RT Journal Article
SR Electronic
T1 Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP e49
OP e49
DO 10.1136/jmg.2005.031351
VO 42
IS 8
A1 M Zoodsma
A1 I M Nolte
A1 M Schipper
A1 E Oosterom
A1 G van der Steege
A1 E G E de Vries
A1 G J te Meerman
A1 A G J van der Zee
YR 2005
UL http://jmg.bmj.com/content/42/8/e49.abstract
AB 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.