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The article discusses research on the possible association between colorectal cancer risk and leukocyte methylated cytosine (5-mC) levels. It explains significant role of DNA methylation in cellular process regulation. It reports analysis of leukocyte levels in Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants. The correlation between genomic leukocyte DNA methylation levels and lifestyle characteristics of control subjects is also explored.

CXCL12 is a chemotactic cytokine that has pro-metastatic functions in several malignancies through interactions with its receptor, CXCR4. CXCL12 is an estrogen-regulated gene, and notably, estrogen is a major risk factor for endometrial cancer (EC) development. As few studies examine concurrent CXCL12, CXCR4, and estrogen receptor (ER) expression in EC patients, we examined this pathway in 199 EC patients with data from the University of Pittsburgh Medical Center Cancer Registry. Immunohistochemistry (IHC) was used to detect CXCR4, CXCL12 and ER protein expression. As CXCR4 expression was positive in all cases, this investigation focused on associations between CXCL12 and ER expression, clinicopathologic factors and survival outcomes using chi-square tests, Kaplan-Meier graphs, and log-rank tests. CXCL12 expression was negative in 63 cases (32%) and positive in 136 cases (68%). Negative CXCL12 expression was borderline significantly associated with metastasis (χ2 p = 0.07). ER expression was negative in 75 cases (38%) and positive in 124 cases (62%). Positive ER expression was significantly associated with low grade and early stage tumors (χ2 p < 0.001). CXCL12 and ER were not significantly associated (χ2 p = 0.11). Positive CXCL12 expression was associated with longer overall survival (OS) (log-rank p = 0.006) and longer recurrence-free survival (RFS) (log-rank p = 0.01) in ER negative patients, but not in ER positive patients. We identified a unique molecular signature associated with better OS and RFS in EC patients. In addition to pathological characteristics of the tumor, expression of CXCL12 and ER may be clinically useful for assigning adjuvant treatment to EC cases. [ABSTRACT FROM AUTHOR]

Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (Pinteraction = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11–1.85, Ptrend = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30–0.84, Ptrend = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk. [ABSTRACT FROM AUTHOR]

Background and Objective: Diagnosis of colorectal cancer after negative findings on endoscopic evaluation raises concern about the effectiveness of endoscopic screening. We contrast screening-detected cancers with cancers not detected by screening among participants assigned to flexible sigmoidoscopy (FSG) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to determine the reasons for the lack of detection of prevalent lesions. Design: Cancers detected within 1 year of a screening FSG with abnormal findings were classified as screening detected. All other cancers were categorized, based on cancer stage and years until detection, as either not detectable or prevalent but not detected at the time of screening. Setting/Patients: A total of 77,447 subjects in the multicenter PLCO trial. Main Outcome Measurements: A total of 977 colorectal cancers were diagnosed with a mean follow-up of 11.5 years. Results: A total of 243 (24.9%) cancers were screening detected, 470 (48.1%) were not detectable at screening, and 264 (27.0%) were considered prevalent but not detected. Among prevalent nondetected lesions, 35.6% (n = 94) were attributed to problems in patient compliance (58 never screened, 34 delayed colonoscopy follow-up, and 2 inadequate bowel preparation), 43.9% (n = 116) were attributable to a limitation in the FSG procedure (97 beyond the reach of the sigmoidoscope and 19 inadequate depth of insertion on FSG), and 20.5% (n = 54) were caused by endoscopist limitation (33 missed on FSG, 21 missed at initial colonoscopy) (P < .0001). Had colonoscopy instead of FSG been used for screening, an additional 15.6% and as many as 19.0% of cancers may have been screening-detected. Limitations: These estimates are reasonable approximations, but biological variability precludes precise determinations. Conclusions: Prevalent nondetected cancers were more often attributable to problems with patient compliance or limitations in the FSG procedure than to missed lesions. Colonoscopy instead of FSG could have moderately increased the detection of cancer via screening. [Copyright &y& Elsevier]

