Abstract 4835: Genetic variation in EVER1/EVER2 and beta human papillomavirus infection in cutaneous squamous cell carcinoma.
Authors: Rollison Dana E. , Iannacone Michelle R. , Messina Jane L. , Fenske Neil A. , Cherpelis Basil S. , Sondak Vernon K. , Roetzheim Richard G. , Gheit Tarik , Tommasino Massimo , Schmitt Markus , Pawlita Michael 
Published: August 2014

Objective: Cutaneous human papillomavirus (HPV) antibodies and/or DNA in eyebrow hairs have been associated with cutaneous squamous cell carcinoma (SCC) in several case-control studies, including one from New Hampshire and ours from Florida. In the New Hampshire study, a single nucleotide polyomorphism (SNP) in the EVER2 gene (rs72080422) was associated with both SCC and cutaneous HPV seropositivity among controls (Patel et al Int J Cancer, 2008). Additional genetic variants in the EVER1/2 region of chromosome 17q25 have since been identified and shown to be associated with cervical cancer susceptibility (Castro et al Int J Cancer, 2011). We investigated the identical EVER1/2 variants in association with multiple markers of cutaneous HPV infection, including HPV seropositivity, and HPV DNA in eyebrow hairs and SCC tumor tissues. Methods: Patients with histologically-confirmed cutaneous SCC (n=142) were recruited from a university dermatology clinic in Tampa, FL. Controls were patients undergoing skin cancer screening exams who screened negative for skin cancer and reported no history of any type of cancer (n=265). Levels of antibodies against capsid antigens for 15 cutaneous HPV types in genus beta were determined by fluorescent bead-based multiplex serology. DNA for 25 beta-HPV types was measured in eyebrow hairs from cases and controls, and in fresh-frozen tumor tissues from 119 SCC cases using multiplex PCR. Twenty-one SNPs in in the EVER1/2 region of chromosome 17q25 were measured from eyebrow hair DNA, including rs7208422. Associations between EVER1/2 SNPs and SCC, and between EVER1/2 SNPs and HPV serostatus or DNA status, were estimated by odds ratios (OR) and 95% confidence intervals (CI) calculated using logistic regression with adjustment for age and sex. Results: None of the 21 SNPs in the EVER1/2 region were associated with SCC, including rs7208422 in EVER2, for which the TT genotype was observed in 23% of cases and 22% of controls (vs. AA: OR=0.99, 95% CI=0.52-1.90). Seropositivity for any beta-HPV type was not associated with any of the EVER1/2 SNPs among the cases or the controls, nor with seropositivity for HPV types 5 and/or 8 specifically. Beta-HPV DNA in eyebrow hairs was associated with two SNPs among the controls only (rs2290907, AG vs. AA: OR= 2.96, 95% CI=1.37-6.40; rs16970829, AG vs. AA: OR=12.8, 95% CI=1.71-95.90). Among the cases, beta-HPV DNA in tumor tissue was associated with rs7217374 (AG vs AG: OR=3.65, 95% CI=1.42-9.36; AA vs GG: OR=2.02, 95% CI=0.71-5.79), but not with any of the other 20 SNPs. Conclusion: In this small case-control study, genetic variation in the EVER1/2 region was not associated with SCC, and none of the 21 SNPs measured were consistently associated with different biomarkers of beta-HPV infection among cases or controls.

Citation Format: Dana E. Rollison, Michelle R. Iannacone, Jane L. Messina, Neil A. Fenske, Basil S. Cherpelis, Vernon K. Sondak, Richard G. Roetzheim, Tarik Gheit, Massimo Tommasino, Markus Schmitt, Michael Pawlita. Genetic variation in EVER1/EVER2 and beta human papillomavirus infection in cutaneous squamous cell carcinoma. [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 4835. doi:10.1158/1538-7445.AM2013-4835