Acquired DNA damage in adolescent obesity – a promoter and predictor of cancer?

Introduction Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity coincides with deficiencies in micronutrients such as Vitamin D, a key player in DNA repair processes. As a result, vitamin D deficiency in obesity may have a marked impact on DNA stability and integrity. 8-hydroxyguanosine (8-OHdG) is a well-established marker of oxidative DNA damage that has been identified in higher concentrations in cancer patients. Here we report, preliminary, unpublished findings from our study on acquired DNA damage in childhood obesity. Material and Method Body Mass Index (BMI), Waist to Hip ratio (WHR) and body fat percentage via bioelectrical impedance was assessed in over 70 participants, aged 11-18 and recruited from National Health Service (NHS) obesity clinics and schools in London. A non-invasive, integrated evaluation of urinary 8-OHdG and salivary vitamin D was conducted using ELISA based methods and compared to markers of adiposity. Results and Discussion A BMI percentile >99 was found to be associated with decreased salivary vitamin D and increased urinary 8-OHdG when compared to healthy weight controls (BMI = 5th-85th percentile). Vitamin D levels in saliva were found to be inversely correlated with BMI and body fat percentage. Urinary 8-OHdG positively correlated with body fat percentage and WHR. Most importantly, an inverse correlation between vitamin D in saliva and 8-OHdG in urine was also identified. Recent evidence has suggested vitamin D in obesity to be a consequence of altered behaviour, reduced intestinal absorption, and sequestration of vitamin D into adipose tissue. As a result, DNA repair processes against oxidative DNA damage in obesity may be impaired, resulting in the excess of lesions including 8-OHdG. The effects of excess 8-OHdG lesions have been well researched to include various mutations that can drive carcinogenesis. Conclusion Our results suggest Vitamin D deficiency in obese adolescents may play a significant role in triggering oxidative DNA damage, thus increasing the likelihood of cancer later in life