Background Among randomized trials evaluating flexible sigmoidoscopy (FSG) for its effect on colorectal cancer mortality, only the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial screened its participants more than one time. We report outcomes from the PLCO screening FSG program and evaluate the increased yield produced by a second FSG. Methods Participants were screened by 60-cm FSG in 10 regional screening centers at study entry and 3 or 5 years later, depending on the time of random assignment. Results from subsequent diagnostic intervention were tracked and recorded in a standardized fashion, and outcomes were compared according to sex and age. The protocol discouraged repeat FSG in persons with colorectal cancer or adenoma diagnosed after the initial FSG. Results Of 77 447 enrollees, 67 073 (86.6%) had at least one FSG and 39 443 (50.9%) had two FSGs. Diagnostic intervention occurred in 74.9% after a positive first FSG and in 78.7% after a positive repeat FSG. The second FSG increased the screening yield by 32%: Colorectal cancer or advanced adenoma was detected in 37.8 per 1000 persons after first screening and in 49.8 per 1000 persons after all screenings. The second FSG increased the yield of cancer or advanced adenoma by 26% in women and by 34% in men. Of 223 subjects who received a diagnosis of colorectal carcinoma within 1 year of a positive FSG, 64.6% had stage I and 17.5% had stage II disease. Conclusions Repeat FSG increased the detection of colorectal cancer or advanced adenoma in women by one-fourth and in men by one-third. Screen-detected carcinomas were early stage (stage I or II) in greater than 80% of screened persons. Colorectal cancer mortality data from the PLCO, as the definitive endpoint, will follow in later publications. [ABSTRACT FROM PUBLISHER]

Background The prostate component of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen (PSA) testing and digital rectal examination (DRE). Mortality after 7–10 years of follow-up has been reported previously. We report extended follow-up to 13 years after the trial. Methods A total of 76 685 men, aged 55–74 years, were enrolled at 10 screening centers between November 1993 and July 2001 and randomly assigned to the intervention (organized screening of annual PSA testing for 6 years and annual DRE for 4 years; 38 340 men) and control (usual care, which sometimes included opportunistic screening; 38 345 men) arms. Screening was completed in October 2006. All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31, 2009, were ascertained. Relative risks (RRs) were estimated as the ratio of observed rates in the intervention and control arms, and 95% confidence intervals (CIs) were calculated assuming a Poisson distribution for the number of events. Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age, comorbidity status, and pretrial PSA testing. All statistical tests were two-sided. Results Approximately 92% of the study participants were followed to 10 years and 57% to 13 years. At 13 years, 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm. Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years, respectively, resulting in a relative increase of 12% in the intervention arm (RR = 1.12, 95% CI = 1.07 to 1.17). After 13 years of follow-up, the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years, respectively, resulting in a non-statistically significant difference between the two arms (RR = 1.09, 95% CI = 0.87 to 1.36). No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age (Pinteraction = .81), pretrial PSA testing (Pinteraction = .52), and comorbidity (Pinteraction = .68). Conclusions After 13 years of follow-up, there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening, which forms part of usual care, and there was no apparent interaction with age, baseline comorbidity, or pretrial PSA testing. [ABSTRACT FROM PUBLISHER]

The article discusses a study of the effect on mortality of screening for lung cancer (LC) using modern chest radiographs (CR). The authors invited 154,901 participants aged 55 through 74 years, who were randomized to intervention group (IG) and to usual care group (UCG). Participants in the IG were assigned to undergo annual postero-anterior view CR for four years. Meanwhile, UCG participants were assigned to received their usual medical screening at 1 of 10 centers across the U.S. The authors found that annual screening with CR did not significantly decrease LC mortality compared with UC.

The article provides information on a study which investigated the survival rate in patients with squamous cell carcinoma of the head and neck (SCCHN) with regard to the genotypes ERCC2 A35931C and CCND1 G870A. Patients are grouped according to stage and radiation treatment. It concludes that germline differences in DNA-repair or cell-cycle control may improve treatment outcome in patients treated with DNA-damaging agents.

This article discusses a study which reviewed the effect of screening for ovarian cancer with cancer antigen 125 (CA-125) on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The study conducted a trial of a group of women who received either annual screening or usual care. It analyzed secondary outcomes such as ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures. It concluded that CA-125 did not reduce ovarian cancer mortality.

Abstract: Classic tissue effects of β 2-adrenergic receptor activation include skeletal muscle glycogenolysis and vascular smooth muscle relaxation, factors relevant to obesity and hypertension, respectively. In a population-based study, we examined 2 common amino acid substitutions in the β 2-adrenergic receptor gene (ADRB2) in relation to body composition and blood pressure. A cross-sectional analysis of 1893 African-descent men living in Tobago and participating in a prostate cancer screening study was performed. Body mass index, waist circumference, blood pressure, dual-energy x-ray absorptiometry body composition, and ADRB2 (Arg16Gly; Gln27Glu) genotype were determined. Twenty-six percent were obese (body mass index ≥30 kg/m2), and 50% were hypertensive. ADRB2 Arg16Gly and Gln27Glu alleles were in linkage disequilibrium (D′ = 0.96, r 2 = 0.15). ADRB2 16Gly-containing and 27Glu-containing genotypes were equally frequent in low, medium, and high tertiles of percentage of body fat mass (16Gly-containing genotypes: 73.4%, 74.4%, and 74.5%, P trend = .66; 27Glu-containing genotypes: 27.6%, 23.8%, and 25.4%, P trend = .39) and in normal blood pressure, prehypertensive, and hypertensive men (16Gly-containing genotypes: 73.4%, 72.8%, and 74.4%, P trend = .61; 27Glu-containing genotypes: 25.6%, 24.1%, and 26.7%, P trend = .50). In a high-obesity and high–hypertension risk population with ancestry in common with African Americans, genetic variation defined by 2 common ADRB2 amino acid substitutions was not associated with body composition or hypertension. [Copyright &y& Elsevier]

