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      Dental fluorosis and oral health in the African Esophageal Cancer Corridor: Findings from the Kenya ESCCAPE case–control study and a pan‐African perspective

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          Abstract

          There are no studies of oral health in relation to esophageal cancer in Africa, or of Eastern Africa's endemic dental fluorosis, an irreversible enamel hypo‐mineralization due to early‐life excessive fluoride intake. During 2014–18, we conducted a case–control study of squamous cell esophageal cancer in Eldoret, western Kenya. Odds ratios (AORs (95% confidence intervals)) were adjusted for design factors, tobacco, alcohol, ethnicity, education, oral hygiene and missing/decayed teeth. Esophageal cancer cases (N = 430) had poorer oral health and hygiene than controls (N = 440). Compared to no dental fluorosis, moderate/severe fluorosis, which affected 44% of cases, had a crude OR of 20.8 (11.6, 37.4) and on full adjustment was associated with 9.4‐fold (4.6, 19.1) increased risk, whilst mild fluorosis (43% of cases) had an AOR of 2.3 (1.3, 4.0). The prevalence of oral leukoplakia and tooth loss/decay increased with fluorosis severity, and increased cancer risks associated with moderate/severe fluorosis were particularly strong in individuals with more tooth loss/decay. Using a mswaki stick (AOR = 1.7 (1.0, 2.9)) rather than a commercial tooth brush and infrequent tooth brushing also independently increased risk. Geographic variations showed that areas of high esophageal cancer incidence and those of high groundwater fluoride levels have remarkably similar locations across Eastern Africa. In conclusion, poor oral health in combination with, or as a result of, high‐altitude susceptibility to hydro‐geologically influenced dental fluorosis may underlie the striking co‐location of Africa's esophageal cancer corridor with the Rift Valley. The findings call for heightened research into primary prevention opportunities of this highly fatal but common cancer.

          Abstract

          What's new?

          To date, there are no comprehensive studies of oral health and esophageal cancer in Eastern Africa, nor of this area's endemic dental fluorosis, an irreversible enamel hypo‐mineralization due to early‐life excessive fluoride intake. Here, the authors found that moderate/severe fluorosis is associated with a ten‐fold increased cancer risk in Eastern Africa, particularly if tooth loss or decay is co‐present. The finding is striking because of the remarkable co‐location of Africa's esophageal cancer corridor with areas of high groundwater fluoride. Identification of the causal mechanisms will be critical to primary prevention of this common cancer.

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          Most cited references29

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          Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China.

          Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCC) were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian.
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            Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study.

            Studies suggest that tooth loss and periodontal disease might increase the risk of developing various cancers; however, smoking might have confounded the reported associations. We aimed to assess whether periodontal disease or tooth loss is associated with cancer risk. The analysis was done in a prospective study (the Health Professionals Follow-Up Study [HPFS]), which was initiated in 1986 when US male health professionals aged 40-75 years responded to questionnaires posted by the Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA. In addition to the baseline questionnaires, follow-up questionnaires were posted to all living participants every 2 years and dietary questionnaires every 4 years. At baseline, participants were asked whether they had a history of periodontal disease with bone loss. Participants also reported number of natural teeth at baseline and any tooth loss during the previous 2 years was reported on the follow-up questionnaires. Smoking status and history of smoking were obtained at baseline and in all subsequent questionnaires. Additionally at baseline, participants reported their mean frequency of food intake over the previous year on a 131-item semiquantitative food-frequency questionnaire. Participants reported any new cancer diagnosis on the follow-up questionnaires. Endpoints for this study were risk of total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazard models according to periodontal disease status and number of teeth at baseline. In the main analyses, 48 375 men with median follow-up of 17.7 years (1986 to Jan 31, 2004) were eligible after excluding participants diagnosed with cancer before 1986 (other than non-melanoma skin cancer, n=2076) and those with missing data on periodontal disease (n=1078). 5720 incident cancer cases were documented (excluding non-melanoma skin cancer and non-aggressive prostate cancer). The five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). After adjusting for known risk factors, including detailed smoking history and dietary factors, participants with a history of periodontal disease had an increased risk of total cancer (HR 1.14 [95% CI 1.07-1.22]) compared with those with no history of periodontal disease. By cancer site, significant associations for those with a history of periodontal disease were noted for lung (1.36 [1.15-1.60]), kidney (1.49 [1.12-1.97]), pancreas (1.54 [1.16-2.04]; findings previously published), and haematological cancers (1.30 [1.11-1.53]). Fewer teeth at baseline (0-16) was associated with an increase in risk of lung cancer (1.70 [1.37-2.11]) for those with 0-16 teeth versus those with 25-32 teeth. In never-smokers, periodontal disease was associated with significant increases in total (1.21 [1.06-1.39]) and haematological cancers (1.35 [1.01-1.81]). By contrast, no association was noted for lung cancer (0.96 [0.46-1.98]). Periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in never-smokers. The associations recorded for lung cancer are probably because of residual confounding by smoking. The increased risks noted for haematological, kidney, and pancreatic cancers need confirmation, but suggest that periodontal disease might be a marker of a susceptible immune system or might directly affect cancer risk.
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              Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies.

