Genetic variants in TAP are associated with high-grade cervical neoplasia

Mark H. Einstein, Suzanne Leanza, Lydia G. Chiu, Nicolas F. Schlecht, Gary L. Goldberg, Bettie M. Steinberg, Robert D. Burk

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Purpose: The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms inTAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design: Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex xMAP). HPV typingwas done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results: Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (P = 0.01). The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions: In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer.

Original languageEnglish (US)
Pages (from-to)1019-1023
Number of pages5
JournalClinical Cancer Research
Volume15
Issue number3
DOIs
StatePublished - Feb 1 2009

Fingerprint

Cervical Intraepithelial Neoplasia
Neoplasms
Papillomavirus Infections
Odds Ratio
Single Nucleotide Polymorphism
Down-Regulation
Confidence Intervals
Proteins
Therapeutic Irrigation
Genetic Polymorphisms
Microspheres
Uterine Cervical Neoplasms
Case-Control Studies
Research Design
Alleles
Technology
Polymerase Chain Reaction
DNA
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Einstein, M. H., Leanza, S., Chiu, L. G., Schlecht, N. F., Goldberg, G. L., Steinberg, B. M., & Burk, R. D. (2009). Genetic variants in TAP are associated with high-grade cervical neoplasia. Clinical Cancer Research, 15(3), 1019-1023. https://doi.org/10.1158/1078-0432.CCR-08-1207

Genetic variants in TAP are associated with high-grade cervical neoplasia. / Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

In: Clinical Cancer Research, Vol. 15, No. 3, 01.02.2009, p. 1019-1023.

Research output: Contribution to journalArticle

Einstein, MH, Leanza, S, Chiu, LG, Schlecht, NF, Goldberg, GL, Steinberg, BM & Burk, RD 2009, 'Genetic variants in TAP are associated with high-grade cervical neoplasia', Clinical Cancer Research, vol. 15, no. 3, pp. 1019-1023. https://doi.org/10.1158/1078-0432.CCR-08-1207
Einstein MH, Leanza S, Chiu LG, Schlecht NF, Goldberg GL, Steinberg BM et al. Genetic variants in TAP are associated with high-grade cervical neoplasia. Clinical Cancer Research. 2009 Feb 1;15(3):1019-1023. https://doi.org/10.1158/1078-0432.CCR-08-1207
Einstein, Mark H. ; Leanza, Suzanne ; Chiu, Lydia G. ; Schlecht, Nicolas F. ; Goldberg, Gary L. ; Steinberg, Bettie M. ; Burk, Robert D. / Genetic variants in TAP are associated with high-grade cervical neoplasia. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 3. pp. 1019-1023.
@article{d593769504444cefbce5391e6c8b64f4,
title = "Genetic variants in TAP are associated with high-grade cervical neoplasia",
abstract = "Purpose: The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms inTAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design: Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex xMAP). HPV typingwas done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results: Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (P = 0.01). The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95{\%} confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95{\%} confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions: In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer.",
author = "Einstein, {Mark H.} and Suzanne Leanza and Chiu, {Lydia G.} and Schlecht, {Nicolas F.} and Goldberg, {Gary L.} and Steinberg, {Bettie M.} and Burk, {Robert D.}",
year = "2009",
month = "2",
day = "1",
doi = "10.1158/1078-0432.CCR-08-1207",
language = "English (US)",
volume = "15",
pages = "1019--1023",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Genetic variants in TAP are associated with high-grade cervical neoplasia

AU - Einstein, Mark H.

AU - Leanza, Suzanne

AU - Chiu, Lydia G.

AU - Schlecht, Nicolas F.

AU - Goldberg, Gary L.

AU - Steinberg, Bettie M.

AU - Burk, Robert D.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - Purpose: The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms inTAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design: Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex xMAP). HPV typingwas done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results: Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (P = 0.01). The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions: In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer.

AB - Purpose: The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms inTAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design: Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex xMAP). HPV typingwas done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results: Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (P = 0.01). The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions: In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer.

UR - http://www.scopus.com/inward/record.url?scp=61349118779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349118779&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-1207

DO - 10.1158/1078-0432.CCR-08-1207

M3 - Article

C2 - 19188174

AN - SCOPUS:61349118779

VL - 15

SP - 1019

EP - 1023

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 3

ER -