Objectives. To understand the contribution of intraoperative and postoperative hospital costs to total hospital costs, examine the costs associated with specific hospital services in the postoperative period, and recognize the impact of patient factors on hospital costs.Study Design. Case series with chart review.Setting. Large tertiary care teaching hospital system.Subjects and Methods. Using the Pittsburgh Head and Neck Organ-Specific Database, 119 patients were identified as having total laryngectomy with bilateral selective neck dissection and primary closure from 1999 to 2009. Cost data were obtained for 112 patients. Costs include fixed and variable costs, adjusted to 2010 US dollars using the Consumer Price Index.Results. Mean total hospital costs were $29 563 (range, $10 915 to $120 345). Operating room costs averaged 24% of total hospital costs, whereas room charges, respiratory therapy, laboratory, pharmacy, and radiology accounted for 38%, 14%, 8%, 7%, and 3%, respectively. Median length of stay was 9 days (range, 6-43), and median Charlson comorbidity index score was 8 (2-16). Patients with ≥1 day in the intensive care unit had significantly higher hospital costs ($46 831 vs $24 601, P < .01). The authors found no significant cost differences with stratification based on previous radiation therapy ($27 598 vs $29 915 with no prior radiation, P = .62) or hospital readmission within 30 days ($29 483 vs $29 609 without readmission, P = .97).Conclusion. This is one of few studies in surgery and the first in otolaryngology to analyze hospital costs for a relatively standardized procedure. Further work will include cost analysis from multiple centers with investigation of global cost drivers. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

The article offers information on a study which examined the advantages of lung cancer screening, particularly, its effect on healthcare use. The study also evaluated variations in use over time and how variations over time differed among the screening outcome groups. A review of the related literature on cancer screening methods such as spiral computed tomography (CT) is offered. The characteristics of the study population is described. A discussion on the study findings is detailed.

Objective: To identify trends in a residual category of cancers not typically associated with tobacco, screening, or human immunodeficiency virus (HIV) infection.Methods: For persons aged 20-84, we used sex- and race-specific age-period-cohort (APC) models to describe temporal patterns of incidence (1975-2004) and mortality (1970-2004) in the U.S. for a residual cancer category that excluded non-Hodgkin lymphoma, Kaposi sarcoma, and cancer of the oral cavity and pharynx, esophagus, pancreas, larynx, lung and bronchus, urinary bladder, kidney and renal pelvis, colon and rectum, prostate, female breast, and cervix uteri.Results: Age-specific incidence rose (0.1-0.9% per year, on average) in every sex-race group, with factors related to both time period and birth cohort membership appearing to accelerate the increases in women. Age-specific mortality fell (0.6-0.9% per year, on average) for black and white men and women, with the declines decelerating in white women but accelerating in the other sex-race groups. Extrapolations of APC models predicted higher age-adjusted incidence rates in white women (11%), black women (5%), and white men (4%) in 2005-2009, relative to 2000-2004, and lower rates in black men (-3%), accompanied by lower age-adjusted mortality rates in every sex-race group (-8% in black men, -3% in black women, -1% in white men, and -1% in white women).Conclusions: The possibility that increased incidence in women over time reflects changes in underlying risks, diagnostic practices, or better case ascertainment should be actively explored. Declining mortality may signify improvements in cancer care. [ABSTRACT FROM AUTHOR]

Prospective studies of lifestyle and non-Hodgkin lymphoma (NHL) are conflicting, and some are inconsistent with case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was used to evaluate risk of NHL and its subtypes in association with anthropometric factors, smoking, and alcohol consumption in a prospective cohort study. Lifestyle was assessed via questionnaire among 142,982 male and female participants aged 55–74 years enrolled in the PLCO Trial during 1993–2001. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards regression. During 1,201,074 person-years of follow-up through 2006, 1,264 histologically confirmed NHL cases were identified. Higher body mass index (BMI; weight (kg)/height (m)2) at ages 20 and 50 years and at baseline was associated with increased NHL risk (Ptrend < 0.01 for all; e.g., for baseline BMI ≥30 vs. 18.5–24.9, hazard ratio = 1.32, 95% confidence interval: 1.13, 1.54). Smoking was not associated with NHL overall but was inversely associated with follicular lymphoma (ever smoking vs. never: hazard ratio = 0.62, 95% confidence interval: 0.45, 0.85). Alcohol consumption was unrelated to NHL (drinks/week: Ptrend = 0.187). These data support previous studies suggesting that BMI is positively associated with NHL, show an inverse association between smoking and follicular lymphoma (perhaps due to residual confounding), and do not support a causal association between alcohol and NHL. [ABSTRACT FROM PUBLISHER]