              Poor oral health has been reported as a risk factor in the etiology of head and neck cancer. Data on oral health were ascertained as part of two multicenter case-control studies comprising 924 cases and 928 controls in central Europe and 2,286 cases and 1,824 controls in Latin America. Incident cases of squamous cell carcinoma of the head and neck (oral cavity, pharynx, larynx) and esophagus, as well as age (in quinquennia)- and sex frequency-matched controls, were enrolled from 1998 to 2003. Poor condition of the mouth (central Europe: odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.74, 4.81; Latin America: OR = 1.89, 95% CI: 1.47, 2.42), lack of toothbrush use (Latin America: OR = 2.36, 95% CI: 1.28, 4.36), and daily mouthwash use (Latin America: OR = 3.40, 95% CI: 1.96, 5.89) emerged as risk factors for head and neck cancer, independent of tobacco use and alcohol consumption. Missing between six and 15 teeth was an independent risk factor for esophageal cancer (central Europe: OR = 2.84, 95% CI: 1.26, 6.41; Latin America: OR = 2.18, 95% CI: 1.04, 4.59). These results indicate that periodontal disease (as indicated by poor condition of the mouth and missing teeth) and daily mouthwash use may be independent causes of cancers of the head, neck, and esophagus.
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                Author and article information

                Contributors
                dianamenya@gmail.com
                mccormackv@iarc.fr
                Journal
                Int J Cancer
                Int. J. Cancer
                10.1002/(ISSN)1097-0215
                IJC
                International Journal of Cancer
                John Wiley and Sons Inc. (Hoboken )
                0020-7136
                1097-0215
                12 January 2019
                01 July 2019
                : 145
                : 1 ( doiID: 10.1002/ijc.v145.1 )
                : 99-109
                Affiliations
                [ 1 ] School of Public Health College of Health Sciences, Moi University Eldoret Kenya
                [ 2 ] Academic Model Providing Access to Healthcare (AMPATH) Eldoret Kenya
                [ 3 ] School of Medicine College of Health Sciences, Moi University Eldoret Kenya
                [ 4 ] University of Eldoret Eldoret Kenya
                [ 5 ] Section of Environment and Radiation International Agency for Research on Cancer Lyon France
                [ 6 ] Section of Genetics International Agency for Research on Cancer Lyon France
                Author notes
                [*] [* ] Correspondence to: Valerie McCormack, Section of Environment and Radiation, International Agency for Research on Cancer, Lyon, France, Tel.: +33 4 72 73 85 66, E‐mail: mccormackv@ 123456iarc.fr ; or Diana Menya, School of Public Health, College of Health Sciences, Moi University, Eldoret, Kenya, E‐mail: dianamenya@ 123456gmail.com
                Author information
                https://orcid.org/0000-0003-2450-8610
                https://orcid.org/0000-0001-7397-3442
                Article
                IJC32086
                10.1002/ijc.32086
                6519293
                30582155
                e57f60ed-cc2f-4638-b11c-37e5e940ddf6
                © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 02 November 2018
                : 04 December 2018
                : 13 December 2018
                Page count
                Figures: 4, Tables: 2, Pages: 11, Words: 6784
                Funding
                Funded by: European Commission FP7 Marie Curie Actions
                Funded by: IARC post‐doctoral fellowship
                Funded by: IARC‐UICC Development Fellowship
                Funded by: NIH
                Award ID: R21CA191965
                Funded by: NCI
                Award ID: R21CA191965
                Funded by: International Agency for Research on Cancer (IARC)
                Categories
                Cancer Epidemiology
                Cancer Epidemiology
                Custom metadata
                2.0
                ijc32086
                1 July 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:15.05.2019

                Oncology & Radiotherapy
                africa,cancer,esophageal cancer,dental fluorosis,oral health
                Oncology & Radiotherapy
                africa, cancer, esophageal cancer, dental fluorosis, oral health

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