Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer

At which step of multistage carcinogenesis?

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 χ2-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.

Original languageEnglish
JournalCancer Science
DOIs
Publication statusAccepted/In press - 2015

Fingerprint

HLA Antigens
Uterine Cervical Neoplasms
Carcinogenesis
Alleles
Cell Biology
Gene Frequency
Colposcopy
Cervical Intraepithelial Neoplasia
Cross-Sectional Studies
Squamous Intraepithelial Lesions of the Cervix

Keywords

  • Cervical cancer
  • Cervical intraepithelial neoplasia
  • Human leukocyte antigen
  • Human papillomavirus
  • Low-grade squamous intraepithelial lesion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Matsumoto, K., Maeda, H., Oki, A., Takatsuka, N., Yasugi, T., Furuta, R., ... Yoshikawa, H. (Accepted/In press). Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis? Cancer Science. https://doi.org/10.1111/cas.12760

Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer : At which step of multistage carcinogenesis? / Matsumoto, Koji; Maeda, Hiroo; Oki, Akinori; Takatsuka, Naoyoshi; Yasugi, Toshiharu; Furuta, Reiko; Hirata, Ranko; Mitsuhashi, Akira; Kawana, Kei; Fujii, Takuma; Iwata, Takashi; Hirai, Yasuo; Yokoyama, Masatoshi; Yaegashi, Nobuo; Watanabe, Yoh; Nagai, Yutaka; Yoshikawa, Hiroyuki.

In: Cancer Science, 2015.

Research output: Contribution to journalArticle

Matsumoto, K, Maeda, H, Oki, A, Takatsuka, N, Yasugi, T, Furuta, R, Hirata, R, Mitsuhashi, A, Kawana, K, Fujii, T, Iwata, T, Hirai, Y, Yokoyama, M, Yaegashi, N, Watanabe, Y, Nagai, Y & Yoshikawa, H 2015, 'Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?', Cancer Science. https://doi.org/10.1111/cas.12760
Matsumoto, Koji ; Maeda, Hiroo ; Oki, Akinori ; Takatsuka, Naoyoshi ; Yasugi, Toshiharu ; Furuta, Reiko ; Hirata, Ranko ; Mitsuhashi, Akira ; Kawana, Kei ; Fujii, Takuma ; Iwata, Takashi ; Hirai, Yasuo ; Yokoyama, Masatoshi ; Yaegashi, Nobuo ; Watanabe, Yoh ; Nagai, Yutaka ; Yoshikawa, Hiroyuki. / Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer : At which step of multistage carcinogenesis?. In: Cancer Science. 2015.
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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 χ2-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.",
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AU - Matsumoto, Koji

AU - Maeda, Hiroo

AU - Oki, Akinori

AU - Takatsuka, Naoyoshi

AU - Yasugi, Toshiharu

AU - Furuta, Reiko

AU - Hirata, Ranko

AU - Mitsuhashi, Akira

AU - Kawana, Kei

AU - Fujii, Takuma

AU - Iwata, Takashi

AU - Hirai, Yasuo

AU - Yokoyama, Masatoshi

AU - Yaegashi, Nobuo

AU - Watanabe, Yoh

AU - Nagai, Yutaka

AU - Yoshikawa, Hiroyuki

PY - 2015

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N2 - 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 χ2-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.

AB - 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 χ2-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.

KW - Cervical cancer

KW - Cervical intraepithelial neoplasia

KW - Human leukocyte antigen

KW - Human papillomavirus

KW - Low-grade squamous intraepithelial lesion

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