Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

Abstract

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ(2) -test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low-grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.

• Authors: Koji Matsumoto, Hiroo Maeda, Akinori Oki, Naoyoshi Takatsuka, Toshiharu Yasugi, Reiko Furuta, Ranko Hirata, Akira Mitsuhashi, Kei Kawana, Takuma Fujii, Takashi Iwata, Yasuo Hirai, Masatoshi Yokoyama, Nobuo Yaegashi, Yoh Watanabe, Yutaka Nagai, Hiroyuki Yoshikawa, Japan HPV and Cervical Cancer (JHACC) Study Group
• Journal: Cancer science (Cancer Sci) Vol. 106 Issue 10 Pg. 1448-54 (Oct 2015) ISSN: 1349-7006 [Electronic] England
• PMID: 26235935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• HLA-DRB1 Chains

Topics

• Adolescent
• Adult
• Asian People
• Carcinogenesis (genetics)
• Cross-Sectional Studies
• Disease Resistance (genetics)
• Female
• Gene Frequency
• HLA-DRB1 Chains (genetics)
• Humans
• Japan
• Neoplasm Grading
• Papillomaviridae (growth & development)
• Prospective Studies
• Uterine Cervical Neoplasms (genetics, pathology, virology)
• Young Adult
• Uterine Cervical Dysplasia (genetics, pathology, virology)