Analysis of the entire HLA region in susceptibility for cervical cancer: a comprehensive study.
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.
Zoodsma
M
M
Nolte
I M
IM
Schipper
M
M
Oosterom
E
E
van der Steege
G
G
de Vries
E G E
EG
te Meerman
G J
GJ
van der Zee
A G J
AG
D000230:Adenocarcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics
D005819:Genetic Markers; D006680:HLA Antigens