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J Med Genet 2005;42:e49 doi:10.1136/jmg.2005.031351
  • Electronic letters

Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study

  1. M Zoodsma1,
  2. I M Nolte2,
  3. M Schipper2,
  4. E Oosterom2,
  5. G van der Steege2,
  6. E G E de Vries3,
  7. G J te Meerman4,
  8. A G J van der Zee1
  1. 1Department of Gynaecology, University Medical Centre Groningen, Groningen, Netherlands
  2. 2Department of Medical Biology, University Medical Centre Groningen
  3. 3Department of Medical Oncology, University Medical Centre Groningen
  4. 4Department of Medical Genetics, University Medical Centre Groningen
  1. Correspondence to:
 Professor A G J van der Zee
 Department of Gynaecology, Groningen University Medical Centre, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, Netherlands; A.G.J.van.der.zeeog.umcg.nl
  • Received 7 March 2005
  • Accepted 14 April 2005
  • Revised 12 April 2005

Abstract

Background: Infection with human papillomavirus (HPV) is the main cause of cervical cancer and its precursor lesion, cervical intraepithelial neoplasia (CIN). Variability in host immunogenetic background is important in determining the overall cellular immune response to HPV infections.

Objective: To determine whether the HLA-DQ or HLA-DR genes, or others in their vicinity, are associated with cervical cancer.

Methods: Markers covering the entire HLA region were genotyped in a large sample of CIN and cervical cancer patients and in controls (311 CIN, 695 cervical cancer, 115 family controls, and 586 unrelated controls).

Results: Two markers were associated with susceptibility to cervical neoplasia, G511525 and MICA. G511525, close to the region containing the HLA-DQ and HLA-DR genes, was most strongly associated, showing a decrease in frequency of allele 221 from 6.7% to 3.3% in patients with squamous cell cancer (SCC). An association was found for MICA (allele 184) with SCC (odds ratio (OR) = 1.31 (95% confidence interval, 1.13 to 1.53); homozygotes, OR = 1.48 (1.06 to 2.06)). No associations were observed with adenocarcinoma or CIN.

Conclusions: There is an association of the region containing the HLA-DQ and HLA-DR genes with the risk of developing squamous cell carcinoma. An increased risk was observed for carriers of allele 184 at the MICA locus, in particular for homozygotes, suggesting a recessive effect.

Footnotes

  • Competing interests: none declared

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