’s Lifetime Cohort study, and in light of the findings, researchers recommend enhanced genetic screening and counselling for such patients. The mean age of the patients was 36 years. They had been treated between 1962 and 2010 and had survived childhood cancer for at least 5 years.
Whole-genome sequencing performed on 156 genes associated with elevated cancer risk, including 60 cancer predisposition genes, found that 11.5% of the cohort had a pathogenic or likely pathogenic mutation.
A total of 448 patients had already been diagnosed with a subsequent cancer (SC). Of these patients, 93 had been diagnosed with more than one, noted co-investigator Zhaoming Wang, PhD, also from St. Jude’s, who presented the findings.
Researchers estimate that “more than 32,000 of the more than 400,000 childhood cancer survivors in the US are at risk for second or even third cancers because they carry mutations in known cancer predisposition genes.”
Although such mutations do not always lead to cancer, survivors who carried high-risk mutations and had also received radiation therapy for paediatric cancer had more than an 11-fold increased risk of developing secondary breast cancer or sarcoma compared to frequency-matched community control persons (P < .001) and more than a fourfold increased risk for thyroid cancer (P = .02).
Survivors with high-risk mutations who had not received prior radiation had a sevenfold increased risk for breast cancer (P = .004) and a 4.6-fold increased risk for any SN (P < .001).
Among survivors with high-risk mutations, risk for multiple SNs was increased 11.5-fold among patients who had undergone radiation therapy (P = .002); it was increased 2.5-fold for patients who had not received radiation (P = .04).
Dr Robison went on to say: “We feel that at this point, our data are able to identify the high-risk groups within the paediatric cancer survivor population (i.e., those with an SN without radiation and those with specific types of SN that occur within a radiation field).
Given that approximately 80% of cases do not have a mutation, we feel that at this point we cannot recommend that all patients receive genetic counselling unless there are other indications, such as a family history or indications of a genetic syndrome,”
Dr John M. Maris, MD, professor of paediatrics at the University of Pennsylvania’s Perelman School of Medicine, in Philadelphia, who was not involved in the study but was asked to comment, said:
“This is a very important study that further refines our understanding of why children develop cancer in the first place, but also why survivors may be at increased risk for a subsequent new malignancy.
The fact that 11.5% of survivors may be at a significantly increased risk is sobering, but even more worrisome is that this study may be the proverbial tip of the iceberg, as they have not yet analyzed the majority of the genome, so we will be looking forward to follow-up reports from this group.”