Interval colorectal cancer (CRC) occasionally is detected in patients who have recently undergone colonoscopy. Systematic evaluation of CRC detected after colonoscopy could identify ways to improve ...the quality and the outcome of colonoscopy.
This study examined cancer diagnoses in the course of the dietary Polyp Prevention Trial, a randomized study of a dietary intervention on recurrence of adenomatous polyps. An algorithm was developed to classify each cancer into one of 4 etiologies: (1) incomplete removal (cancer at the site of previous adenoma), (2) failed biopsy detection (cancer in an area of suspected neoplasia with negative biopsy specimens), (3) missed cancer (large, advanced stage cancer found at a short interval after colonoscopy), or (4) new cancer (small, early stage cancer after a longer time interval).
Of 2079 patients, 13 had cancer detected over 5810 person years of observation (PYO) (2.2 cases/1000 PYO); 7/13 or 53.8% of patients had either a potentially “avoidable” cancer or one detectable at an earlier time interval because of incomplete removal (4/13) or missed cancer (3/13).
Interval cancer occurs despite colonoscopy. Improved quality of colonoscopy may have reduced cancer prevalence or resulted in earlier cancer detection in over 50% of prevalent cancers in the dietary Polyp Prevention Trial.
Studies demonstrating an association between chronic obstructive pulmonary disease and low bone mineral density (BMD) implicate factors distinct from treatments and severity of lung disease in the ...pathogenesis of osteoporosis. Whereas emphysema has been independently associated with vascular disease and other comorbidities, its association with BMD has not been well studied.
We explored the associations of BMD with computed tomography (CT) measures of emphysema and other risk factors in current and former smokers.
One hundred ninety subjects completed a CT scan, pulmonary function testing, questionnaires, and dual x-ray absorptiometry measurements of hip and lumbar spine BMD. Subjects were classified as having normal BMD, osteopenia, or osteoporosis. Demographic, physiologic, and radiographic characteristics were compared and the association of BMD with radiographic emphysema, airflow obstruction, and osteoporosis risk factors was assessed.
No difference existed in age, tobacco exposure, oral steroid use, or physical activity across BMD categories. Both osteopenia and osteoporosis were associated with the presence of airflow obstruction, inhaled corticosteroid use, and female sex, and demonstrated a significant relationship with the presence of visual emphysema (P = 0.0003). Quantitative emphysema, but not CT-measured indices of airway wall thickness, was inversely associated with BMD. Visual emphysema alone was a significant predictor of osteopenia/osteoporosis (odds ratio = 2.55; 95% confidence interval, 1.24-5.25) in a model including obstruction severity, age, sex, and inhaled and oral steroid use.
Radiographic emphysema is a strong, independent predictor of low BMD in current and former smokers. This relationship suggests a common mechanistic link between emphysema and osteopenia/osteoporosis.
Objective We investigated risk factors for Type II (n = 176) vs. Type I (n = 1,576) endometrial cancer (EC) in cases treated at Magee-Womens Hospital between 1996 and 2008. Methods Clinical data were ...available from the University of Pittsburgh Medical Center (UPMC) Network Cancer Registry. Logistic regression was used to estimate the adjusted odds of having Type II EC vs. Type I EC. Risk factors of interest in this analysis were age, race, body mass index (BMI), year of diagnosis, parity, menopausal status, and history of additional primary tumors. Results Relative to women with Type I EC, women with Type II EC were more likely to be older at diagnosis (OR: 1.03 per 1 year increase in age, 95% CI 1.01-1.05), of non-white race (OR: 2.95, 95% CI 1.66-5.27), have a history of additional primary tumors (OR: 1.56, 95% CI 1.05-2.32), and less likely to be obese (OR: 0.45, 95% CI 0.29-0.70). Conclusion In this large retrospective cohort of patients with EC, the striking difference in risk factors associated with Type II vs. Type I tumors suggests that these subtypes represent different disease entities that require different treatment modalities. Currently, Type II cases have a significantly worse prognosis compared to Type I. Further characterization of risk factors associated with developing Type II tumors is needed to prevent this aggressive malignancy.
