Planning for individualized cancer screening programs

see Incorporating genomics into breast and prostate cancer screening: assessing the implications and How can polygenic inheritance be used in population screening for common diseases?

We justify public health screening for cancer by estimating that the benefits of public surveillance outweigh the attendant risks, which include false-positive test results and its associated psychological stress. Public acceptance of and participation in screening programs relies on trust and perceived benefit. Genomically informed screening aims to provide an individualized risk profile that incorporates genomic risk and demographic features to influence how and when each person should be screened. In this issue, Chowdhury et al. examine the ramifications of population-based genomic risk stratification. The authors present the recommendations from a series of workshops convened in 2010 and 2011 by the Foundation for Genomics and Population Health and the University of Cambridge. Genomic information, they explain, could help triage individuals into new risk categories that include genetic risk when determining the appropriate level of cancer screening, including the possibility of earlier screening for those at highest risk and less frequent screening for those at lowest risk. The authors suggest that more personalized communication of risk information may help increase the use of existing screening methods. However, they stress that acquiring and using personal genetic information as part of a population-based screening program will inevitably result in concerns about discrimination and stigmatization.

In an accompanying Special Article, Khoury et al. suggest that our current knowledge of genetic risk for common diseases is insufficient to justify screening in most cases. In the case of colorectal cancer screening, however, they suggest that awareness of genetic risk factors may provide better risk information than family history alone. They also stress that it is unclear whether genetic risk stratification will help distinguish life-threatening cancers from milder manifestations, an ongoing concern with current screening programs. —Karyn Hede, News Editor

Karyotyping remains useful in our genomic realm

see Comparison of chromosome analysis and chromosomal microarray analysis: what is the value of chromosome analysis in today’s genomic array era?

Visual inspection of chromosomes has been a mainstay of genetic diagnosis since the 1960s, when the advent of standardized staining techniques enabled routine identification of chromosomal abnormalities. The ACMG’s recommendation of chromosomal microarray analysis (CMA) as a first-tier diagnostic test for congenital developmental disorders has led some to question the continuing value of classic karyotyping procedures. Bi et al. provide data showing that classic chromosome analysis remains valuable as a second-tier or confirmatory technique for detecting mosaicism and fine mapping of chromosomal structural rearrangements. The authors identified 3,710 cases in which both traditional chromosome analysis and CMA were performed in a clinical setting. Chromosome analysis detected abnormalities in 295 cases (8%); CMA failed to identify the abnormalities in 10 of these cases. Retesting by CMA correctly identified the abnormalities in 4 of the 10 cases. The remaining missed diagnoses involved subtle mosaicism. For patients with normal CMA results, a full chromosome analysis may be warranted if the individual has multiple congenital anomalies that suggest a chromosomal syndrome. —Karyn Hede, News Editor