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Evaluation of the Association with Cervical Cancer of Polymorphisms in Syndecan-1, a Heparan Sulfate Proteoglycan Involved with Viral Cell Entry

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; ² Johns Hopkins University School of Medicine, Baltimore, Maryland; ³ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center; ⁴ Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington; and ⁵ Laboratory of Genomic Diversity, Science Applications International Corporation-Frederick, Inc., NCI-Frederick, Frederick, Maryland

Requests for reprints: Kelly J. Yu, Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, 6120 Executive Boulevard, Suite 550, Bethesda, MD 20852. Phone: 301-496-1691; Fax: 301-402-0916. E-mail: yuke{at}mail.nih.gov

Infection with 1 of 15 oncogenic human papillomaviruses is known to be linked to the development of all histologic forms of cervical cancer. We evaluated whether polymorphisms in syndecan-1 (SDC-1), a gene whose protein product is believed to be involved in human papillomavirus entry into epithelial cells, were associated with histologic subtypes of cervical cancer. A total of 293 in situ/invasive adenocarcinoma cases, 260 in situ/invasive squamous cell carcinoma cases, and 478 controls from two studies conducted in the Eastern United States and Seattle area were evaluated. DNA from peripheral blood was used for testing. We sequenced 5 exons and 60 nucleotides upstream of the start codon for SDC-1 in a random subset of 50 cases and 50 controls from the Eastern U.S. Study and identified two polymorphisms (E84E, rs2230924 and Pro-27 C T, rs11544860). PCR-based testing was done to evaluate risk associated with these two polymorphisms. Polymorphisms of SDC-1 were not associated with risk of squamous cell carcinomas of the cervix. Similarly, there was no evidence for an association between SDC-1 exon 3 polymorphisms and risk of cervical adenocarcinomas. A marginally significant increase in risk of cervical adenocarcinoma was associated with the presence of the Pro-27 polymorphism (pooled odds ratios, 1.6; 95% confidence intervals, 0.99-2.6), an effect that was restricted to the Eastern U.S. Study. Our results indicate a lack of association between SDC-1 polymorphisms and risk of squamous cell carcinomas of the cervix. An association between SDC-1 Pro-27 polymorphism and cervical adenocarcinoma cannot be ruled out. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2504–8)