Search

Summary: Background: Early maternal cancer and fertility treatment each increase the risk for adverse birth outcomes, but the joint effect of these outcomes has not yet been reported. Thus, the aim was to assess the individual and joint effect of maternal cancer and fertility treatment on the risk for adverse birth outcomes. Methods: This population-based cohort study included 5487 live-born singletons identified in the Danish Medical Birth Register (1994–2016) of mothers with previous cancer (

Purpose: Due to limited data on treatment-related risk factors associated with esophageal stricture in childhood cancer survivors, this study aimed to assess such factors in long-term survivors. Methods: A case-cohort study was conducted involving 36 cases of five-year childhood cancer survivors with esophageal stricture and a sub-cohort of 540 survivors diagnosed with cancer in 1970–2007 as identified within the Nordic ‘Adult Life after Childhood Cancer in Scandinavia’ program. Individualized treatment details were retrieved from medical records. Radiation doses to each body region and average dose to the esophagus were reconstructed for patients that received radiotherapy. We used a modified Cox proportional hazard model to evaluate associations between esophageal stricture and risk factors by calculating incidence rate ratio (IRR), with 95 % confidence intervals (CIs). Results: An increased rate of esophageal stricture was found in survivors who received total body irradiation (IRR=13.7, 95 %CI 4.6–41.1), chest- and neck-directed radiotherapy (IRR=23.5, 95 %CI 8.5−64.7) and doses of ≥12 Gy to the esophagus (IRR=26.8, 95 % CI=9.0–80.3) compared to non-irradiated survivors. Treatment with chemotherapy was also associated with esophageal stricture (IRR=8.4, 95 % CI=2.9–24.4). Notably, leukemia survivors faced an elevated rate (IRR=3.8, 95 % CI 1.8–8.1) compared with survivors of CNS and other solid tumors. Conclusions: Our findings indicate an increased risk of esophageal stricture among childhood cancer survivors, with both neck- and chest-directed radiotherapy and chemotherapy as important risk factors.

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patients were assigned to three phenotype categories: no, minor, and clinically relevant hearing loss. Fourteen variants in eleven candidate genes (ABCC3, OTOS, TPMT, SLC22A2, NFE2L2, SLC16A5, LRP2, GSTP1, SOD2, WFS1, and ACYP2) were genotyped. The genotype and phenotype data represent a resource for conducting meta-analyses to derive a more precise pooled estimate of the effects of genes on the risk of hearing loss due to platinum treatment.