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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 (P(interaction) = .81), pretrial PSA testing (P(interaction) = .52), and comorbidity (P(interaction) = .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 AUTHOR]

Context: The effect on mortality of screening for lung cancer with modern chest radiographs is unknown.Objective: To evaluate the effect on mortality of screening for lung cancer using radiographs in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.Design, Setting, and Participants: Randomized controlled trial that involved 154,901 participants aged 55 through 74 years, 77,445 of whom were assigned to annual screenings and 77,456 to usual care at 1 of 10 screening centers across the United States between November 1993 and July 2001. The data from a subset of eligible participants for the National Lung Screening Trial (NLST), which compared chest radiograph with spiral computed tomographic (CT) screening, were analyzed.Intervention: Participants in the intervention group were offered annual posteroanterior view chest radiograph for 4 years. Diagnostic follow-up of positive screening results was determined by participants and their health care practitioners. Participants in the usual care group were offered no interventions and received their usual medical care. All diagnosed cancers, deaths, and causes of death were ascertained through the earlier of 13 years of follow-up or until December 31, 2009.Main Outcome Measures: Mortality from lung cancer. Secondary outcomes included lung cancer incidence, complications associated with diagnostic procedures, and all-cause mortality.Results: Screening adherence was 86.6% at baseline and 79% to 84% at years 1 through 3; the rate of screening use in the usual care group was 11%. Cumulative lung cancer incidence rates through 13 years of follow-up were 20.1 per 10,000 person-years in the intervention group and 19.2 per 10,000 person-years in the usual care group (rate ratio [RR]; 1.05, 95% CI, 0.98-1.12). A total of 1213 lung cancer deaths were observed in the intervention group compared with 1230 in usual care group through 13 years (mortality RR, 0.99; 95% CI, 0.87-1.22). Stage and histology were similar between the 2 groups. The RR of mortality for the subset of participants eligible for the NLST, over the same 6-year follow-up period, was 0.94 (95% CI, 0.81-1.10).Conclusion: Annual screening with chest radiograph did not reduce lung cancer mortality compared with usual care.Trial Registration: clinicaltrials.gov Identifier: NCT00002540. [ABSTRACT FROM AUTHOR]

Some studies of brain cancer have found an excess risk for farmers. The National Institute for Occupational Safety and Health previously found no increased glioma risk for ever (vs. never) being exposed to pesticides on a farm among 798 cases and 1,175 population-based controls (adult (ages 18-80 years) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin). For this analysis (1995-1998), 288 cases and 474 controls (or their proxies) who had lived on farms at age 18 years or after were asked about exposure to crops, livestock, and farm tasks. Logistic regression was used to calculate odds ratios adjusted for age, age group, sex, state, and education. Never immediately washing up (adjusted odds ratio (OR) = 3.08, 95% confidence interval (CI): 1.78, 5.34) or changing clothes (OR = 2.84, 95% CI: 1.04, 7.78) after applying pesticides was associated with increased glioma risk. Living on a farm on which corn, oats, soybeans, or hogs were raised was associated with decreased risk (corn-OR = 0.37, 95% CI: 0.20, 0.69; oats-OR = 0.63, 95% CI: 0.40, 1.00; soybeans-OR = 0.69, 95% CI: 0.48, 0.98; hogs-OR = 0.63, 95% CI: 0.43, 0.93). Negative associations may be due to chance or a 'healthy farmer' effect. Farmers' increased risk of glioma may be due to work practices, other activities, or an inverse association with allergies (reported by other investigators). [ABSTRACT FROM AUTHOR]

The project goal was to collaborate with veterinarians in delivering skin cancer information to a farming population. Two interventions and a control were utilized: in nine Wisconsin counties veterinarians delivered education materials as part of routine dairy herd health visits, veterinarians in nine additional counties provided client lists so education materials could be mailed, and veterinarians in nine control counties provided client lists but farmers received no education materials. A questionnaire was administered by phone to a random sample of farmers in each group, assessing knowledge, sun protection attitudes and behaviors, acceptance of veterinarians in a human health education role. Farmers responded quite favorably to veterinarians in this role. Veterinarians can he regarded as useful agents to disseminate health information to isolated rural populations. [ABSTRACT FROM AUTHOR]

