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Sci Rep. 2019 Sep 11;9(1):13132. doi: 10.1038/s41598-019-49523-0.

The association of integration patterns of human papilloma virus and single nucleotide polymorphisms on immune- or DNA repair-related genes in cervical cancer patients.

Author information

1
Biometrics Research Branch, National Cancer Center, Goyang, Korea.
2
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
3
Genome Medical Science Project (Toyama), National Center for Global Health and Medicine (NCGM), Tokyo, Japan.
4
Department of Microbiology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan.
5
Particle Therapy Research Branch, National Cancer Center, Goyang, Korea.
6
College of Veterinary Medicine, Konkuk University, Seoul, Korea.
7
Center for Breast Cancer, National Cancer Center, Goyang, Korea.
8
Department of Radiobiology and Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan.
9
Translational Research Branch, National Cancer Center, Goyang, Korea.
10
Particle Therapy Research Branch, National Cancer Center, Goyang, Korea. jooyoungcasa@ncc.re.kr.

Abstract

The present study investigated the association between single nucleotide polymorphisms (SNPs) in immune- or DNA repair-related genes and the integration pattern of human papillomavirus (HPV), a promising prognostic marker in cervical cancer. The HPV integration patterns of cervical cancer patients were determined by polymerase chain reaction and in situ hybridization, and categorized as episomal (group A), single-copy or multi-copy tandem repetition integrated (group B), and undetectable HPV types (group C). After sample and SNP quality control, 166,505 SNPs in 161 samples (38, 111, and 12 patients in groups A, B, and C, respectively) were examined. None of the SNPs reached genome-wide significance, and several candidate SNPs for future study were selected, including rs10999435 on chromosome 10q22, rs1322054 on chromosome 9q32-33, and rs10902171 on chromosome 11p15. Luciferase assay identified rs1322054 as the primary functional variant to regulate gene expression in immune cell. Further studies are needed to determine the genetic background of different integration patterns of HPV in cervical cancer patients.

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