The article presents a study which assesses cancer trends in the U.S. by evaluating generational risk for three cancer groups including tobacco-related cancer, screen-detectable cancer, and cancer which are unrelated to tobacco or screening. Data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program were analyzed to obtain specific data of incidence and mortality. Results revealed higher risks of cancer unrelated to tobacco or screening in adults compared to their parents.

Background & Aims: The recommended timing of surveillance colonoscopy for individuals with adenomatous polyps is based on adenoma histology, size, and number. The burden and cost of surveillance colonoscopy are significant. The aim of this study was to examine the use of surveillance colonoscopy on a community-wide basis. Methods: We retrospectively queried participants in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial in 9 US communities about use of surveillance colonoscopy. Subjects whose initial colonoscopy showed advanced adenoma (AA), nonadvanced adenoma (NAA), or no adenoma (NA) findings were included. Colonoscopy examinations were confirmed by reviewing colonoscopy reports. Results: Of 3876 subjects selected for inquiry, 3627 (93.6%) responded. The cumulative probability of a surveillance colonoscopy within 5 years was 58.4% (n = 1342) in the AA group, 57.5% in those with ≥3 NAAs (n = 117), 46.7% in those with 1–2 NAAs (n = 905), and 26.5% (n = 1263) in subjects with NAs. Within 7 years, 33.2% of subjects with AAs received ≥2 surveillance examinations versus 26.9% for those with ≥3 NAAs, 18.2% for those with 1 or 2 NAAs, and 10.4% for those with NAs. Incomplete colonoscopy, family history of colorectal cancer, or interval adenomatous findings could explain only a minority of surveillance colonoscopy in low-risk subjects. Conclusions: In community practice, there is substantial overuse of surveillance colonoscopy among low-risk subjects and underuse among subjects with AAs. Interventions to better align use of surveillance colonoscopy with risk for advanced lesions are needed. [Copyright &y& Elsevier]

Long-term exposure to arsenic above 50 μg/L in drinking water has been related to multiple types of cancers. Few epidemiologic studies conducted in the US have detected an association between regional exposures below this level in drinking water and corresponding cancer occurrence rates. This county-level ecologic study evaluates arsenic levels in ground water and its association with targeted cancer incidence in Idaho, where some regions have been found to contain higher arsenic levels. Using cancer incidence data (1991–2005) from the Cancer Data Registry of Idaho and arsenic data (1991–2005) from the Idaho Department of Environmental Quality, we calculated the age-adjusted incidence rate for cancers of the urinary bladder, kidney and renal pelvis, liver and bile duct, lung and bronchus, non-Hodgkin’s lymphoma (NHL), and all malignant cancers according to arsenic levels in ground water. Multivariate regression analysis was applied to evaluate the relationship between arsenic levels in ground water and cancer incidence. For males, but not for females, age-adjusted incidence for lung cancer and all malignant cancers was significantly higher in the intermediate arsenic counties (2–9 μg/L, n = 16) and the high arsenic counties (≥10 μg/L, n = 5) compared to the low arsenic counties (<2.0 μg/L, n = 23). When adjusted for race, gender, population density, smoking and body mass index (BMI), no relationship was found between arsenic levels in ground water and cancer incidence. In this ecological design, exposure to low-level arsenic in ground water is not associated with cancer incidence when adjusting for salient variables. For populations residing in southwestern Idaho, where arsenic has been found to exceed 10 μg/L in ground water, individual risk assessment is required in order to determine whether there is a link between long-term arsenic exposure at these levels and cancer risk. [ABSTRACT FROM AUTHOR]