Cumulative sun exposure has been linked to about 95 percent of all skin cancers. Farmers and their families, by nature of their occupations, are exposed to an abundance of sun over a long period of time and, therefore, are at an increased risk for skin cancer. Because education is known to be a primary means of health, Future Farmers of America (FFA) peer facilitators (teen educators) provided third graders in rural communities sun protection education with the hope that the message would reach the entire family. The FFA facilitators (n = 217) from 39 FFA organizations throughout Wisconsin were trained with skin cancer and sun protection information. The FFA facilitators then gave presentations on sun protection to third graders (n = 2,007) in their school districts. Control schools included 57 facilitators and 669 third graders. Evaluation involved pre-, post-, and six-month follow-up surveys testing knowledge gained by the third graders. Students who correctly responded to a question on the post-survey after incorrectly answering it on the pre-survey were said to have had a knowledge gain for that question. By using chi-square tests, the intervention group demonstrated a statistically significant (P < 0.001) higher proportion of students experiencing knowledge gain than did the control group from pre- to post-surveys for nine of the 10 questions. Summary statistics were used to describe the study population. In addition to skin cancer knowledge questions, the survey of facilitators included sun protection behavior and attitude questions. This intervention was able to use peer educators as instructors to demonstrate knowledge gain in the youths of the target population. The pilot project materials costs were +0.55 per third grade student and +3.50 per facilitator. Using a school-based organization such as FFA provided a cost-effective means of reaching the rural population. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to measure the occurrence and natural history of simple ovarian cysts in a cohort of older women.Study Design: Simple cysts were ascertained among a cohort of 15,735 women from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial through 4 years of transvaginal ultrasound screening.Results: Simple cysts were seen in 14% of women the first time that their ovaries were visualized. The 1-year incidence of new simple cysts was 8%. Among ovaries with 1 simple cyst at the first screen, 54% retained 1 simple cyst, and 32% had no cyst 1 year later. Simple cysts did not increase risk of subsequent invasive ovarian cancer.Conclusion: Simple ovarian cysts are fairly common among postmenopausal women, and most cysts appear stable or resolve by the next annual examination. These findings support recent recommendations to follow unilocular simple cysts in postmenopausal women without intervention. [ABSTRACT FROM AUTHOR]

Objectives: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents--carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1--trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. Methods Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites., Results: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma., Conclusions: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology.

Background: Understanding glioma etiology requires determining which environmental factors are associated with glioma. Upper Midwest Health Study case-control participant work histories collected 1995-1998 were evaluated for occupational associations with glioma. "Exposures of interest" from our study protocol comprise our a priori hypotheses., Materials and Methods: Year-long or longer jobs for 1,973 participants were assigned Standard Occupational Classifications (SOC) and Standard Industrial Classifications (SIC). The analysis file includes 8,078 SIC- and SOC-coded jobs. For each individual, SAS 9.2 programs collated employment with identical SIC-SOC coding. Distributions of longest "total employment duration" (total years worked in jobs with identical industry and occupation codes, including multiple jobs, and non-consecutive jobs) were compared between cases and controls, using an industrial hygiene algorithm to group occupations., Results: Longest employment duration was calculated for 780 cases and 1,156 controls. More case than control longest total employment duration was in the "engineer, architect" occupational group [16 cases, 10 controls, odds ratio (OR) 2.50, adjusted for age group, sex, age and education, 95% confidence interval (CI) 1.12-5.60]. Employment as a food processing worker [mostly butchers and meat cutters] was of borderline significance (27 cases, 21 controls, adjusted OR: 1.78, CI: 0.99-3.18)., Conclusions: Among our exposures of interest work as engineers or as butchers and meat cutters was associated with increased glioma risk. Significant associations could be due to chance, because of multiple comparisons, but similar findings have been reported for other glioma studies. Our results suggest some possible associations but by themselves could not provide conclusive evidence., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To quantify outcomes of individuals diagnosed and treated for prostate cancer in a single institution., Design: Retrospective electronic chart abstraction., Setting: Marshfield Clinic, the largest private multispecialty group practice in Wisconsin, and one of the largest in the United States, provides health care services annually to approximately 385,000 unique patients through 1.8 million annual patient encounters., Participants: Individuals within the Marshfield Clinic cancer registry who had been diagnosed with prostate cancer between 1960 and 2009., Methods: Electronic chart abstraction from the cancer registry and the electronic medical record was conducted (N=6,181). Data abstracted included age at diagnosis; stage and grade of tumor; prostate specific antigen (PSA) values before, at, and after diagnosis; initial cancer treatment; follow-up time; subsequent cancer treatments; evidence of metastasis; age of death; and cause of death, if known., Results: The average age of prostate cancer diagnosis has decreased from 70-71 years in the 1960's and 1970's to an average age at diagnosis of 67 years in the 2000's (P<0.001). This decrease in age occurred within the decades of implementation of PSA screening. Approximately 74% of men diagnosed with prostate cancer within the PSA screening era had at least one PSA test, and the presence of a PSA test did not appear to change treatment outcome. Age, grade, and stage were the biggest predictors of prostate cancer outcome. There was no difference in event-free survival between current treatment types (radical prostatectomy, brachytherapy, photon treatment, or intensity-modulated radiation therapy) (2003 or later) when stratified by age (greater than 85%, 5-year event-free survival P=0.85); however, more events occurred with older external beam radiation treatment regimens (1993-2003) (70% to 75%, 5-year event-free survival P=0.001)., Conclusion: Individuals diagnosed and treated for prostate cancer within the Marshfield Clinic comprehensive care setting follow national trends with a decreased age of diagnosis since the advent of PSA screening. Outcomes for individuals treated within the Clinic system are also comparable to national trends.

