Environmental Carcinogenesis:Characterization of Rising Incidence and Discovery of Novel Biomarkers of Pathogenesis and Prognosis.

Molecular Epidemiology;Cadmium Toxicity;HPV Epigenetic;Thailand;Public Health;Health Sciences;Toxicology

Virani, ShamaCote, Michael Lynn ;

University of Michigan

关键词: Molecular Epidemiology;    Cadmium Toxicity;    HPV Epigenetic;    Thailand;    Public Health;    Health Sciences;    Toxicology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/108938/shamav_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

This dissertation applied molecular epidemiology to address the relationship between the environment and cancer. The World Health Organization has identified cancer as the leading cause of death worldwide, and the International Agency for Research on Cancer shows the global burden of cancer lies primarily in low- and middle-income countries (LMICs). It is crucial to understand the effects of the surrounding environment on cancer incidence, induction and outcomes.The first objective of this dissertation was to characterize female breast cancer incidence trends in southern Thailand. Incidence rates of breast cancer increased by almost 300% from 1990 to 2010. Both period and birth cohort effects played a role in shaping the increase in incidence. Three distinct incidence projection methods consistently suggested that incidence rates will continue to increase in the future with incidence for women age 50 and above increasing at a higher rate than for women below 50. The findings from this study identify opportunities for breast cancer prevention and future research by identifying priorities for screening and developing hypotheses for population-based studies.Cadmium is a Class 1 carcinogen (IARC), however its mechanism of toxicity is unknown. My second objective was to determine epigenetic changes associated with this exposure. There are significant areas of environmental cadmium exposure in Thailand. Environmental cadmium exposure is associated with specific DNA methylation, and this relationship depended on the gender of the individual. Identification of these biomarkers of cadmium in a human population is a logical first step to identifying the mechanism of carcinogenesis. The relationship between environmental and epidemiologic factors and these changes is not well understood. Novel relationships were identified between methylation markers, survival and recurrence, and differed based upon etiologic environmental factors. Identification of these significant epigenetic markers should open new horizons for interventions directed at reversible gene alterations and new therapeutic targets. Overall, this research provides an understanding of the environmental contribution to cancer incidence, pathogenesis and prognosis. It offers a basis for future studies aimed at developing targeted interventions to address the rise in cancer incidence in Thailand, toxicity of environmental exposures and determining individualized treatment therapies to promote patient survival.