Objective: The Wnt/APC/beta-catenin signaling pathway, which includes frizzled-related protein (FRZB), plays a critical role in the development of colorectal cancer, and recent evidence suggests that the functional polymorphism, FRZB Arg324Gly, may be associated with risk for this disease. To determine if this finding could be replicated, we investigated the association between two FRZB polymorphisms (Arg324Gly and Arg200Trp) and the risk of colorectal adenoma and cancer in nested case-control studies.Methods: Participants consisted of 1,709 adenoma cases, 620 cancer cases, and 1,849 controls within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations with colorectal neoplasia.Results: No association was observed for either polymorphism or any haplotypes with colorectal adenoma or colorectal cancer (p>0.05 for all).Conclusion: Our study does not support the previously observed association between the FRZB 324Gly variant and colorectal cancer risk. However, further study of additional genetic variants within this pathway is still warranted, given the important role of the Wnt signaling pathway in colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and is important to carcinogenesis. Previous studies relating circulating levels of VEGF to breast cancer have been limited by small numbers of participants and lack of adjustment for confounders. We studied the association between serum VEGF and breast cancer in an unmatched case-control study of 407 pre- and postmenopausal women (n = 203 cases, n = 204 controls). Logistic regression was used to model the breast cancer risk as a function of natural log transformed VEGF levels adjusted for age, Gail score, education, physical activity, history of breastfeeding, serum testosterone, and hormone therapy (HT) use. The majority of the population was postmenopausal (67.6%) and the average age was 56 years; age and menopausal status were similar among cases and controls. Geometric mean VEGF levels were non-significantly higher in cases (321.4 pg/ml) than controls (291.4 pg/ml; p = 0.21). In a multivariable model, the odds of breast cancer was 37% higher for women with VEGF levels > or =314.2 pg/ml compared to those with levels below 314.2 pg/ml, albeit not significantly (p = 0.16). There was no interaction between VEGF and menopausal status (p = 0.52). In this case-control study, VEGF was not significantly associated with breast cancer risk in pre- and postmenopausal women. [ABSTRACT FROM AUTHOR]

The article provides information on a study on the enhanced office and patient management on a compliance with colorectal cancer screening. The study aims to analyze the methods for promoting colorectal cancer screening in primary care practice. The impact of a tailored versus nontailored physician recommendation letter and an enhanced versus nonenhanced physician office and patient management intervention on colorectal cancer screening adherence were evaluated through 2x2 factorial randomnized clinical trial. Results showed that the enhanced office and patient management system significantly improved colorectal cancer screening.

Background & Aims: Surveillance colonoscopy is recommended for subjects with a history of adenomas but there is limited information on the yield of surveillance. Methods: A sample of subjects in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial with abnormal flexible sigmoidoscopy and follow-up colonoscopy were queried about subsequent surveillance colonoscopy over a 10-year period. Medical records were obtained to verify procedure dates and histologic findings. Subjects with advanced adenomas, nonadvanced adenoma, nonadenomatous polyps, and no polyps at baseline were included. Results: At the first surveillance, 10.5% had advanced adenoma and 37% had any adenoma in the advanced adenoma group (n = 1057), compared with rates of 6.8% and 32% (nonadvanced adenoma: n = 765), 4.9% and 22% (nonadenomatous polyps: n = 658), and 3.1% and 16% (no polyps: n = 127) (P < .0001, linear trend test). Mean (SD) time intervals (years) from baseline colonoscopy to first surveillance were 3.4 (2.0) for advanced adenoma, 4.3 (2.0) for nonadvanced adenoma, 4.5 (2.0) for nonadenomatous polyps, and 4.7 (2.0) for no polyps. There were no increasing (or decreasing) trends in the observed rate of advanced adenoma or any adenoma with time to the initial surveillance examination in any baseline group. Among subjects with a second surveillance examination, adenoma findings at both baseline and first surveillance influenced the rates of advanced adenoma and any adenoma at second surveillance. Conclusions: Subjects with baseline advanced adenomas are more likely to have recurrent advanced adenomas at initial surveillance. The lack of association between recurrence rates and time to surveillance suggests limitations in our understanding of the biology of adenoma development. [Copyright &y& Elsevier]

OBJECTIVE To describe the results of the first four rounds (T0-T3) of prostate cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial (designed to determine the value of screening in the four cancers), that for prostate cancer is evaluating whether annual screening with prostate-specific antigen (PSA) and a digital rectal examination (DRE) reduces prostate cancer-specific mortality. SUBJECTS AND METHODS In all, 38 349 men aged 55–74 years were randomized to undergo annual screening with PSA (abnormal >4.0 ng/mL) and a DRE. The follow-up of abnormal screening results was at the discretion of subjects’ physicians. PLCO staff obtained records related to diagnostic follow-up of positive screen results. RESULTS Compliance with screening decreased slightly from 89% at baseline to 85% at T3. Both PSA positivity rates (range 7.7–8.8% at T0-T3) and DRE positivity rates (range 6.8–7.6% at T0-T3) were relatively constant over time. The positive predictive value (PPV) of a PSA level of >4.0 ng/mL decreased from 17.9% at T0 to 10.4–12.3% at T1-T3; the PPV for DRE (in the absence of a positive PSA test) was constant over time (2.9–3.6%). Cancer was diagnosed in 1902 men (4.9%). Screen-detected cancers at T0 (549) were more likely to be clinical stage III/IV (5.8%) and to have a Gleason score of 7–10 (34%) than screen-detected cancers at T1-T3 (1.5–4.2% stage III/IV and 24–27% Gleason score 7–10 among 1054 cases). CONCLUSION The present findings on serial prostate screening are similar to those reported from other multi-round screening studies. Determining the effect of PSA screening on prostate cancer mortality awaits further follow-up. [ABSTRACT FROM AUTHOR]