Background: The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality., Methods: From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained., Results: Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81)., Conclusions: Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.).

Background: An excess incidence of brain cancer in farmers has been noted in several studies. The National Institute for Occupational Safety and Health developed the Upper Midwest Health Study (UMHS) as a case-control study of intracranial gliomas and pesticide uses among rural residents. Previous studies of UMHS participants, using "ever-never" exposure to farm pesticides and analyzing men and women separately, found no positive association of farm pesticide exposure and glioma risks. The primary objective was to determine if quantitatively estimated exposure of pesticide applicators was associated with an increased risk of glioma in male and female participants., Methods: The study included 798 histologically confirmed primary intracranial glioma cases (45 % with proxy respondents) and 1,175 population-based controls, all adult (age 18-80) non-metropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. The analyses used quantitatively estimated exposure from questionnaire responses evaluated by an experienced industrial hygienist with 25 years of work on farm pesticide analyses. Odds ratios (ORs) and 95 % confidence intervals (CIs) using unconditional logistic regression modeling were calculated adjusting for frequency-matching variables (10-year age group and sex), and for age and education (a surrogate for socioeconomic status). Analyses were separately conducted with or without proxy respondents., Results: No significant positive associations with glioma were observed with cumulative years or estimated lifetime cumulative exposure of farm pesticide use. There was, a significant inverse association for phenoxy pesticide used on the farm (OR 0.96 per 10 g-years of cumulative exposure, CI 0.93-0.99). No significant findings were observed when proxy respondents were excluded. Non-farm occupational applicators of any pesticide had decreased glioma risk: OR 0.72, CI 0.52-0.99. Similarly, house and garden pesticide applicators had a decreased risk of glioma: OR 0.79, CI 0.66-0.93, with statistically significant inverse associations for use of 2,4-D, arsenates, organophosphates, and phenoxys., Conclusions: These results are consistent with our previous findings for UMHS of reported farm pesticide exposure and support a lack of positive association between pesticides and glioma.

We tested the hypothesis that genes involved in the alcohol oxidation pathway modify the association between alcohol intake and breast cancer. Subjects were women aged 55-74 at baseline from the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident breast cancers were identified through annual health surveys. Controls were frequency matched to cases by age and year of entry into the trial. A self-administered food frequency questionnaire queried frequency and usual serving size of beer, wine or wine coolers, and liquor. Three SNPs in genes in the alcohol metabolism pathway were genotyped: alcohol dehydrogenase 2, alcohol dehydrogenase 3, and CYP2E1. The study included 1,041 incident breast cancer cases and 1,070 controls. In comparison to non-drinkers, the intake of any alcohol significantly increased the risk of breast cancer, and this risk increased with each category of daily alcohol intake (OR 2.01, 95% CI 1.14, 3.53) for women who drank three or more standard drinks per day. Stratification by genotype revealed significant gene/environment interactions. For the ADH1B gene, there were statistically significant associations between all levels of alcohol intake and risk of breast cancer (all OR > 1.34 and all lower CI > 1.01), while for women with the GA or AA genotype, there were no significant associations between alcohol intake and risk of breast cancer. Alcohol intake, genes involved in alcohol metabolism and their interaction increase the risk of breast cancer in post-menopausal women. This information could be useful for primary care providers to personalize information about breast cancer risk reduction.

