Childhood cancer survivors are at risk for traditional cardiovascular risk factors (CVRFs), independent of their underlying genetic risk and their cancer treatment, according to research published by the Journal of the National Cancer Institute.
Childhood cancer survivors are at risk for developing CVRFs including insulin resistance, atherogenic dyslipidemia, and hypertension, study researchers explained, but, unlike many late outcomes that are strongly linked to primary cancer therapy exposure, “the attributable risk percent of the association of cancer treatment with risk for CVRFs in CCS [childhood cancer survivors] is modest, suggesting that genetic and lifestyle factors may play a relatively greater role.”
In this cohort analysis, researchers studied childhood cancer survivors from the St. Jude Lifetime Cohort Study who were aged at least 18 years, were diagnosed with a childhood cancer at least 5 years previously, and had European ancestry.
The researchers explained that they made the decision to restrict eligibility in this way because “most PRSs [polygenic risk scores] developed in the general population have been predominantly developed for individuals of European ancestry.”
Traditional CVRFs were examined as continuous variables, rather than using established cutoffs, and the researchers selected 4 lifestyle factors — smoking, physical activity, diet, and obesity — for the analysis, as previous studies had shown that they are associated with CVRFs. Standard questionnaires and measures were used to assess the 4 factors.
In all, 5635 childhood cancer survivors met the inclusion criteria. The mean age of the patients at diagnosis was 8.4 years, the average age at follow-up was 34.6 years, and the mean length of follow-up was 23.3 years. The most common childhood cancer diagnosis was acute lymphoblastic leukemia (34.5%), followed by Hodgkin lymphoma (13.2%) and central nervous system tumors (9.7%).
Radiotherapy was used in 52.6% of participants, with 31.4% receiving treatment to the cranium, 23.0% to the chest, and 21.5% to the neck. In addition, 74.4% of patients underwent chemotherapy with plant alkaloids, 60.6% with anthracycline antibiotics, and 59.7% with alkylating agents.
The analysis revealed that both lifestyle and genetic risk, as assessed via whole-genome sequencing on DNA extracted from blood samples, were associated with CVRFs.
For example, childhood cancer survivors with a “good” lifestyle had a mean systolic blood pressure (SBP) of 126.1 mmHg, compared to 133.9 mmHg for those with a “poor” lifestyle. Childhood cancer survivors with a low genetic risk had a mean SBP of 127.1 mmHg compared to 132.4 mmHg in those with a high genetic risk. The results were similar when the patients were stratified by cancer therapy received.
Sensitivity analysis indicated that childhood cancer survivors with a high genetic risk had a 5.0 mmHg higher SBP than those with a low genetic risk, while those with a “poor” lifestyle had a 5.4 mmHg higher SBP than those with a “good” lifestyle. The respective figures for diastolic blood pressure (DBP) were 4.4 mmHg and 3.4 mmHg.
When they stratified the analysis by genetic risk status, the researchers found that, among childhood cancer survivors with a high genetic risk, the average DBP was 4.6 mmHg lower in those with a “good” lifestyle compared to those with a “poor” lifestyle (P =.034), while fasting glucose was lower by an average of 5.0 mg/dL (P =.018).
In childhood cancer survivors with an intermediate genetic risk, mean SBP was 6.3 mmHg lower in those with a “good” lifestyle compared to those with a “poor” lifestyle (P <.001), while average DBP levels were 2.8 mmHg lower (P <.001), and fasting glucose levels were lower by 1.6 mg/dL (P =.051).
“Although our findings are consistent with studies from the general population that demonstrate that lifestyle, despite underlying genetic risk, can impact the risk of a range of conditions … our study demonstrates that among CCS, a healthy lifestyle may partially ameliorate perturbations in CVRFs following both exposure to risk-increasing cancer therapies and high genetic risk,” the researchers concluded.
“Thus, our findings highlight the importance of future intervention research targeting modifiable health behaviors among CCS,” the researchers added.
Disclosures: This research was supported by the American Lebanese Syrian Associated Charities and the National Institutes of Health. The study authors reported having no conflicts of interest. Please see the original reference for complete disclosures,
This article originally appeared on Cancer Therapy Advisor