DNA damage in paediatric obesity: a promoter and predictor of cancer in adulthood

Obesity in children is one of the most serious, global, public health challenges of the 21st century. The accumulation of adipose tissue is associated with a range of metabolic complications including diabetes, cardiovascular disease and dyslipidaemia. Epidemiological evidence links obesity in childhood with developing certain types of cancer later in life. It is postulated that excess adipose tissue and consequent inflammation derived oxidative stress may inflict an accumulation of deleterious DNA mutations and promote genome instability and drive carcinogenesis. Furthermore, a deficiency in micronutrients that are essential for DNA repair may exacerbate this pathological state. This research combined the assessment of anthropometric, inflammatory, micro-nutritional and DNA damage biomarkers via non-invasive techniques. In total, 112 children were recruited from schools and NHS obesity clinics. Anthropometric markers assessed were waist to hip ratio, body fat percentage via bioelectrical impedance, and body mass index standard deviation scores (BMI-SDS). These markers were used to classify participants as obese or nonobese and used for correlational analysis. Inflammation and micronutrient status were determined via C-reactive protein and vitamin D Enzyme Immune Assay (EIA) in saliva. DNA damage assessments include a microscopic assessment of nuclear anomalies via the buccal cytome assay, salivary telomere length via quantitative Polymerase Chain Reaction (qPCR) and urinary 8- hydroxyguanosine (8-OHdG) via EIA. The results from this study indicate obesity to be concurrent with increased inflammation and vitamin D deficiency in this cohort of participants. In addition, obesity was associated with increased oxidative DNA damage (8-OHdG) in urine and DNA damage events in the buccal mucosa. Salivary telomere length was positively correlated with obesity and the total frequency of nuclear anomalies found in buccal epithelial cells. Furthermore, there was a negative correlation between vitamin D and the frequency of nuclear anomalies in the oral cavity. Importantly, odds ratio analysis indicates a high BMI Z-score, waist circumference, body fat percentage, salivary CRP and low salivary vitamin D to be independent risk factors for increased nuclear anomalies in the buccal mucosa. This research is the first to accrue evidence for acquired DNA damage in multiple tissues obtained non-invasively from children with obesity. Our findings instigate that biomonitoring of ‘genome health’ for pre-cancerous molecular and morphological markers in obese patients may inform prioritization and severity of clinical intervention measures to prevent malignancy.

Level dc:type.qualificationlevel

PhD thesis

Grantor dc:publisher.institution

University of Westminster

Year dc:date.issued

2020

Author dc:creator

• Usman, M.

Identifier

oai:westminsterresearch.westminster.ac.uk:qz988

OAI identifier oai:identifier

oai:westminsterresearch.westminster.ac.uk:qz988