Retinol is one of the most biologically active forms of vitamin A and is hypothesized to influence a wide range of human diseases including asthma, cardiovascular disease, infectious diseases and cancer. We conducted a genome-wide association study of 5006 Caucasian individuals drawn from two cohorts of men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We identified two independent single-nucleotide polymorphisms associated with circulating retinol levels, which are located near the transthyretin (TTR) and retinol binding protein 4 (RBP4) genes which encode major carrier proteins of retinol: rs1667255 (P =2.30× 10(-17)) and rs10882272 (P =6.04× 10(-12)). We replicated the association with rs10882272 in RBP4 in independent samples from the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that included 3792 women and 504 men (P =9.49× 10(-5)), but found no association for retinol with rs1667255 in TTR among women, thus suggesting evidence for gender dimorphism (P-interaction=1.31× 10(-5)). Discovery of common genetic variants associated with serum retinol levels may provide further insight into the contribution of retinol and other vitamin A compounds to the development of cancer and other complex diseases.

Although severe immune dysregulation is an established risk factor for non-Hodgkin lymphoma (NHL), it is unclear whether subclinical immune system function influences lymphomagenesis. To address this question, we conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to investigate whether circulating levels of cytokines and other immune markers are associated with future risk of NHL. Selected cytokines [interleukin (IL)-4, IL-6, IL-10, and TNF-α] and other immune markers [soluble TNF receptor 1 (sTNF-R1), sTNF-R2, C-reactive protein, and sCD27] were measured in prediagnostic serum specimens from 297 incident NHL cases and 297 individually matched controls. ORs and 95% confidence intervals (CI) relating quartiles of analyte concentration to NHL risk were calculated by using conditional logistic regression. Statistically significant associations with increased NHL risk were observed for elevated serum levels of sTNF-R1 (quartile 4 vs. quartile 1: OR = 1.7, 95% CI: 1.1-2.8; P(trend) = 0.02) and sCD27 (OR = 5.3, 95% CI: 2.9-9.4; P(trend) < 0.0001). These associations remained in analyses of cases diagnosed longer than 6 years following blood collection (sTNF-R1: OR = 2.1, 95% CI: 1.0-4.0, P(trend) = 0.01; sCD27: OR = 4.1, 95% CI: 1.9-8.5, P(trend) = 0.0001). Elevated levels of IL-10, TNF-α and sTNF-R2 were also significantly associated with increased risk of NHL overall; however, these associations weakened with increasing time from blood collection to case diagnosis and were null for cases diagnosed longer than 6 years postcollection. Our findings for sTNF-R1 and sCD27, possible markers for inflammatory and B-cell stimulatory states, respectively, support a role for subclinical inflammation and chronic B-cell stimulation in lymphomagenesis., (©2011 AACR.)

Context: Screening for ovarian cancer with cancer antigen 125 (CA-125) and transvaginal ultrasound has an unknown effect on mortality., Objective: To evaluate the effect of screening for ovarian cancer on mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial., Design, Setting, and Participants: Randomized controlled trial of 78,216 women aged 55 to 74 years assigned to undergo either annual screening (n = 39,105) or usual care (n = 39,111) at 10 screening centers across the United States between November 1993 and July 2001. Intervention The intervention group was offered annual screening with CA-125 for 6 years and transvaginal ultrasound for 4 years. Participants and their health care practitioners received the screening test results and managed evaluation of abnormal results. The usual care group was not offered annual screening with CA-125 for 6 years or transvaginal ultrasound but received their usual medical care. Participants were followed up for a maximum of 13 years (median [range], 12.4 years [10.9-13.0 years]) for cancer diagnoses and death until February 28, 2010., Main Outcome Measures: Mortality from ovarian cancer, including primary peritoneal and fallopian tube cancers. Secondary outcomes included ovarian cancer incidence and complications associated with screening examinations and diagnostic procedures., Results: Ovarian cancer was diagnosed in 212 women (5.7 per 10,000 person-years) in the intervention group and 176 (4.7 per 10,000 person-years) in the usual care group (rate ratio [RR], 1.21; 95% confidence interval [CI], 0.99-1.48). There were 118 deaths caused by ovarian cancer (3.1 per 10,000 person-years) in the intervention group and 100 deaths (2.6 per 10,000 person-years) in the usual care group (mortality RR, 1.18; 95% CI, 0.82-1.71). Of 3285 women with false-positive results, 1080 underwent surgical follow-up; of whom, 163 women experienced at least 1 serious complication (15%). There were 2924 deaths due to other causes (excluding ovarian, colorectal, and lung cancer) (76.6 per 10,000 person-years) in the intervention group and 2914 deaths (76.2 per 10,000 person-years) in the usual care group (RR, 1.01; 95% CI, 0.96-1.06)., Conclusions: Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality. Diagnostic evaluation following a false-positive screening test result was associated with complications. Trial Registration clinicaltrials.gov Identifier: NCT00002540.

