Knowledge of carrier status low among relatives of CF patients

see Cascade carrier testing after a child is diagnosed with cystic fibrosis through newborn screening: investigating why most relatives do not have testing

Diagnosis of a newborn with cystic fibrosis (CF) has consequences not only for the parents but also for the extended family. With a carrier frequency of 1 in 25, the CF mutation is the most common serious recessive condition among northern Europeans. After diagnosis, parents face issues with regard to informing family members about their increased risk of being a carrier. Little is known about how these conversations affect the subsequent decision by relatives as to whether to be tested for carrier status. McClaren et al. studied this communication process and decisions regarding testing among a population of patients at Royal Children’s Hospital in Melbourne, Australia. Parents of newly diagnosed children were counseled about the implications for immediate-family members and were provided with a sample letter to assist in communicating the information. Despite these efforts, only 11.8% of relatives accessed the free carrier testing available at the hospital. Follow-up interviews with parents and extended family of 30 newly diagnosed children revealed that notification was uneven and depended on personal relationships among family members. Parents reported that they were comfortable with their own understanding of the genetic cause and inheritance of CF but that they felt the concepts were difficult for their relatives to understand. The study’s results indicated that relatives outside the immediate family were less likely to have been tested. The authors suggest that, after a period of adjustment, additional contact by health-care providers with parents to discuss implications for relatives might be useful in increasing family members’ knowledge. —Karyn Hede, News Editor

KRAS testing in metastatic colorectal cancer patients

see Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

Colorectal cancer tumors that harbor specific mutations affecting epidermal growth factor receptor (EGFR) pathway signaling have been shown to be generally unresponsive to therapy with anti-EGFR antibodies such as cetuximab and panitumumab. The Evaluation of Genomic Applications in Practice and Prevention Working Group recently reviewed the evidence in order to determine the implications of these observations and concluded that clinical use of KRAS mutation analysis is warranted for metastatic colorectal cancer patients (the recommendation statement appears in full in this issue). The group concluded that analyses to identify those who are KRAS-mutation-positive would benefit patients by avoiding potentially ineffective and harmful treatment. Another conclusion is that, whereas there are convincing data to support KRAS-mutation testing, there is inadequate evidence that testing for the BRAF V600E mutation or loss of PTEN expression improves health outcomes. Nor was evidence found of improved health outcomes among those tested for NRAS or PIK3CA variants or AKT protein expression levels in this patient group. The working group’s recommendations include consideration of the fact that eliminating anti-EGFR therapy as an option following a positive test for KRAS mutation may promote quicker access to potentially more effective treatment. —Karyn Hede, News Editor