Skin Cancer Risk Is Increased by Somatic Mutations Detected Noninvasively in Healthy-Appearing Sun-Exposed Skin.

Skin cancer risk is increased by exposure to ultraviolet radiation (UVR). Because UVR exposure accumulates over time and lighter skin is more susceptible to UVR, age and skin tone are risk factors for skin cancer. However, measurements of somatic mutations in healthy-appearing skin have not been used to calculate skin cancer risk. In this study, we developed a noninvasive test that quantifies somatic mutations in healthy-appearing sun-exposed skin and applied it to a 1038-subject cohort. Somatic mutations were combined with other known skin cancer risk factors to train a model to calculate risk. The final model (DNA-Skin Cancer Assessment of Risk) was trained to predict personal history of skin cancer from age, family history, skin tone, and mutation count. The addition of mutation count significantly improved model performance (OR = 1.3, 95% confidence interval = 1.14-1.48; P = 5.3 × 10-6) and made a more significant contribution than skin tone. Calculations of skin cancer risk matched the known United States population prevalence, indicating that DNA-Skin Cancer Assessment of Risk was well-calibrated. In conclusion, somatic mutations in healthy-appearing sun-exposed skin increase skin cancer risk, and mutations capture risk information that is not accounted for by other risk factors. Clinical utility is supported by the noninvasive nature of skin sample collection through adhesive patches.

Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

Patterns of chlamydia/gonorrhea positivity among voluntarily screened New York City public high school students.

PURPOSE: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) are common sexually transmitted infections that disproportionately affect adolescents. Annual screening for CT for sexually active female adolescents is recommended. In 2006, New York City began conducting CT/GC education, screening, and treatment in public high schools. We examine 3-year programmatic outcomes and the relationship between sexual activity, screening, and CT/GC positivity. METHODS: We describe the epidemiology of students who screened and those infected with CT/GC. Univariate, bivariate, and multivariate logistic regression analyses were performed to assess relationships between sex, race/ethnicity, age, sexual activity, and screening status; and the relationship between sexually transmitted infection positivity and sexual activity. RESULTS: Between July 2006 and June 2009, we educated 57,418 students and screened 27,353 (47.6%) for CT/GC; 1,736 (6.3%) students were reported to be infected with either organism. Students who screened positive were more likely to be females (8.9%), report black race (8.3%) and be ≥16 years of age (6.6%-9.7%). Screening rates were 70.6% for students who were sexually active, 27.9% for those who had never had sex, and 47.3% for those who did not respond to the sexual activity question; CT/GC positivity was 7.2%, 1.4%, and 6.1%, respectively. CONCLUSIONS: Black, older adolescent females were most likely to screen positive for CT/GC in this population. A large proportion of students who did not answer the sexual activity question chose to screen for CT/GC and screened positive. School screening programs should offer screening to all students regardless of reported sexual activity. Programs should target females and older adolescents.