Costs and effects of genetic screening with application to cystic fibrosis and fragile X syndrome

Two to six percent of all newborn children have a disorder with a genetic cause (1-3). For an increasing number of these diseases, the precise genetic cause is known and this can lead to new treatment opportunities (see Appendix A for a basic description of the mechanisms of genetic inheritance). However, for most disorders total cure is not yet possible. For example, complications in patients with cystic fibrosis can be reduced by intensive treatment, but many patients will still die of lung problems caused by the disease. For diseases for which cure is not yet possible genetic screening might be a (temporary) solution. For example, a genetic screening programme in most Western countries is the offer of amniocentesis to pregnant women of a specified age (36 years and older in The Netherlands) to detect Down syndrome. Women in whom a foetus with Down syndrome is detected can then decide to prepare for the birth of an affected child or to avoid its birth by induced abortion. A list with examples of tests to detect disorders with a genetic cause or component currently offered in The Netherlands is given in Table 1.1. Because of the increasing number of genetic diseases that can be detected early, this list will probably continue to be extended

Comparison of two assays for human kallikrein 2

BACKGROUND: We compared two recently developed research assays for the measurement of human kallikrein 2 (hK2) in serum: one fully automated assay (Beckman Coulter Access immunoanalyzer) and one manual assay based on the DELFIA technology. METHODS: We used two subsets of clinical specimens consisting of 48 samples from prostate cancer patients and 210 samples from participants in an ongoing screening study (ERSPC). Both subsets were measured in the Rotterdam laboratory, and the prostate cancer samples were used for analytical comparison with the originating sites for the assays: Beckman Coulter Research Department (San Diego, CA) and Turku University (Turku, Finland). RESULTS: Both the Beckman Coulter and the Turku assays performed very similarly between the Rotterdam laboratory and the originating sites: the R(2) value for both comparisons was 0.99, and the slope difference between sites was <20%. Deming regression analysis of the DELFIA (y) and Access (x) assays yielded the following: for the prostate cancer group, y = 1.17x - 0.01 (R(2) = 0.88; n = 48); and for the ERSPC group, y = 0.62x - 0.01 (R(2) = 0.77). Breakdown of the latter group into subgroups (nondiseased, benign prostatic hyperplasia, and prostate cancer samples) gave only minor differences. The Access calibrators were underrecovered by 13% in the DELFIA assay, whereas the DELFIA calibrators were overrecovered by 45% in the Access assay. CONCLUSION: The DELFIA and Access assays for hK2, which have similar analytical features, show differences that cannot be explained by calibration

Molecular cytogenetic analysis of prostatic adenocarcinomas from screening studies : early cancers may contain aggressive genetic features

No objective parameters have been found so far that can predict the biological behavior of early stages of prostatic cancer, which are encountered frequently nowadays due to surveillance and screening programs. We have applied comparative genomic hybridization to routinely processed, paraffin-embedded radical prostatectomy specimens derived from patients who participated in the European Randomized Study of Screening for Prostate Cancer. We defined a panel consisting of 36 early cancer specimens: 13 small (total tumor volume (Tv) < 0.5 ml) carcinomas and 23 intermediate (Tv between 0.5-1.0 ml) tumors. These samples were compared with a set of 16 locally advanced, large (Tv > 2.0 ml) tumor samples, not derived from the European Randomized Study of Screening for Prostate Cancer. Chromosome arms that frequently (ie, > or = 15%) showed loss in the small tumors included 13q (31%), 6q (23%), and Y (15%), whereas frequent (ie, > or = 15%) gain was seen of 20q (15%). In the intermediate cancers, loss was detected of 8p (35%), 16q (30%), 5q (26%), Y (22%), 6q, and 18q (both 17%). No consistent gains were found i