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CD83 gene polymorphisms increase susceptibility to human invasive cervical cancer
Zhengyan Zhang1, Ingrid Borecki, Loan Nguyen
1Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8064, St. Louis, MO 63110, USA. raderj@wustl.edu
Cancer Research
|December 7, 2007
Summary
Researchers identified CD83 as a novel cervical cancer susceptibility gene. This gene shows significant association with invasive cervical cancers, particularly those infected by high-risk human papillomavirus, and is frequently lost in tumors.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- A specific region (6p23) on chromosome 6 was previously identified as a frequent site of loss of heterozygosity (LOH) in cervical cancers.
- Understanding the genetic factors contributing to cervical cancer development is crucial for improving prevention and treatment strategies.
Purpose of the Study:
- To identify novel genes associated with cervical cancer susceptibility.
- To investigate the role of the CD83 gene in the development of cervical cancer.
Main Methods:
- A family-based association study involving 377 family trios was conducted.
- Transcript expression analysis compared normal and cancerous cervical tissues.
- Genomic sequencing was performed on candidate genes, including CD83.
- Single nucleotide polymorphisms (SNPs) near the CD83 gene were analyzed for association with cervical cancer.
- Alternative CD83 transcripts and their frequencies in normal versus cancerous tissue were examined.
- Loss of heterozygosity (LOH) analysis was performed on cervical cancer specimens.
Main Results:
- The CD83 gene was identified as a novel cervical cancer susceptibility gene.
- Five single nucleotide polymorphisms (SNPs) within 8 kb of the CD83 3'-end showed significant allelic association with cervical cancer.
- This association was stronger in women with invasive cancers infected by high-risk human papillomavirus types 16 and 18.
- A specific CD83 transcript variant (variant 3) was more frequent in cervical cancer than in normal cervical epithelium.
- Loss of heterozygosity (LOH) was confirmed in over 90% of cervical cancer specimens.
- CD83 protein was localized to the Golgi apparatus and cell membrane in cervical cancer cell lines.
Conclusions:
- CD83 is a novel susceptibility gene for cervical cancer.
- The association of CD83 with specific human papillomavirus infections suggests a role in HPV-driven cervical carcinogenesis.
- Further research is needed to elucidate the precise role of CD83 in epithelial cells and its contribution to cervical cancer progression.
