title: Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population.
abstract: The concentration of the tumor marker CA 19-9 is influenced by the patient's secretor status and Lewis genotype. The aim of this study was to establish novel reference intervals for CA 19-9 in serum based on secretor and Lewis genotypes, to investigate the biological variation of CA 19-9, and to evaluate the utility of Lewis and secretor genotyping on a group of individuals with serologically defined Lewis phenotypes. CA 19-9 was measured in serum of 500 healthy individuals. Secretor and Lewis genotypes were determined by sequencing and PCR-cleavage methods. Significant differences were found between subgroups with different Lewis and secretor genotypes. Genotype-based reference intervals for CA 19-9 are presented. The upper reference limit for all individuals was 28.7 kilounits/L; for secretors and nonsecretors, the upper reference limits were 12.4 and 61.2 kilounits/L, respectively. The analytical imprecision (CVA) was 9.8%, the within-subject variability (CVI) was 15.8%, and the between-subject variability (CVG) was 102.2%. Good agreement was found between Lewis and secretor genotyping and conventional blood grouping. Genotype-based reference intervals may be a way to increase the clinical utility of CA 19-9. On the basis of the calculation of a critical difference for sequential values (significant at P </=0.05) of 51.5%, a 40-50% change in marker concentration is suggested as the limit for significant change when the marker is used for follow up. PCR-based genotyping is a reliable method for secretor and Lewis histo-blood grouping.
authors.affiliation: Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Denmark.
authors.forename: E M
authors.initials: EM
authors.lastname: Vestergaard
authors.forename: H O
authors.initials: HO
authors.lastname: Hein
authors.forename: H
authors.initials: H
authors.lastname: Meyer
authors.forename: N
authors.initials: N
authors.lastname: Grunnet
authors.forename: J
authors.initials: J
authors.lastname: Jørgensen
authors.forename: H
authors.initials: H
authors.lastname: Wolf
authors.forename: T F
authors.initials: TF
authors.lastname: Orntoft
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018395:CA-19-9 Antigen / Q000097:blood*; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D005838:Genotype; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044465:White People / Q000235:genetics*; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D005647:Fucosyltransferases; D007983:Lewis Blood Group Antigens; D000097631:Galactoside 2-alpha-L-fucosyltransferase