BACKGROUND/OBJECTIVES: An important late effect among females who survive childhood cancer is treatment-related ovarian damage and impaired fertility. While chemotherapy and radiation therapy are associated with impaired fertility, few other risk factors have been identified. Furthermore, little is known about the role of genetic susceptibility to these late effects. As Anti-Müllerian Hormone (AMH) is a demonstrated marker of ovarian reserve, our objective was to identify clinical and genetic predictors of AMH levels in these patients.
DESIGN/METHODS: Female survivors of childhood cancer (n=181) were recruited from the Texas Children’s Cancer Center Long-Term Survivor Program (LTSP). AMH (ng/mL) was measured using an enzyme-linked immunosorbent assay. Information on age at diagnosis and enrollment, race, ethnicity, cancer diagnosis, pelvic radiation, and use of alkylating agents was abstracted from medical records. The following single nucleotide polymorphisms (SNPs) were selected based on known or suspected function: AMHR2 rs2002555; CYP2C9*4 rs56165452; CYP2C19*2 rs4244285; and CYP2C19*3 rs4986893. SNPs were genotyped using TaqMan assays. Linear regression was used to determine the association between selected factors and AMH levels (log10[AMH+1]).
RESULTS: The mean age at LTSP enrollment was 12.4 years. The most common cancer diagnosis was acute lymphoblastic leukemia (47.2%), and a substantial proportion of the population was Hispanic (41.0%). The following variables were significantly associated with lower AMH levels: pelvic radiation (beta=-0.61, P<0.001) and treatment with alkylating agents (beta=-0.09, P=0.04). Enrollment age was associated with higher AMH levels (beta=0.01, P=0.04). Hispanic ethnicity was marginally associated with lower AMH levels (beta=-0.08, P=0.08). There were no significant genetic associations.
CONCLUSION: Our results confirm previous associations of treatment-related factors and ovarian damage, while suggesting a potential association between Hispanic ethnicity and ovarian damage. While the SNPs evaluated were not predictive of AMH levels, more work is needed to explain why some patients experience impaired fertility, while others do not, despite similar therapy.
