Despite the fact that cervical cancer is one of the leading causes of death in women worldwide, research has yet to elucidate why some HPV-infected women develop cancerous lesions while others are able to clear the infection. Previous studies have shown that HPV integration status may be associated with cervical cancer development, and yet, host genetic factors that may be involved in the viral integration process have not yet been identified. The purpose of this study was to examine the association between both HPV 18 viral integration status and single nucleotide polymorphisms (SNPs) in non-homologous end-joining (NHEJ) DNA repair pathway genes on cervical dysplasia. Specifically, we sought to compare women with no dysplasia to those with low-grade or high-grade squamous intraepithelial lesions. METHODS: A total of 765 women were selected from two large trials designed to evaluate optical technologies for cervical cancer. Genotyping was performed using the Illumina Golden Gate platform. HPV 18 integration status was determined using a previously established protocol. Chi-square tests were conducted to determine which SNPs were associated with normal cytology, low-grade, or high-grade lesions. Among participants with cervical dysplasia, polytomous logistic regression models were used to evaluate the effect of each polymorphism on viral integration status. An additive genetic model was used for all tests. P-values were adjusted using the false discovery rate method. RESULTS: Women with high-grade lesions were significantly younger than women with low-grade or no lesions. Tag-SNPs in 13 DNA repair genes, including MRE11A, ATM, and XRCC4, were significantly associated with cervical dysplasia. Most participants had a mix of both episomal and integrated HPV 18. Tag-SNPs in the XRCC4, PRKCH, and MRE11A genes were found to be significantly associated with HPV 18 integration status. CONCLUSION: Our study indicates that host genetic variation in NHEJ DNA repair pathway genes, including MRE11A and XRCC4, are significantly associated with HPV 18 integration, and that these genes may play a key role in determining cervical cancer development and progression. This is the first study to examine host genetic variation in association with the viral integration event.
Predictors of Cancer Survivors' Receptivity to Lifestyle Behavior Change InterventionsBasen-Engquist K, Carmack C, Blalock J, Baum G, Rahming W, Demark-Wahnefried W Purpose: To assess cancer survivors' interest in lifestyle behavior change interventions, and to identify predictors of interest.Methods: Mailed surveys were sent to a stratified random sample of breast, colorectal, and prostate cancer survivors ascertained from the MD Anderson tumor registry and departmental databases. Surveys queried survivors about their diet, exercise, and smoking behaviors; symptoms; and their interest in interventions.Results: Surveys were received from 1053 cancer survivors. Roughly half of the sample were very/extremely interested in programs to help them get in shape (45%), e...
