[Biomarkers collections: the future or a waste of resources?]. / Biomarkersammlungen: Zukunft oder Ressourcenverschwendung?

Disease biomarkers would aim at a more specific definition of diagnosis or subtype of a certain disease, as well as prognosis definition, including efficacy and side effects of certain therapeutics. Biomarkers could lead to a prognostically optimized definition of remission in the individual patient and thus to a more objective definition of therapeutic efficacy. Is this possible and does it make sense? Or would an extensive analysis of biomarkers to date lead to a costly overestimation of as yet not well established biologic parameters? Although we are currently unable to answer this question, many colleagues argue in favour of more in depth research for a better evaluation of biomarkers in many diseases. This could save money if we were able to predict the efficacy of expensive drugs such as immunobiologics. Biomarkers comprise cytometric information, data on protein expression and secretion, mRNA, microRNA or DNA, including epigenetic variants. Although much of these data already exist in the scientific literature, it is associated with problems in terms of feasibility (for cytometry and RNA analysis only on-site analysis is possible, while for DNA analysis central testing is also possible), costs and reproducibility (ethnic variability!). To date all biomarkers have only limited value in terms of the above-mentioned aims. The present review compiles "PROs and CONs" in a subjective way in order to provoke a discussion on the meaningfulness of biomarkers, while at the same time supporting and encouraging further research in this field.

Ethical considerations in testing workers for the -Glu69 marker of genetic susceptibility to chronic beryllium disease.

OBJECTIVE: The most compelling real-world example of genetic testing for susceptibility to a workplace exposure involves those industries that process or fabricate beryllium. We examined ethical issues associated with testing for susceptibility to chronic beryllium disease. METHODS: Using ethical and clinical criteria, we examined voluntary employer-sponsored testing programs in which individual results are reported directly to workers in a confidential manner. RESULTS: Under reasonable assumptions, the longitudinal positive predictive value of the HLA-DPB1-Glu69 marker of susceptibility to beryllium disease is 12%. Interpretive challenges further limit the utility of the test and may inadvertently suggest a false sense of safety among workers. Concerns about confidential participation and pressures to be tested also must be addressed. CONCLUSIONS: Difficulties surrounding the interpretation of the HLA-DPB1-Glu69 marker, lack of assurance regarding the protection of worker confidentiality, and the potential lowering of social barriers to the implementation of mandatory worker screening combine to make testing beryllium workers inappropriate at this time.

The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer.

Breast development, one of the first signs of puberty, is closely associated with age at menarche; and early menarche is in turn a well-established risk factor for female breast cancer. We examined the relationships between the onset of puberty and gene variants for certain enzymes that regulate hormone metabolism among 137 healthy nine-year-old girls from two pediatric clinics. High-activity CYP17 alleles, involved in estrogen formation, and high-activity CYP1A2 and CYP1B1 alleles, whose gene products metabolize estradiol, were not associated with pubertal stage. High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Of the homozygous CYP3A4*1B/1B girls, 90% had reached puberty; whereas, for the low-activity homozygous CYP3A4*1A/1A individuals, only 40% had done so. In heterozygotes, 56% had reached puberty. CYP1B1, CYP3A4, and CYP3A5 rapid variants were more common in African-American than in Hispanic or Caucasian girls.