TAP1, TAP2, and HLA-DR2 alleles are predictors of cervical cancer risk.
OBJECTIVE
The likelihood of developing cervical cancer has been shown to be increased in persons with certain HLA alleles. We evaluated immune response genes in the HLA region of chromosome 6 to see if individual or interactive associations with cervical cancer risk could be identified.


METHODS
Tissue was obtained from 127 women undergoing surgical treatment for cervical cancer. Blood samples were obtained from 175 control subjects. A combination of polymerase chain reaction (PCR), sequence-specific PCR, and DNA sequencing was used to evaluate polymorphic alleles, including HLA class I B7, TNF alpha, HLA class II DR2, TAP1, and TAP2 genes. Fisher's exact test and logistic regression modeling were used for statistical analysis.


RESULTS
A significantly greater proportion of the patients with cervical cancer were found to have the HLA class II DR2 1501 allele (P = 0.023) and the TAP2 A/B heterozygous pattern of alleles (P = 0.0006) than were women without cervical cancer. A proportion of patients with cervical cancer significantly smaller than that of the control women had a polymorphism at the -238 position of the TNF promoter and the TAP1 C/C homozygous pattern of alleles. With logistic modeling, the markers that showed consistent association with the occurrence of cervical cancer were TAP2 A/B, HLA-DR2 1501, and TAP1 C/C.


CONCLUSIONS
We demonstrated a significant association between immune response genes and the risk of cervical cancer. Our data create a compelling argument for a gene or a cluster of genes in the HLA region of chromosome 6 that regulates host immune responses to human papillomavirus infection in a manner that results in inherited susceptibility or resistance to the transforming properties of oncogenic papillomaviruses.
Gostout
Bobbie S
BS
Section of Gynecologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. gostout.bobbie@mayo.edu
Poland
Gregory A
GA
Calhoun
Eric S
ES
Sohni
Youvraj R
YR
Giuntoli
Robert L
RL
McGovern
Renee M
RM
Sloan
Jeff A
JA
Cha
Stephen S
SS
Persing
David H
DH
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015793:HLA-B7 Antigen / Q000235:genetics; D015802:HLA-DR2 Antigen / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000145:classification; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015793:HLA-B7 Antigen; D015802:HLA-DR2 Antigen; C073119:TAP1 protein, human; D014409:Tumor Necrosis Factor-alpha; C071692:TAP2 protein, human