Rationale: The role of computed tomography (CT) screening for lung cancer is controversial, currently under study, and not yet fully elucidated.Objectives: To report findings from initial and 1-year repeat screening low-radiation-dose CT of the chest and 3-year outcomes for 50- to 79-year-old current and ex-smokers in the Pittsburgh Lung Screening Study (PLuSS).Methods: Notified of findings on screening CT, subjects received diagnostic advice from both study and personal physicians. Tracking subjects for up to three years since initial screening, we obtained medical records to document diagnostic procedures, lung cancer diagnoses, and deaths.Measurements and Main Results: 3,642 and 3,423 subjects had initial and repeat screening. A total of 1,477 (40.6% of 3,624) were told about noncalcified lung nodules on the initial screening and, before repeat screening, 821 (55.6% of 1,477, 22.5% of 3,642) obtained one or more subsequent diagnostic imaging studies (CT, positron emission tomography [PET], or PET-CT). Tracking identified 80 subjects with lung cancer, including 53 subjects with tumor seen at initial screening. In all, 36 subjects (1.0% of the 3,642 screened), referred for abnormalities on either the initial or repeat screening, had a major thoracic surgical procedure (thoracotomy, video-assisted thoracoscopic surgery [VATS], median sternotomy, or mediastinoscopy) leading to a noncancer final diagnosis. Out of 82 subjects with thoracotomy or VATS to exclude malignancy in a lung nodule, 28 (34.1%) received a noncancer final diagnosis. Forty of 69 (58%) subjects with non-small cell lung cancer had stage I disease at diagnosis.Conclusions: Though leading to the discovery of early stage lung cancer, CT screening also led to many diagnostic follow-up procedures, including major thoracic surgical procedures with noncancer outcomes. [ABSTRACT FROM AUTHOR]

Rationale: To study the relationship between emphysema and/or airflow obstruction and lung cancer in a high-risk population.Objective: 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).Methods: 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.Measurements and Main Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

The 2005 Dietary Guidelines for Americans include quantitative recommendations for 2 eating patterns, the USDA Food Guide and the Dietary Approaches to Stop Hypertension (DASH) Eating Plan, to promote optimal health and reduce disease risk. A Mediterranean dietary pattern has also been promoted for health benefits. Our objective was to determine whether adherence to the USDA Food Guide recommendations, the DASH Eating Plan, or a Mediterranean dietary pattern is associated with reduced risk of distal colorectal adenoma. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, men and women aged 55-74 y were screened for colorectal cancer by sigmoidoscopy at 10 centers in the U.S. After adjusting for potential confounders, men who most complied with the USDA Food Guide recommendations had a 26% reduced risk of colorectal adenoma compared with men who least complied with the recommendations (OR USDA score >or= 5 vs. or= 5 vs. or= 5 vs.

Summary: The purpose of this study was to generate stable cell cultures from head and neck squamous cell carcinomas (HNSCC), and retrospectively analyze the factors associated with successful cell line establishment. Fifty-two HNSCC cell lines were isolated from a series of 199 tumors collected between 1992 and 1997 at the University of Pittsburgh Medical Center. Cell lines were characterized at the molecular and cellular level to determine the features associated with cell line formation. Successful cell line formation was dependent on multiple factors, including gene amplification involving chromosomal band 11q13, local and/or regional involvement of lymph nodes, and alcohol usage. The establishment of HNSCC cell lines enriches the resources available for cancer research. Our findings indicate that generation of stable cell lines from HNSCC is biased towards tumors with a poor prognosis. Our 52 stable lines comprise one of the largest series of HNSCC cell lines in the literature, with complete demographic, histopathologic, clinical, and survival data. [Copyright &y& Elsevier]

