C77G in PTPRC (CD45) is no risk allele for ovarian cancer, but associated with less aggressive disease

• Published in: PloS one 2017-07, Vol.12 (7), p.e0182030-e0182030
• Main Authors: Landskron, Johannes, Kraggerud, Sigrid M, Wik, Elisabeth, Dørum, Anne, Bjørnslett, Merete, Melum, Espen, Helland, Øystein, Bjørge, Line, Lothe, Ragnhild A, Salvesen, Helga B, Taskén, Kjetil
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Alleles; Alternative splicing; Antigens; Autoimmune diseases; Biology and Life Sciences; Biomarkers; Cancer; Case-Control Studies; CD45 antigen; CD45RA antigen; Colorectal cancer; Diagnosis; Effector cells; Exons; Female; Gene expression; Gene Frequency; Genetics; Genomes; Gynecology; Health risks; Histology; Hospitals; Humans; Immunological memory; Immunology; Immunotherapy; Isoforms; Kinases; Leukocyte Common Antigens - genetics; Ligands (Biochemistry); Lymphocytes; Lymphocytes T; Medical diagnosis; Medical research; Medicine; Medicine and Health Sciences; Memory cells; Middle Aged; mRNA; Mutation; Mutation, Missense; Norway; Obstetrics; Oncology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Patients; People and Places; Phosphorylation; Polymorphism, Single Nucleotide; Proteins; Research and Analysis Methods; Single-nucleotide polymorphism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182030

The pan lymphocyte marker CD45 exists in various isoforms arising from alternative splicing of the exons 4, 5 and 6. While naïve T cells express CD45RA translated from an mRNA containing exon 4, exons 4-6 are spliced out to encode the shorter CD45R0 in antigen-experienced effector/memory T cells. The SNP C77G (rs17612648) is located in exon 4 and blocks the exon's differential splicing from the pre-mRNA, enforcing expression of CD45RA. Several studies have linked C77G to autoimmune diseases but lack of validation in other cohorts has left its role elusive. An incidental finding in an ovarian cancer patient cohort from West Norway (Bergen region, n = 312), suggested that the frequency of C77G was higher among ovarian cancer patients than in healthy Norwegians (n = 1,357) (3.0% vs. 1.8% allele frequency). However, this finding could not be validated in a larger patient cohort from South-East Norway (Oslo region, n = 1,198) with 1.2% allele frequency. Hence, C77G is not associated with ovarian cancer in the Norwegian population. However, its frequency was increased in patients with FIGO stage II, endometrioid histology or an age at diagnosis of 60 years or older indicating a possible association with a less aggressive cancer type.