Association between DQB1 and cervical cancer in patients with human papillomavirus and family controls.
OBJECTIVE
The role of human leukocyte antigen (HLA) DQB1 alleles and human papillomavirus (HPV) as contributing factors to invasive cervical cancer was investigated. To overcome problems of misleading causal inferences common in traditional case-control studies, a family-based test, the transmission/disequilibrium test, was used.


METHODS
Ninety-six patients with pathologically confirmed invasive cervical cancer were ascertained. Human papillomavirus types were determined in 80 patients, of whom 81.25% were HPV-positive, and 18.75% were HPV-negative. Deoxyribonucleic acid was extracted from samples, taken from patients and their parents, and sequenced to determine DQB1 genotypes. Nuclear family data were used to test whether the DQB1 locus is associated with invasive cervical cancer while controlling for high-risk HPV-positive patients. The transmission/disequilibrium test evaluates whether the frequency of transmission of parental marker alleles to their affected offspring deviates from the expected Mendelian frequency of 50%.


RESULTS
The HLA DQB1 locus showed evidence for allelic association with invasive cervical cancer in high-risk HPV-positive patients (P = .006). The transmission/disequilibrium test showed that the DQB1*0303 allele was transmitted to high-risk HPV patients more often than expected by chance, chi2(1) = 8.0, P = .005 (P = .035 when correcting for multiple tests). Tests of association were negative when applied to all 96 patients, irrespective of HPV status. No significant differences were found in the distribution of the DQB1 alleles among HPV-positive patients compared with those who were HPV-negative, indicating that HLA alleles are not associated with susceptibility to HPV infection.


CONCLUSIONS
These results suggest that the DQB1*0303 allele increases the risk for invasive cervical cancer in women who are HPV-positive.
Neuman
R J
RJ
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA. roz@gretta.wustl.edu
Huettner
P C
PC
Li
L
L
Mardis
E R
ER
Duffy
B F
BF
Wilson
R K
RK
Rader
J S
JS
D000230:Adenocarcinoma / Q000235:genetics / Q000821:virology; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000821:virology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications*; D014412:Tumor Virus Infections / Q000150:complications*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology*
D006683:HLA-DQ Antigens