. Huang, Y. Zeng, Y.-X. Zeng, and W. Ye contributed equally to this Etiology and Molecular Mechanism,Wuzhou, Guangxi, China. 8Depart- article. ment of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. 9Key Labo- Corresponding Author: Weimin Ye, Department of Medical Epidemiology and ratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden. Phone: 468-5248- Medical University), Ministry of Education, Nanning, Guangxi, China. 6184; Fax: 468-311-101; E-mail: [email protected] 10State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese Center for doi: 10.1158/1055-9965.EPI-16-0149 Disease Control and Prevention, Beijing, China. 11Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention, Wuzhou, Ó2016 American Association for Cancer Research. www.aacrjournals.org 1201 Downloaded from cebp.aacrjournals.org on September 26, 2021. © 2016 American Association for Cancer Research. Published OnlineFirst May 19, 2016; DOI: 10.1158/1055-9965.EPI-16-0149 Liu et al. Turkey has addressed this research question and found a signif- tial controls. Of these, 730 (19 %) could not be identified. Of the icant positive association between infrequent tooth brushing or 3,202 who were identified, 138 (4%) had emigrated out of the higher number of decayed teeth and risk of NPC (20). study area, 90 (3%) were deceased or incapacitated, and 326 An unresolved question in the previous study is whether (10%) refused to participate. Of the 2,648 (83% of 3,202) residual confounding by smoking, low socioeconomic status, enrolled controls, 2,133 (81%) were initial selections from the and/or diet could explain associations with poor oral health. population registry and the other 515 (19%) were replacements Detailed information on risk factors collected in a large, popu- for noncontacted selections. By comparing the distributions of lation-based study would help facilitate the rigorous evaluation of age and sex between participating and nonparticipating controls potential behavioral risk factors for NPC. To date, however, no in the Zhaoqing area, we found that younger persons were more such study of NPC has been conducted in southern China, where likely that older persons to refuse to participate but that partic- NPC is endemic, with incidence rates over 20 per 100,000 among ipation rates were similar between males and females (data not men and 10 per 100,000 among women (21). Therefore, to better shown). understand the causes and prevent this major regional public health problem, we investigated the association between oral Data collection health and risk of NPC in a population-based case–control study An electronic structured questionnaire was used by trained set in two southern Chinese provinces with the world's highest interviewers to conduct face-to-face or audiotaped telephone incidence rates of NPC (21–23). interviews with study participants. To reduce interviewer bias, we required each interviewer to interview an approximately – Materials and Methods equal number of cases and controls; however, blinding to case control status was not feasible. Collected information covered Study population demographic characteristics, residential history, occupational The collaborative NPC Genes, Environment, and EBV study history, history of chronic ear, nose, and respiratory tract (NPCGEE) was conducted in the Zhaoqing area of Guangdong conditions, family medical history, dietary habits, cigarette Province and the Wuzhou and Guiping/Pingnan areas of Guangxi smoking, alcohol and tea drinking, and use of Chinese herbal Autonomous Region. Together, these three areas comprise 13 medicine. Questionnaire data were automatically flagged for cities/counties in southern China, with a total population of logic errors and missing values, and errors were corrected by approximately 8 million. Eligible cases were aged between 20 making comparisons against audio recordings or by recontact- and 74 years at diagnosis, living in the described geographic area, ing participants. and without a prior history of malignant disease or congenital or Questions pertaining to oral health and hygiene addressed acquired immunodeficiency. To ensure prompt and nearly com- number of teeth lost after age 20 years, use of fixed dentures, plete case ascertainment, we established a rapid case recruitment number of teeth filled, daily frequency of brushing teeth, discom- system including 10 hospitals and 2 cancer research institutions fort with eating particular foods, and food avoidance due to tooth that directly notified study investigators of newly diagnosed NPC or gum problems. Number of missing teeth after 20 years of age cases. In the Zhaoqing area, 1,528 eligible cases with NPC were was categorized into four groups: none, 1 to 3, 4 to 13, and