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Community-Driven Research in the Canadian Arctic: Investigating the Effect of Dietary Exposure to Methylmercury on the Severity of Chronic Inflammation and Gastric Neoplasia in Populations with an Elevated Risk of Gastric Cancer

  • Author / Creator
    Walker, Emily V
  • Introduction While gastric cancer has been declining in incidence for decades globally, it remains a major cause of death. Evidence suggests that Indigenous populations worldwide experience a higher burden of gastric cancer relative to non-Indigenous populations residing in the same geographic areas. Within Canada, community-driven research conducted by the Canadian North Helicobacter pylori (CANHelp) Working Group in western Arctic communities demonstrates a higher burden of gastric disease relative to multi-ethnic populations in southern regions. CANHelp community projects use community input to guide research aiming to address this disparity. In particular, participants have conveyed concern that the environmental contaminant mercury could be causing gastric cancer. Among the small participating communities, there were too few gastric cancer cases to investigate risk factors for cancer directly. Instead, intermediate endpoints provided a more efficient alternative; a widely accepted model of gastric carcinogenesis shows deleterious changes in the gastric mucosa are initiated by chronic gastritis, followed by gastric atrophy and intestinal metaplasia. This dissertation investigates the hypothesis that low doses of mercury ingested through fish and marine mammal consumption increases the risk of severe chronic gastritis, atrophy, and intestinal metaplasia among residents of Canadian Arctic communities. Methods Systematic literature review identified published articles presenting human tissue concentrations of mercury stratified by fish consumption frequency for meta-analyses that assessed sources of variation across studies in the relationship between mercury intake and mercury concentrations in hair. Two analyses were conducted: multivariate random-effects meta-regression of summary data reported in the literature; multivariable random-effects regression of pooled raw data provided by authors of identified reports. In fall 2016, a fish/whale-focused food-frequency questionnaire was administered to residents of participating communities. Hair samples were collected for biochemical measurement of methylmercury concentration. Methylmercury was measured in the full-length of each hair sample using gas chromatography inductively coupled plasma-mass spectrometry. Multivariable random-effects linear regression estimated beta-coefficients and 95% confidence intervals (CIs) for the effect of fish/whale consumption frequency on hair-methylmercury concentrations. Pathological assessment was facilitated by endoscopy with gastric biopsy offered in Aklavik (2008) and Fort McPherson (2012), Northwest Territories and Old Crow (2011), Yukon. A pathologist graded the severity of gastric pathologies using the updated Sydney System. Multivariable logistic regression estimated log odds, odds ratios and 95%CIs for the effect of hair-methylmercury concentration on the prevalence of severe chronic gastritis, gastric atrophy, and intestinal metaplasia. Results The systematic review identified 87 eligible articles. The analysis of summary data showed that hair mercury concentrations increase with increasing fish consumption to a degree that varies greatly across studies. Specifically, while the direction of this relationship was consistent across studies, the strength of the trend varied. The magnitude of between-study variation was not reduced by adjustment for distributions of age or sex. Analysis of pooled datasets showed similar results, with a high degree of between-study variation for all exposure contrasts, after adjusting for age and sex. In fall 2016, 101 participants provided hair samples and diet data. The mean number of different species eaten by participants was 3.50 (SD:1.90). The mean hair-methylmercury concentration was 0.60μg/g (SD:0.47). There was a positive association between consumption of fish and marine mammals in each season and hair-MeHg concentration, after adjusting for sex, hair length and use of permanent hair treatments. Among 80 participants with complete data, the proportions with severe chronic gastritis, atrophy and intestinal metaplasia were 38%, 29% and 17%, respectively. The adjusted log odds of severe chronic gastritis and atrophy were highest among those with hair-methylmercury ≥1μg/g when estimated selenium intake was 0 μg/kg body weight/week. As estimated selenium intake increased, the adjusted log odds of each outcome approached 0 for all mercury exposure levels. Conclusions Meta-analysis of summary and pooled data demonstrated that accurate assessment of exposure to mercury through diet requires consideration of factors beyond age and sex. Among participants from Canadian Arctic communities, hair-methylmercury concentrations were below the 6.0μg/g threshold for safe exposure levels defined by Health Canada, suggesting that their fish/whale consumption practices are not placing them at elevated risk of known serious health outcomes associated with exposure. However, this research yielded evidence of a relationship between higher hair-methylmercury concentrations and increased odds of severe chronic gastritis and gastric atrophy, which may be mediated and modified by selenium intake.

  • Subjects / Keywords
  • Graduation date
    2017-11:Fall 2017
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3RB6WG4C
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Medicine
  • Supervisor / co-supervisor and their department(s)
    • Goodman, Karen (Department of Medicine & School of Public health)
  • Examining committee members and their departments
    • Abnet, Christian (National Cancer Institute)
    • Yuan, Yan (School of Public Health)
    • Otto, Simon (School of Public Health)
    • Harper, Sherilee (Population Medicine)
    • Girgis, Safwat (Laboratory Medicine and Pathology)