Background: Epidemiological studies indicate that some characteristics of lung cancer among never-smokers significantly differ from those of smokers. Aberrant promoter methylation and mutations in some oncogenes and tumor suppressor genes are frequent in lung tumors from smokers but rare in those from never-smokers. In this study, we analyzed promoter methylation in the ras-association domain isoform A (RASSF1A) and the death-associated protein kinase (DAPK) genes in lung tumors from patients with primarily non-small cell lung cancer (NSCLC) from the Western Pennsylvania region. We compare the results with the smoking status of the patients and the mutation status of the K-ras, p53, and EGFR genes determined previously on these same lung tumors. Methods: Promoter methylation of the RASSF1A and DAPK genes was analyzed by using a modified two-stage methylation-specific PCR. Data on mutations of K-ras, p53, and EGFR were obtained from our previous studies. Results: The RASSF1A gene promoter methylation was found in tumors from 46.7% (57/122) of the patients and was not significantly different between smokers and never-smokers, but was associated significantly in multiple variable analysis with tumor histology (p = 0.031) and marginally with tumor stage (p = 0.063). The DAPK gene promoter methylation frequency in these tumors was 32.8% (40/122) and did not differ according to the patients' smoking status, tumor histology, or tumor stage. Multivariate analysis adjusted for age, gender, smoking status, tumor histology and stage showed that the frequency of promoter methylation of the RASSF1A or DAPK genes did not correlate with the frequency of mutations of the K-ras, p53, and EGFR gene. Conclusion: Our results showed that RASSF1A and DAPK genes' promoter methylation occurred frequently in lung tumors, although the prevalence of this alteration in these genes was not associated with the smoking status of the patients or the occurrence of mutations in the K-ras, p53 and EGFR genes, suggesting each of these events may represent independent event in non-small lung tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: It is possible that high-glycemic-load diets, through their hyperinsulinemic effects, can increase the risk of colorectal cancer. Objective: We analyzed data from a cancer screening study to determine whether persons with high-glycemic-load diets would be at an increased risk of distal adenomas. Design: We included subjects with no prior adenoma or cancer from the Prostate, Lung, Colorectal, and Ovarian screening trial and whose results from flexible sigmoidoscopy exams indicated either no lesions (n = 34 817) or ⩾1 distal adenoma (n = 3696). We used a 137-item food-frequency questionnaire to assess usual dietary intake over the preceding 12 mo. Using logistic regression analysis, we calculated, separately for men and women, prevalence odds ratios (ORs) and 95% CIs of sigmoidoscopy-detected, distal adenomas for quintiles of energy-adjusted dietary carbohydrate, glycemic index, and glycemic load. Results: ORs decreased with increasing intakes of carbohydrate for both the men and the women in unadjusted models, but these associations were attenuated in multivariate-adjusted models. Among the men, the association remained significant after adjustment (OR: 0.71; 95% CI 0.60, 0.84; P for trend < 0.0001), but in the women it did not (OR: 0.89; 95% CI: 0.73, 1.10; P for trend = 0.30). The results for glycemic index showed no associations in either men or women. Results for glycemic load closely mirrored those for carbohydrate. Conclusion: Despite expectations that increasing glycemic load and glycemic index would increase the risk of adenoma, we observed no association in women and even an inverse association in men. [ABSTRACT FROM AUTHOR]

Context: The necessary frequency of endoscopic colorectal cancer screening after a negative examination is uncertain.Objective: To examine the yield of adenomas and cancer in the distal colon found by repeat flexible sigmoidoscopy (FSG) 3 years after a negative examination.Design, Setting, and Participants: Participants were drawn from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), a randomized, controlled community-based study of cancer screening. The mean (SD) age was 65.7 (4.0) years at study entry (1993-1995) and 61.6% were men. Individuals underwent screening FSG at baseline and at 3 years as part of the protocol and were referred to their personal physicians for further evaluation of screen-detected abnormalities. Results from subsequent diagnostic evaluations were tracked in a standardized fashion. Of 11 583 eligible for repeat screening FSG 3 years after an initial negative examination, 9317 (80.4%) returned.Main Outcome Measures: Polyp or mass detection in distal colon at year 3 repeat FSG; incidence of adenoma or cancer in distal colon at year 3 examination; determination of reason for detection (increased depth of insertion or improved preparation at the year 3 examination or detection in a previously examined area).Results: A total of 1292 returning participants (13.9%) had a polyp or mass detected by FSG 3 years after the initial examination. In the distal colon, 3.1% (292/9317) were found to have an adenoma or cancer. The incidence of advanced adenoma (n = 72) or cancer (n = 6) in the distal colon was 78 (0.8%) of 9317. Of individuals with advanced distal adenomas detected at the year 3 examination, 80.6% (58/72) had lesions found in a portion of the colon that had been adequately examined at the initial sigmoidoscopy.Conclusions: Repeat FSG 3 years after a negative examination will detect advanced adenomas and distal colon cancer. Although the overall percentage with detected abnormalities is modest, these data raise concern about the impact of a prolonged screening interval after a negative examination. [ABSTRACT FROM AUTHOR]

The article presents a research of stage screening behavior for colorectal cancer using transtheoretical model. The object of the study is to describe the colorectal cancer (CRC)-screening behavior of two lower income communities near Pittsburgh, Pennsylvania. The individuals were characterized according to their stage of readiness to engage in two screening tests, the fecal occult blood test (FOBT) and the flexible sigmoidoscopy (FSG) test. About 414 respondents were surveyed by telephone and revealed that they showed associations between FOBT or FSG behavioral stage including age, recent doctor checkup, history of antigen blood testing and chronic need for prescription medications.

