Abstract 1351: A CD83 SNP is associated with abnormal Pap test results in high-risk Ohio Appalachian women.

Abstract

Abstract Background: Invasive cervical cancer (ICC) is a leading cause of death in women worldwide. While the prevalence is decreasing in developing countries, it continues to disproportionately affect certain sub-populations in the US. For example, the rate of ICC incidence and mortality in Appalachian women is the highest in the US among white women. Further, Ohio Appalachian women also demonstrate 2-3 times higher rates of abnormal Pap smears compared to the general US population. While many risk factors are known to influence ICC development, little is known about the role of heredity and genetic susceptibility factors. The CD83 gene encodes a transmembrane glycoprotein known to play an important role in immune function. Previous studies suggest that a single nucleotide polymorphism (SNP) in CD83 is associated with increased susceptibility to cervical cancer development. The association was further increased in cervical cancer patients infected any high-risk HPV subtype. Objective: To determine if the CD83 SNP rs750749 is associated with abnormal Pap results and HPV infection in a population-based case control study of Ohio Appalachian women. Methods: The rs750749 SNP was genotyped from blood DNA derived from 288 abnormal Pap cases and 535 normal Pap controls. Odds ratio estimates and 95% confidence intervals were determined using logistic regression. Results: Carriers of the major TT genotype exhibited a 42% increase in the odds of presenting with an abnormal Pap test result compared to carriers of the minor CT and CC genotypes (OR=1.42; 95% CI: 1.05-1.92; p=0.02). Stratifying by HPV status, HPV positive TT carriers exhibited a marginally significant increase of 56% [OR=1.56; 95% CI: 0.95-2.55; p=0.08]. After controlling for smoking, the odds of abnormal Pap results are increased by 35% for TT carriers [OR=1.35; 95% CI: 0.99-1.84; p=0.06]. Conclusions: These findings suggest an association between the CD83 SNP rs750749 and cervical premalignancy in high-risk Ohio Appalachian women. Further studies are needed to determine if the association is maintained in Appalachian ICC patients as well as the biological significance of CD83 in ICC development. Funding Sources: This study was supported by a grant from the National Cancer Institute (P50 CA015632), the Behavioral Measurement Shared Resource at The Ohio State University Comprehensive Cancer Center (National Cancer Institute Grant P30 CA016058) and the Clinical and Translational Science Award (NIH/NCRR Grant Number UL1-RR025755). Citation Format: Joe T. Perrault, Blessing E. Ogbemudia, Marta L. Sears, Cecillia R. DeGraffinreid, Danqi Zhu, Bo Lu, David E. Cohn, Thomas J. Knobloch, Mack T. Ruffin, Electra D. Paskett, Christopher M. Weghorst. A CD83 SNP is associated with abnormal Pap test results in high-risk Ohio Appalachian women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1351. doi:10.1158/1538-7445.AM2013-1351