Congenital Anomalies in the Children of Cancer Survivors: A Report From the Childhood Cancer Survivor Study

• Authors: Lisa B. Signorello, International Epidemiology Institute; John J. Mulvihill, University of Oklahoma; Daniel M. Green, St Jude Children's Research Hospital; Heather M. Munro, International Epidemiology Institute; Marilyn Stovall, University of Texas MD Anderson Cancer Center; Rita E. Weathers, University of Texas MD Anderson Cancer Center; Ann Mertens, Emory University; John A. Whitton, Fred Hutchinson Cancer Research Center; Leslie L. Robison, St Jude Children's Research Hospital; John D. Boice, University of Texas MD Anderson Cancer Center
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 30, Number 3
• Publisher: American Society of Clinical Oncology | 2012-01-20, Pages 239-245
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.2011.37.2938
• Subjects: Health Sciences, Oncology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; LONG-TERM SURVIVORS; REPRODUCTIVE OUTCOMES; PREGNANCY OUTCOMES; TESTICULAR CANCER; BIRTH-DEFECTS; CHEMOTHERAPY; RADIOTHERAPY; ANEUPLOIDY; ABNORMALITIES; DISEASE

Abstract

Purpose: Children with cancer receive mutagenic treatments, which raises concern about the potential transmissibility of germline damage to their offspring. This question has been inadequately studied to date because of a lack of detailed individual treatment exposure assessment such as gonadal radiation doses. Methods: Within the Childhood Cancer Survivor Study, we performed a retrospective cohort analysis of validated cases of congenital anomalies among 4,699 children of 1,128 male and 1,627 female childhood cancer survivors. We quantified chemotherapy with alkylating agents and radiotherapy doses to the testes and ovaries and related these exposures to risk of congenital anomalies using logistic regression. Results: One hundred twenty-nine children had at least one anomaly (prevalence = 2.7%). For children whose mothers were exposed to radiation or alkylating agents versus neither, the prevalence of anomalies was 3.0% versus 3.5% (P = .51); corresponding figures were 1.9% versus 1.7% (P = .79) for the children of male survivors. Neither ovarian radiation dose (mean, 1.19 Gy; odds ratio [OR] = 0.59; 95% CI, 0.20 to 1.75 for 2.50+ Gy) nor testicular radiation dose (mean, 0.48 Gy; OR = 1.01; 95% CI, 0.36 to 2.83 for 0.50+ Gy) was related to risk of congenital anomalies. Treatment with alkylating agents also was not significantly associated with anomalies in the children of male or female survivors. Conclusion: Our findings offer strong evidence that the children of cancer survivors are not at significantly increased risk for congenital anomalies stemming from their parent's exposure to mutagenic cancer treatments. This information is important for counseling cancer survivors planning to have children.