Genome-wide association study of cervical cancer suggests a role forARRDC3gene in human papillomavirus infection
| Autor: | Sana Yokoi, Dong Hang, Yongyong Shi, Atsushi Takahashi, Seiichiro Mori, Zhibin Hu, Fumihiko Takeuchi, Ding Ma, Zhiqiang Li, Keitaro Matsuo, Michiaki Kubo, Iwao Kukimoto, Fumihiko Matsuda, Ni Li, Peng Wu, Yoichiro Kamatani, Shuang Li, Jianhua Chen, Mika Mizuno, Naotake Tanaka, Shusaku Inoue, Makoto Kuroda |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Arrestins Uterine Cervical Neoplasms Single-nucleotide polymorphism Genome-wide association study Human leukocyte antigen Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Asian People Genetics medicine Humans SNP Genetic Predisposition to Disease Papillomaviridae Molecular Biology Genetics (clinical) Genetic association Cervical cancer biology Papillomavirus Infections HPV infection General Medicine medicine.disease biology.organism_classification 030104 developmental biology 030220 oncology & carcinogenesis Female Genome-Wide Association Study HeLa Cells |
| Zdroj: | Human Molecular Genetics. 28:341-348 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddy390 |
| Popis: | The development of cervical cancer is initiated by human papillomavirus (HPV) infection and involves both viral and host genetic factors. Genome-wide association studies (GWAS) of cervical cancer have identified associations in the HLA locus and two loci outside HLA, but the principal genes that control infection and pathogenesis have not been identified. In the present study, we performed GWAS of cervical cancer in East Asian populations, involving 2609 cases and 4712 controls in the discovery stage and 1461 cases and 3295 controls in the follow-up stage. We identified novel-significant associations at 5q14 with the lead single nucleotide polymorphism (SNP) rs59661306 (P = 2.4 × 10-11) and at 7p11 with the lead SNP rs7457728 (P = 1.2 × 10-8). In 5q14, the chromatin region of the GWAS-significant SNPs was found to be in contact with the promoter of the ARRDC3 (arrestin domain-containing 3) gene. In our functional studies, ARRDC3 knockdown in HeLa cells caused significant reductions in both cell growth and susceptibility to HPV16 pseudovirion infection, suggesting that ARRDC3 is involved in the infectious entry of HPV into the cell. Our study advances the understanding of host genes that are responsible for cervical cancer susceptibility and guides future research on HPV infection and cancer development. |
| Databáze: | OpenAIRE |
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