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Gynecol Oncol. 2003 Mar;88(3):326-32.

TAP1, TAP2, and HLA-DR2 alleles are predictors of cervical cancer risk.

Author information

  • 1Section of Gynecologic Surgery, Mayo Clinic, Rochester, MN 55905, USA. gostout.bobbie@mayo.edu

Abstract

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.

PMID:
12648582
[PubMed - indexed for MEDLINE]
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