Analysis of Erythrocyte Glycophorin-A Variants by Flow Cytometry in Lung Disease Patients Detects the Effect of Tobacco Smoke

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment. GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The N0 and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies. We explored if GPA N0 and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non‐malignant lung diseases associated with increased risk of lung cancer. There was a wide interindividual variability and complete overlap between non‐neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in N0 VF (p=0.04, age‐adjusted). Current smokers (n=12) displayed higher N0 values than never (n=1) or ex‐smokers (n=11), 36.3±18.2 and 21.0±13.2, respectively (p < 0:01). No association was shown with occupational exposure. The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

[1]  D. Hanahan,et al.  The Hallmarks of Cancer , 2000, Cell.

[2]  S. Mayne,et al.  Previous lung disease and risk of lung cancer among men and women nonsmokers. , 1999, American journal of epidemiology.

[3]  V. Saenko,et al.  Determination of somatic mutant frequencies at glycophorin A and T-cell receptor loci for biodosimetry of prolonged irradiation. , 1998, International journal of radiation biology.

[4]  A. Auvinen,et al.  Biodosimetry of Chernobyl cleanup workers from Estonia and Latvia using the glycophorin A in vivo somatic cell mutation assay. , 1997, Radiation research.

[5]  K. Wakabayashi,et al.  Evidence for increased somatic cell mutations in patients with hepatocellular carcinoma. , 1997, Carcinogenesis.

[6]  R J Albertini,et al.  Somatic cell mutations in cancer epidemiology. , 1997, IARC scientific publications.

[7]  H. Norppa,et al.  Glycophorin A somatic cell mutation frequencies in Finnish reinforced plastics workers exposed to styrene. , 1996, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[8]  W. Börner,et al.  Improved determination of variant erythrocytes at the glycophorin A (GPA) locus and variant frequency in patients treated with radioiodine for thyroid cancer. , 1996, International journal of radiation biology.

[9]  A. Awa,et al.  Somatic cell mutations at the glycophorin A locus in erythrocytes of atomic bomb survivors: implications for radiation carcinogenesis. , 1996, Radiation research.

[10]  W. Bigbee,et al.  Direct immunofluorescence labeling provides an improved method for the glycophorin A somatic cell mutation assay. , 1996, Cytometry.

[11]  J. Boyse,et al.  Glycophorin A mutations and risk of secondary leukaemia in patients treated for childhood acute lymphoblastic leukaemia , 1996, British journal of haematology.

[12]  B. Henderson,et al.  Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States. , 1995, American journal of epidemiology.

[13]  Y. Ishikawa,et al.  Somatic-cell mutations as a possible predictor of cancer risk. , 1995, Health physics.

[14]  W. Bigbee,et al.  Bone marrow somatic mutation after genotoxic cancer therapy , 1994, The Lancet.

[15]  J. Boyse,et al.  Do mutations at the glycophorin A locus i patients treated for childhood Hodgkin's disease predict secondary leukaemia? , 1994, The Lancet.

[16]  T. Skopek,et al.  International Commission for Protection Against Environmental Mutagens and Carcinogens. Working paper no. 3. Somatic mutant frequency, mutation rates and mutational spectra in the human population in vivo. , 1994, Mutation research.

[17]  S G Grant,et al.  In vivo somatic mutation and segregation at the human glycophorin A (GPA) locus: phenotypic variation encompassing both gene-specific and chromosomal mechanisms. , 1993, Mutation research.

[18]  F. Perera,et al.  HPRT and glycophorin A mutations in foundry workers: relationship to PAH exposure and to PAH-DNA adducts. , 1993, Carcinogenesis.

[19]  S. Rappaport,et al.  Use of the glycophorin A human mutation assay to study workers exposed to styrene. , 1993, Environmental health perspectives.

[20]  Multiple biological markers in germ cell tumor patients treated with platinum-based chemotherapy. , 1992, Cancer research.

[21]  Stephen G. Grant,et al.  Laser-based flow cytometric analysis of genotoxicity of humans exposed to ionizing radiation during the Chernobyl accident , 1991, Other Conferences.

[22]  A. Wyrobek,et al.  The effect of chemotherapy on the in vivo frequency of glycophorin A 'null' variant erythrocytes. , 1990, Mutation research.

[23]  W. Bigbee,et al.  An improved flow cytometric assay for somatic mutations at the glycophorin A locus in humans. , 1990, Cytometry.

[24]  W. Bigbee,et al.  Evidence for an elevated frequency of in vivo somatic cell mutations in ataxia telangiectasia. , 1989, American journal of human genetics.

[25]  C. Mountain,et al.  A new international staging system for lung cancer. , 1987, Chest.

[26]  W. Bigbee,et al.  Determination of somatic mutations in human erythrocytes by flow cytometry. , 1986, Progress in clinical and biological research.

[27]  O. Auerbach.  Histological Typing Of Lung Tumors , 1968 .