To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.
We studied lung cancer related to radiographic emphysema and spirometric airflow ...obstruction in tobacco-exposed persons who were screened for lung cancer using chest computed tomography (CT).
Subjects completed questionnaires, spirometry, and low-dose helical chest CT. CT scans were scored for emphysema based on National Emphysema Treatment Trial criteria. Multiple logistic regressions estimated the independent associations between various factors, including radiographic emphysema and airflow obstruction, and subsequent lung cancer diagnosis.
Among 3,638 subjects, 57.5, 18.8, 14.6, and 9.1% had no, trace, mild, and moderate-severe emphysema, and 57.3, 13.6, 22.8, and 6.4% had no, mild (Global Initiative for Chronic Obstructive Lung Disease GOLD I), moderate (GOLD II), and severe (GOLD III-IV) airflow obstruction. Of 3,638 subjects, 99 (2.7%) received a lung cancer diagnosis. Adjusting for sex, age, years of cigarette smoking, and number of cigarettes smoked daily, logistic regression showed the expected lung cancer association with the presence of airflow obstruction (GOLD I-IV, odds ratio OR, 2.09; 95% confidence interval CI, 1.33-3.27). A second logistic regression showed lung cancer related to emphysema (OR, 3.56; 95% CI, 2.21-5.73). After additional adjustments for GOLD class, emphysema remained a strong and statistically significant factor related to lung cancer (OR, 3.14; 95% CI, 1.91-5.15).
Emphysema on CT scan and airflow obstruction on spirometry are related to lung cancer in a high-risk population. Emphysema is independently related to lung cancer. Both radiographic emphysema and airflow obstruction should be considered when assessing lung cancer risk.
Pesticide exposure and liver cancer VoPham, Trang; Bertrand, Kimberly A.; Hart, Jaime E. ...
Cancer Causes & Control,
03/2017, Letnik:
28, Številka:
3
Journal Article, Book Review
Recenzirano
Odprti dostop
Purpose
To review the epidemiologic literature examining pesticide exposure and liver cancer incidence.
Methods
A search of the MEDLINE and Embase databases was conducted in October 2015. Eligibility ...criteria included examining hepatocellular carcinoma (HCC) or primary liver cancer, pesticides as an exposure of interest, and individual-level incidence. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
Forty-eight papers were assessed for eligibility and 15 studies were included in the review. The majority of studies were conducted in China and Egypt (
n
= 8), used a case–control design (
n
= 14), and examined HCC (
n
= 14). Most studies showed no association between self-reported and/or occupational exposure to pesticides and liver cancer risk. Six studies demonstrated statistically significant positive associations, including three biomarker-based studies (two using pre-diagnostic sera) that reported higher serum levels of dichlorodiphenyltrichloroethane (DDT) were associated with increased HCC risk. Studies indirectly measuring pesticide exposure using self-reported exposure, occupation, job-exposure matrices, or geographic residence demonstrated inconsistent results. These studies were limited by exposure assessment methods, lack of confounder information, minimal case confirmation, selection bias, and/or over-adjustment.
Conclusions
There is mixed evidence suggesting a possible association between specific pesticides and HCC risk, with the strongest evidence observed in biomarker-based studies. In particular, organochlorine pesticides, including DDT, may increase HCC risk. Future research should focus on improved pesticide exposure assessment methods, potentially incorporating multiple approaches including biomonitoring while considering the chemicals of interest, historical exposure to address latency periods, and examining specific chemicals and exposure pathways.
Lung cancer and chronic obstructive pulmonary disease (COPD) share environmental risk factors. COPD also increases the risk of lung cancer; however, the molecular mechanisms are unclear.
An ...epigenome-wide association study of lung tumors and cancer-free lung tissue (CFLT) pairs from non–small-cell lung cancer cases with (n = 18) or without (n = 17) COPD was conducted using the HumanMethylation450 beadchip (HM450K). COPD-associated methylation of top-ranked genes was confirmed in a larger sample set, independently validated, and their potential as sputum-based biomarkers was investigated.
