Genetic mutations greatly increase the risk for subsequent cancers among childhood cancer survivors not treated with radiation therapy, according to a study presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting.1

Childhood cancer survivors are at an increased risk of developing subsequent unrelated cancers, which is believed to be a result of cancer treatment. The purpose of this study was to determine whether genetic predisposition plays a role in developing subsequent cancers in this population.

The researchers performed whole genome and exome sequencing, and collected clinical data including treatment exposures and pathology for 2988 patients from the St Jude Lifetime Cohort who survived various types of childhood hematologic and solid cancers for at least 5 years.

A total of 1062 subsequent cancers were diagnosed in 437 patients, with 98 patients developing at least 2 histologically distinct cancers.

The median duration between the childhood cancer and development of the subsequent cancer was 29.2 years, and the median age at diagnosis of the subsequent cancer was 38.2.

The most common subsequent cancers were basal cell carcinoma, meningioma, thyroid cancer, and breast cancer.

Mutations in known genes associated with childhood cancers such as RB1 in retinoblastoma survivors, NF1 in central nervous system embryonal tumor survivors, SUF in medulloblastoma survivors, and WTI in Wilms tumor survivors were present in 12%.1,2 Other commonly mutated genes among survivors included BRCA1, BRCA2, and TP53.

In the cohort, 5.7% of patients harbored a novel pathogenic or likely pathogenic mutation in a cancer predisposition gene. There were 62 subsequent cancers among 4% of 1326 survivors not exposed to radiation therapy.

Of those cancers, 24.2% occurred in patients with mutations in cancer predisposition genes, resulting in an increased risk of developing a subsequent cancer (odds ratio [OR], 5.6; 95% CI, 2.6-12.0; P < .001) and conferring a 23.6-fold increased risk of developing 2 different subsequent cancers (95% CI, 5.4-102.7; P < .001).

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Based on these findings, the authors recommended in a press release that “survivors of childhood cancer who develop specific types of subsequent neoplasms receive genetic counseling.” They also stated that their findings may contribute to personalized treatment decisions in the future, though additional studies are needed to confirm these findings in other childhood survivor populations.

References

  1. Wang Z, Wilson CL, Easton J, et al. Germline mutations in cancer predisposition genes and risk for subsequent neoplasms among long-term survivors of childhood cancer in the St. Jude Lifetime Cohort. Paper presented at: American Association for Cancer Research Annual Meeting 2017; April 1-5, 2017; Washington, D.C.
  2. Many childhood cancer survivors carry mutations in cancer predisposition genes, raising risk of later disease [news release]. Washington, DC: American Association for Cancer Research; April 3, 2017. http://mb.cision.com/Public/3069 /2224884/80c9a935e554ba13.pdf. Accessed April 4, 2017.