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Obesity significant predictors of genomic instability associated with cancer

A study led by the University of Westminster has found greater evidence of genomic instability, a well-recognised enabler of cancer, in children and adolescents with obesity than those with a normal range body mass index (BMI). They found that obesity, oxidative DNA damage and vitamin D deficiency are significant predictors of genomic instability.

By utilising a non-invasive approach to sample collection and through statistical modelling, the researchers have found that levels of genomic instability can be predicted by combining BMI status, vitamin D levels in saliva and measurements of DNA damage in urine. The study, ‘Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents, published in the International Journal of Obesity, is the first of its kind to make a combined, non-invasive assessment of genomic instability, vitamin D deficiency and inflammation in relation to multiple indicators of body fat in children and adolescents.

In addition, they identified that high levels of body fat markers were associated with high levels of inflammation and DNA damage, and with low levels of Vitamin D. Their findings substantiate claims that childhood obesity is associated with genomic instability and presents causative implications for increased risk of cancer in adulthood.

As a result, the researchers highlighted the need for accelerated action towards the development of effective weight loss interventions in this age group.

The research was a collaborative effort between academics at the University of Westminster and Clinicians based at King's College Hospital and St George's Hospital.

"The study involved 132 children and adolescents aged 10-18 and used quantitative measurements of the body composition of participants including BMI Z-score, waist and hip circumference, and body fat percentage,” explained first author, Dr Moonisah Usman. “Inflammation and vitamin D levels in saliva and DNA damage through urine and cheek swab samples were also assessed to score for genomic instability.”

Comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p<0.001). In addition, significant differences were also observed in some measures of genomic instability (p<0.001). Markers of adiposity positively correlated with acquired oxidative DNA damage (p<0.01) and genomic instability (p<0.001), and negatively correlated with vitamin D (p<0.01), after examining relationships between variables for all participants. Multiple regression analyses identified obesity (p<0.001), vitamin D (p<0.001) and oxidative DNA damage (p<0.05) as the three significant predictors of genomic instability.

The study draws on previous studies which have demonstrated that excess fat can result in higher levels of inflammation and nutritional deficiencies, leading to a harmful environment for DNA integrity and stability. Genome health is known to be essential for correct cellular functioning and is directly related to human health as a whole. For instance, accumulation of DNA damage and genomic instability are well recognized enablers of cancer.

"Predictive modelling based on these findings could assist clinicians in interpreting the significance of weight loss interventions in children and adolescents, and support them with prioritising the provision of further clinical measures to help reduce the risk of cancer later in life,” added Dr Emanuela Volpi, Reader in the School of Life Sciences and lead author of the study.

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