Browsing by Author "Skaar, David"
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Item Open Access Association between PEG3 DNA methylation and high-grade cervical intraepithelial neoplasia.(Infectious agents and cancer, 2021-06) Bosire, Claire; Vidal, Adriana C; Smith, Jennifer S; Jima, Dereje; Huang, Zhiqing; Skaar, David; Valea, Fidel; Bentley, Rex; Gradison, Margaret; Yarnall, Kimberly SH; Ford, Anne; Overcash, Francine; Murphy, Susan K; Hoyo, CathrineBackground
Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.Methods
Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.Results
Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36).Conclusions
While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.Item Open Access Associations between birth and one year anthropometric measurements and IGF2 and IGF2R genetic variants in African American and Caucasian American infants.(Journal of pediatric genetics, 2013-01) Vidal, Adriana C; Overcash, Francine; Murphy, Susan K; Murtha, Amy P; Schildkraut, Joellen M; Forman, Michele R; Demark-Wahnefried, Wendy; Kurtzberg, Joanne; Skaar, David; Jirtle, Randy L; Hoyo, CathrineInsulin-like growth factor 2 receptor (IGF2R) and insulin-like growth factor 2 (IGF2) genetic variants have been inconsistently associated with low birth weight and birth length in Caucasian and Asian infants, however few studies have included African Americans (AA). Generalized linear models and logistic regression models were used to examine associations between IGF2R single nucleotide polymorphisms (SNP) rs629849 and rs8191754, and IGF2 SNP rs680 and infant anthropometric measurements, in a racially diverse birth cohort in Durham County, North Carolina. Caucasian American (CA) carriers of the IGF2R SNP rs629849 were heavier (P = 0.02) and longer (P = 0.003) at birth, however body size at age 1 yr was similar to that of AA. Birth length significantly differed between carriers and non-carriers of the IGF2 rs680 variant in both AA (P = 0.04) and CA infants (P = 0.03). Both AA and CA carriers were 1 cm shorter at birth compared to non-carriers. We found no evidence for an association between rs8191754 and infant anthropometric measurements. Associations between SNPs andone year weight gain were only observed for rs680; CA infant carriers of rs680 variants weighed less than non-carriers at year one (P = 0.03); however, no associations were found in AA infants at year one. Larger studies using ancestral markers are required to disentangle these associations.Item Open Access IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes.(Infect Agent Cancer, 2015) Vidal, Adriana C; Skaar, David; Maguire, Rachel; Dodor, Seyram; Musselwhite, Laura W; Bartlett, John A; Oneko, Olola; Obure, Joseph; Mlay, Pendo; Murphy, Susan K; Hoyo, CathrineBACKGROUND: Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women. METHODS: HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes. RESULTS: After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18. CONCLUSIONS: While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings.