The psychological impact of genetic testing in childhood cancer: A systematic review.

OBJECTIVE: Cancer predisposition syndromes are being more frequently recognized in the etiology of pediatric oncology and genetic-related technologies are evolving rapidly, leading to an increasing availability of genetic testing for families. This systematic review assessed the psychological impact of genetic testing on children and parents in the context of childhood cancer. METHODS: Searches were performed using three databases (Web of Science, Pubmed and Embase) to identify relevant empirical studies. Following Cochrane guidelines, we screened 3838 articles and identified 18 eligible studies, representing the perspectives of children and/or parents. RESULTS: The included studies described the impact of genetic testing in different contexts (e.g. predictive testing and diagnostic testing) and in different subgroups, (e.g. carriers and non-carriers). Overall, the studies did not identify clinically-relevant long-term increases in negative emotions (depression, anxiety, distress, uncertainty, guilt) as a result of genetic testing. Negative emotions were typically time-limited and generally occurred in families with particular characteristics (e.g. those with a history of multiple cancer diagnoses, families receiving an unfavorable result for one child and a favorable result in siblings, and those with pre-existing mental health difficulties). Positive emotions (hopefulness, relief and peace of mind) were also reported. Knowing their genetic risk status appeared to help to foster empowerment among families, regardless of the result and any associated emotions. CONCLUSIONS: Genetic testing in pediatric oncology does not appear to cause significant additional harm and can lead to positive outcomes. Clinicians need to be especially attentive when counseling families at increased risk of distress.

Joint Belgian recommendation on screening for DPD-deficiency in patients treated with 5-FU, capecitabine (and tegafur).

OBJECTIVES: Fluoropyrimidines such as 5-Fluorouracil (5-FU), capecitabine and tegafur are drugs that are often used in the treatment of maliginancies. The enzyme dihydropyrimidine dehydrogenase (DPD) is the first and rate limiting enzyme of 5-FU catabolism. Genetic variations within the DPYD gene (encoding for DPD protein) can lead to reduced or absent DPD activity. Treatment of DPD deficient patients with fluoropyrimidines can result in severe and, rarely, fatal toxicity. Screening for DPD deficiency should be implemented in practice. METHODS: The available methods in routine to screen for DPD deficiency were analyzed and discussed in several group meetings involving members of the oncological, genetic and toxicological societies in Belgium: targeted genotyping based on the detection of 4 DPYD variants and phenotyping, through the measurement of uracil and dihydrouracil/uracil ratio in plasma samples. RESULTS: The main advantage of targeted genotyping is the existence of prospectively validated genotype-based dosing guidelines. The main limitations of this approach are the relatively low sensitivity to detect total and partial DPD deficiency and the fact that this approach has only been validated in Caucasians so far. Phenotyping has a better sensitivity to detect total and partial DPD deficiency when performed in the correct analytical conditions and is not dependent on the ethnic origin of the patient. CONCLUSION: In Belgium, we recommend phenotype or targeted genotype testing for DPD deficiency before starting 5-FU, capecitabine or tegafur. We strongly suggest a stepwise approach using phenotype testing upfront because of the higher sensitivity and the lower cost to society.