Methylation of CCDC37 and MAP1B was more prevalent in lung tumors from COPD than non-COPD cases 54 of 71 (76%) versus 20 of 46 (43%), p = 0.0013 and 48 of 71 (68%) versus 17 of 46 (37%), p = 0.0035, respectively, after adjustment for age, sex, smoking status, and tumor histology. HM450K probes across CCDC37 and MAP1B promoters showed higher methylation in tumors than CFLT with the highest methylation seen in tumors from COPD cases (p < 0.05). These results were independently validated using The Cancer Genome Atlas data. CCDC37 methylation was more prevalent in sputum from COPD than non-COPD smokers (p < 0.005) from two cohorts. CCDC37 and MAP1B expression was dramatically repressed in tumors and CFLT from COPD than non-COPD cases, p less than 0.02.
The reduced expression of CCDC37 and MAP1B associated with COPD likely predisposes these genes to methylation that in turn, may contribute to lung cancer.
Targeted glycoproteomics represents an attractive approach for conducting peripheral blood based cancer biomarker discovery due to the well-known altered pattern of protein glycosylation in cancer ...and the reduced complexity of the resultant glycoproteome. Here we report its application to a set of pooled nonsmall cell lung cancer (NSCLC) case sera (9 adenocarcinoma and 6 squamous cell carcinoma pools from 54 patients) and matched controls pools, including 8 clinical control pools with computed tomography detected nodules but being nonmalignant as determined by biopsy from 54 patients, and 8 matched healthy control pools from 106 cancer-free subjects. The goal of the study is to discover biomarkers that may enable improved early detection and diagnosis of lung cancer. Immunoaffinity subtraction was used to first deplete the topmost abundant serum proteins; the remaining serum proteins were then subjected to hydrazide chemistry based glycoprotein capture and enrichment. Hydrazide resin in situ trypsin digestion was used to release nonglycosylated peptides. Formerly N-linked glycosylated peptides were released by peptide-N-glycosidase F (PNGase F) treatment and were subsequently analyzed by liquid chromatography (LC)−tandem mass spectrometry (MS/MS). A MATLAB based in-house tool was developed to facilitate retention time alignment across different LC−MS/MS runs, determination of precursor ion m/z values and elution profiles, and the integration of mass chromatograms based on determined parameters for identified peptides. A total of 38 glycopeptides from 22 different proteins were significantly differentially abundant across the case/control pools (P < 0.01, Student’s t test) and their abundances led to a near complete separation of case and control pools based on hierarchical clustering. The differential abundances of three of these candidate proteins were verified by commercially available ELISAs applied in the pools. Strong positive correlations between glycopeptide mass chromatograms and ELISA-measured protein abundance was observed for all of the selected glycoproteins.
Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as ...HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo4,5quinoxaline and 2-amino-1-methyl-6-phenylimidazo4,5pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.
Background It is generally accepted that patients with breast cancer métastases have very poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied ...clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease. Populations and methods A total of 557 patients with breast cancer metastasis diagnosis seen at one large urban practice have been followed up between 1 January, 1999 and 30 June, 2010. Demographic, tumor characteristics, clinical factors as predictors of survival were analyzed using log-rank test and Cox regression model. Results The median survival length was 39 months (range 1-138 months) with 154 (27.7%) alive and 403 (72.3%) dead at the end of follow-up period. This study demonstrated that a history of hypertension, ER/PR status, HER2 status, metastasis-free interval, metastatic location (including brain, bone and liver), and BMI at diagnosis with metastatic breast cancer were the most relevant prognostic factors for survival after metastatic disease diagnosis. Conclusion Findings of this study may form a foundation for the growing corpus of knowledge explaining the outcome differences in treatment of patients with metastatic breast cancer, potentially helping to create tailored counseling and personalized treatment approaches for this vulnerable group.
Abstract Non–small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the ...prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERβ and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER)2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERβ and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERβ-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERβ-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERβ-positive cases and squamous cell carcinoma.
PDF
