title: 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.affiliation: Department of Obstetrics and Gynecology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Maeda
authors.affiliation: Department of Obstetrics and Gynecology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Oki
authors.affiliation: Department of Health Economics, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Takatsuka
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasugi
authors.affiliation: Department of Pathology, Cancer Institute, Japanese Foundation of Cancer Research, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Furuta
authors.affiliation: Department of Transfusion Medicine and Cell Therapy, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: Ranko
authors.initials: R
authors.lastname: Hirata
authors.affiliation: Department of Reproductive Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mitsuhashi
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Departments of Gynecology and Cytopathology, Cancer Institute Hospital, Japanese Foundation of Cancer Research, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Obstetrics and Gynecology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.affiliation: Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Department of Obstetrics and Gynecology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People; D063646:Carcinogenesis / Q000235:genetics*; D003430:Cross-Sectional Studies; D060467:Disease Resistance / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007564:Japan; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000254:growth & development; D011446:Prospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D059811:HLA-DRB1 Chains
keywords: cervical cancer; cervical intraepithelial neoplasia; human leukocyte antigen; human papillomavirus; low-grade squamous intraepithelial lesion