May 11, 2015
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Pediatric cancer treatments increase risk for obesity in adulthood

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Survivors of pediatric cancers who received cranial radiation or glucocorticoids appeared more likely to be obese later in life, according to study results.

“Obesity is problematic because it increases susceptibility to chronic diseases and premature mortality,” Kirsten K. Ness, PT, PhD, of St. Jude Children’s Research Hospital, and colleagues wrote. “Weight gain accelerates with age, and it is hypothesized that weight gain is associated with radiation-induced damage to the hypothalamic-pituitary axis, leading to alterations in leptin sensitivity or growth hormone production.”

Ness and colleagues evaluated data from 1,996 survivors of pediatric cancers (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Fifty-one percent of the population was male and 86.5% were white. All participants survived for 10 years or longer after diagnosis and previously received treatment at St. Jude Children’s Research Hospital.

Researchers evaluated the risk for obesity — defined as a BMI of 30 kg/m2 or greater — based on previous treatment with glucocorticoid, anthracycline and alkylating agents and/or cranial, chest, abdominal and pelvic radiation. Because previous studies suggested a strong link between cranial radiation and obesity, researchers stratified participants according to cranial radiation therapy.

Median follow-up from diagnosis was 24.6 years.

At the time of evaluation, 36.2% (n = 723) of survivors of childhood cancer were obese, 27.9% (n = 556) were overweight, 32.3% (n = 645) were of normal weight and 3.6% (n = 71) were underweight.

Among men, obesity was more prevalent among survivors of leukemia (42.5%) and other tumors (38.8%), whereas female survivors of neuroblastoma (43.6%) and leukemia (43.1%) were more likely to be obese.

Obesity was more common among survivors who were aged 5 years or younger at diagnosis (men, 40.4%; women, 39.5%) and among those who had survived for more than 30 years from diagnosis (45%).

Forty-seven percent of survivors who underwent cranial radiotherapy were obese at the time of evaluation, compared with 29.4% of participants who had not (P < .001).

Results of a multivariable analysis indicated obesity was significantly associated with cranial radiation (P < .001), exposure to glucocorticoid (P = .004) and being aged 30 years or older at time of evaluation (P < .001).

However, undergoing chest, abdominal or pelvic radiation was linked to a significantly decreased prevalence of adult obesity (P < .001).

Among survivors who underwent cranial radiation, older age at follow-up (≥ 30 years vs. ≤ 30 years; P = .003), younger age at diagnosis (0-4 years vs. ≥ 15 years; P = .013) and glucocorticoid therapy (P = .014) were significantly associated with increased rates of obesity. However, only older age at follow-up was significantly associated with obesity among survivors who did not undergo cranial radiotherapy (P < .001).

Researchers also identified 166 single nucleotide polymorphisms associated with the development of obesity among survivors who underwent cranial radiation using a type I error rate of 5 x 10-6. Researchers observed the greatest association in reference SNP rs35669975 (P = 3.3 x 10-8), on segment 33.3 of the long arm of chromosome 13 downstream of FAM155A. Other genes identified — including GLRA3, SOX11 and CDH18 — were associated with neural growth, repair and connectivity.

The researchers acknowledged their small sample size and the potential inaccuracy of BMI as a measurement for adiposity may be limitations to these findings.

“The ability to identify patients at increased risk for obesity on the basis of genetic susceptibility may improve early detection in high-risk subgroups,” Ness and colleagues concluded. “The high prevalence of obesity among survivors underscores the need for immediate focus on research directed at developing effective interventions for weight measurement to optimize health outcomes among survivors of childhood cancer as the age.” – by Cameron Kelsall

Disclosure: One researcher reports receiving personal fees from Novo Nordisk.

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