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

PLoS One. 2017 Jul 31;12(7):e0182030. doi: 10.1371/journal.pone.0182030. eCollection 2017.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Humans
  • Leukocyte Common Antigens / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Norway
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Polymorphism, Single Nucleotide

Substances

  • Leukocyte Common Antigens
  • PTPRC protein, human

Grant support

This work was supported by the Research Council of Norway, http://www.forskningsradet.no, 187615 (KT), 179571 (SMK and RAL); The Norwegian Cancer Society, https://kreftforeningen.no/en/main-priorities/, 419544 (KT); The South-Eastern Norway Regional Health Authority, https://www.helse-sorost.no/, 2015031 (KT); The Western Norway Regional Health Authority, https://helse-vest.no/, (LB and HBS) and K. G. Jebsen Foundation, http://www.stiftkgj.no/, (JL and KT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.