Ambient air pollution and lung cancer risk among never-smokers in the Women's Health Initiative.

BACKGROUND: Ambient air pollution is classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, epidemiologic studies supporting this classification have focused on lung cancer mortality rather than incidence, and spatial and temporal resolutions of exposure estimates have varied considerably across studies. METHODS: We evaluated the association of outdoor air pollution and lung cancer incidence among never-smoking participants of the Women's Health Initiative (WHI) study, a large, US-based cohort of postmenopausal women (N = 65,419; 265 cases). We used geospatial models to estimate exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) based on residential addresses at baseline and throughout follow-up. We also characterized exposures to traffic-related air pollution by proximity to major roadways. We estimated hazard ratios (HRs) for the risk of lung cancer in association with these exposure metrics using Cox proportional hazards regression models. RESULTS: No compelling associations of PM2.5 and NO2 exposures with lung cancer risk were observed. An increased risk of lung cancer was observed when comparing those individuals with residences <50 versus ≥200 meters from a primary limited access highway (HR = 5.23; 95% confidence interval = 1.94, 14.13). CONCLUSIONS: Our results do not exclude lung cancer risk estimates observed in association with PM2.5 and NO2 exposures identified in previous studies. Our results suggest that residential proximity to major roadways may be a proxy for carcinogenic exposures not correlated with PM2.5 or NO2 levels. New studies of air pollution and lung cancer incidence should characterize additional aspects of proximity to major roadways.

Low bone mineral density linked to colorectal adenomas: a cross-sectional study of a racially diverse population.

BACKGROUND: Epidemiologic studies suggest that lower bone mineral density (BMD) is associated with an increased risk for colorectal adenoma/cancer, especially in postmenopausal women. The aim of this study is to investigate the association between osteopenia and/or osteoporosis and colorectal adenomas in patients from a New York community hospital. METHODS: We performed a cross-sectional observational study on 200 patients who underwent screening colonoscopies and bone density scan (dual-energy X-ray absorptiometry) at Nassau University Medical Center from November 2009 to March 2011. Among these, 83 patients were identified as osteoporosis (T score of -2.5 or below) and 67 were osteopenia (T score between -1.0 and -2.5). Logistic regression model was performed to assess the association between osteopenia and/or osteoporosis and colorectal adenomas. RESULTS: Among the patients with osteopenia and osteoporosis, the mean ages were 59.1 years [standard deviation (SD) =8.9] and 61.5 (SD =8.9), respectively. There were 94.0%, 85.1% and 74.7% women, respectively, in normal BMD, osteopenia and osteoporosis groups. The prevalence of colorectal adenomas was 17.9% and 25.3% in the osteopenia and osteoporosis groups, respectively, and 18.0% in the normal BMD group. After adjustment for potential confounders including age, sex, race, body mass index (BMI), tobacco use, alcohol use, history of diabetes, hypertension, or dyslipidemia, osteoporosis was found to be associated with presence of colorectal adenomas more than 2, compared to the normal BMD group. No significant associations were found for the prevalence, size, and location of adenomas. CONCLUSIONS: Our study suggests that osteoporosis is significantly associated with the presence of multiple colorectal adenomas. Prospective studies with a larger sample size are warranted in the future.

Misnomers in dermatology: an update.

The name of a condition in dermatology, gives a clue regarding the clinical feature, etiology, or histopathology of the disease. A disease might have been termed wrongly due to its resemblance to another known condition. Misnomers often mislead a physician regarding the etiology or histopathology of the condition. Here is a list of misnomers, with explanation, and the appropriate name in parentheses.

Level VI lymph node dissection does not decrease radioiodine uptake in patients undergoing radioiodine ablation for differentiated thyroid cancer.

BACKGROUND: In patients with well-differentiated thyroid cancer, the incidence of pathologic central compartment lymph node metastases is reported to be approximately 50%. Recently level VI lymph node dissection has been advocated as a means of reducing recurrence rates in these patients, even if there are no clinically apparent nodal metastases. This study investigates whether level VI lymph node dissection decreases the percent radioiodine uptake when patients undergo radioiodine ablation. METHODS: All thyroid cancer patients entered into the endocrine surgery database at a tertiary care center from 2006 to 2010 were reviewed. Those treated with radioactive iodine were analyzed with respect to performance of a central compartment lymph node dissection and the percent uptake of radioiodine ((131)I) on the preablation scan at 72 h. RESULTS: There were 277 patients with well-differentiated thyroid cancer who underwent radioiodine ablation. In all, 75% were female, and the mean age was 47.7 years. A total of 87 patients underwent total thyroidectomy and level VI lymph node dissection (TT + LVIND). The mean number of level VI nodes resected was 6 (1-27), and 60.9% of patients had nodal metastases. Altogether, 190 had a total thyroidectomy (TT) only, and the median number of nodes resected was 0 (0-10). The percent uptake of radioiodine on the preablation scan was 0.93% in patients who had undergone TT + LVIND and 1.2% in those with TT alone (p = 0.17). The median number of radioactive foci noted within the thyroid bed was two in both groups (p = 0.64). The mean preablation thyroglobulin levels, measured after thyroxine withdrawal or thyrogen stimulation, were 4.0 ng/ml in the TT + LVIND group versus 4.7 ng/ml in the TT group (p = 0.07). The average ablative dose of (131)I was 111.8 mCi in the dissection group and 98.5 mCi in the TT-only group. CONCLUSIONS: There is no evidence that uptake of (131)I is reduced by performance of a central neck dissection in patients with well-differentiated thyroid cancer. Preablation thyroglobulin levels were not altered by level VI lymph node dissection.

DNA methylation supports intrinsic epigenetic memory in mammalian cells.

We have investigated the role of DNA methylation in the initiation and maintenance of silenced chromatin in somatic mammalian cells. We found that a mutated transgene, in which all the CpG dinucleotides have been eliminated, underwent transcriptional silencing to the same extent as the unmodified transgene. These observations demonstrate that DNA methylation is not required for silencing. The silenced CpG-free transgene exhibited all the features of heterochromatin, including silencing of transcriptional activity, delayed DNA replication, lack of histone H3 and H4 acetylation, lack of H3-K4 methylation, and enrichment in tri-methyl-H3-K9. In contrast, when we tested for transgene reactivation using a Cre recombinase-mediated inversion assay, we observed a marked difference between a CpG-free and an unmodified transgene: the CpG-free transgene resumed transcription and did not exhibit markers of heterochromatin whereas the unmodified transgene remained silenced. These data indicate that methylation of CpG residues conferred epigenetic memory in this system. These results also suggest that replication delay, lack of histone H3 and H4 acetylation, H3-K4 methylation, and enrichment in tri-methyl-H3-K9 are not sufficient to confer epigenetic memory. We propose that DNA methylation within transgenes serves as an intrinsic epigenetic memory to permanently silence transgenes and prevent their reactivation.