Recent studies have suggested that bone mineral density (BMD) is related to risk of breast cancer in elderly women. This study investigated whether the level of breast cancer risk associated with BMD in women with a positive family history of breast cancer is different from that in women without a family history of breast cancer. Radial and calcaneus BMD were measured at baseline (1986–1988) in 7, 250 elderly white women enrolled in the Study of Osteoporotic Fractures, and initial breast cancer status was ascertained at year 1 of follow-up. After a mean of 3.2 years of additional follow-up, 104 incident breast cancer cases, 20 of which appeared in women with a family history of breast cancer, were identified and confirmed by medical record review. Modification of the BMD effect by family history status was assessed by inclusion of interaction terms in proportional hazards regression models. Among women without a family history of breast cancer, those with a proximal radius BMD in the highest fertile were at a 1.48-fold increased risk compared with women in the lowest tertile; among women with a positive family history of breast cancer, those with highest fertile BMD were at a 3.41–fold increased risk compared with women in the lowest tertile. These results suggest that the association between BMD and breast cancer may be different in subgroups of women defined by family history. Am J Epidemiol 1998; 148: 22–9. [ABSTRACT FROM PUBLISHER]

Proto-oncogenes are genes coding for factors involved in cellular growth, reproduction, and differentiation. Cancer results through mutations of proto-oncogenes or through other mechanisms involving the products of proto-oncogenes. This study asks whether serum proteins immunologically related to the products of proto-oncogenes distinguish older men and women who manifest a new cancer during a 2-year follow-up. The authors conducted a nested case-control study that involved 248 men and women selected from a larger group of older (age ≥65 years) healthy volunteers in a randomized clinical trial of preventive clinical services. Study subjects included 37 with a fatal cancer, 59 non-fatal breast, prostate, colon, or lung cancer, 58 hospitalized with at least one discharge diagnosis that coded to benign neoplasia (International Classification of Diseases, 9th Revision codes 210-239), and 94 randomly selected controls. Using seven monoclonal antibodies prepared against ras, ertb-B, FES, myb, and SIS polypeptide sequences, immunoblots detected 17 proteins in serum collected from subjects before the clinical recognition of cancer. Five oncogene-related serum proteins appeared to distinguish older persons who manifested fatal (but not non-fatal) cancer over a brief (2-year) follow-up. Older persons hospitalized with benign neoplasia also had higher levels of these serum proteins. Relative to the 94 control subjects, a 52,000 dalton SIS-related protein (odd ratio (OR) = 5.9, 95% confidence interval (CI) 1.4-24.9) and a 35,000 dalton k-ras-related protein (OR = 11.3, 95% CI 1.2-104) were particularly common in serum from the 37 subjects who manifested a fatal cancer. [ABSTRACT FROM AUTHOR]

Objectives: Evidence is accumulating supporting the use of screening for colorectal cancer. Patients at higher risk for colorectal career are more likely to benefit from screening. Women with breast, endometrial, or ovarian cancer are often classified as at high risk for subsequent colorectal cancer, and are urged to undergo screening, but the basis for this is uncertain. Methods: We performed a meta-analysis of published data to assess the risk of colorectal cancer after these cancers. Results: Based on 154,270 women and 779,251 person-yr of observation (PYO) after breast cancer, 37,266 women and 229,498 PYO after endometrial cancer, and 41,366 women and 126,688 PYO after ovarian cancer, the age-adjusted relative risk (95%CI) for colorectal cancer after breast cancer was 1.1 (1.07, 1.19), after endometrial cancer 1.4 (1.32, 1.55), and after ovarian cancer 1.6 (1.40, 1.80). Conclusions: 1) Women with a history of breast, endometrial, or ovarian cancer are at a statistically significant increased risk for subsequent colorectal cancer. 2) Women with a history of endometrial or ovarian cancer are at higher risk than are women with breast cancer, but ascertainment bias from heightened medical surveillance after the diagnosis of a gynecologic malignancy may contribute to this observed increase in risk. 3) The association between these cancers and colorectal cancer suggests common etiologic factors, either environmental or genetic, but the degree of increased risk is small. [ABSTRACT FROM AUTHOR]