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.

Previous research has indicated that treatment staff often underestimate the informational needs of cancer patients. In this study, the authors determined the total number of information sources obtained and used to influence treatment decisions, and the clinical and demographic factors associated with the use of specific sources of information in cancer patients. Participants were identified by the statewide cancer registry and diagnosed in 2004 with breast, colorectal, lung, or prostate cancer. A self-administered mailed questionnaire elicited cancer treatments, demographics, and information sources used to make treatment decisions. Of those surveyed, 1,784 (66%) participated and responded to all questions regarding information use. Over 69% of study participants reported obtaining information from a source other than the treatment staff. Significant predictors of using additional information sources included younger age, higher income, higher education, complementary and alternative medicine (CAM) use, and reporting shared decision making (all p values <.01). Participants with a college degree were more likely to use the Internet (OR 3.7; 95% CI 1.5-9.0) and scientific research reports (OR 3.3; 95% CI 1.6-6.9) to influence treatment decisions compared with those without a high school degree. Support group use to influence treatment decisions was not associated with socioeconomic variables but did vary by cancer type and CAM use. The sources of information study participants obtained and used to influence treatment decisions varied strongly by socioeconomic and demographic variables. These findings provide a deeper understanding of the information needs of cancer patients and have implications for dissemination strategies that can minimize disparities in access to cancer information.

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 >or=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 >or=2 surveillance examinations versus 26.9% for those with >or=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 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program., Methods: Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period., Results: After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%-61.0%) for men, and 48.8% (95% CI, 48.1%-49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%-29.3%) for men and 22.1% (95% CI, 21.4%-22.7%) for women., Conclusions: For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening.

Vitamin A (retinol) plays a key role in the regulation of cell growth and differentiation, and has been studied as a potential chemopreventive agent for prostate cancer. However, findings from epidemiologic studies on the association between circulating retinol concentrations and the risk of prostate cancer are inconsistent. We examined whether serum concentrations of retinol were associated with the risk of prostate cancer in a nested case-control study using 692 prostate cancer cases and 844 matched controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We estimated the risk of prostate cancer using multivariate, conditional logistic regression to calculate odds ratios and 95% confidence intervals for overall prostate cancer and aggressive disease (stage III or IV or Gleason >7; n = 269). Serum retinol concentrations were not associated with overall prostate cancer risk; however, the highest versus lowest concentrations of serum retinol were associated with a 42% reduction in aggressive prostate cancer risk (P(trend) = 0.02), with the strongest inverse association for high-grade disease (Gleason sum >7; odds ratio, 0.52; 95% confidence interval, 0.32-0.84; P(trend) = 0.01). Our results suggest that higher circulating concentrations of retinol are associated with a decreased risk of aggressive prostate cancer. Further research is needed to better understand the significance of elevations in serum retinol concentrations and the possible biological mechanisms through which retinol affects prostate cancer.

Background: The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality., Methods: From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained., Results: In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings., Conclusions: After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.), (2009 Massachusetts Medical Society)

Background: Few risk factors have been implicated in pancreatic cancer etiology. Alcohol has been theorized to promote carcinogenesis. However, epidemiologic studies have reported inconsistent results relating alcohol intake to pancreatic cancer risk., Methods: We conducted a pooled analysis of the primary data from 14 prospective cohort studies. The study sample consisted of 862,664 individuals among whom 2,187 incident pancreatic cancer cases were identified. Study-specific relative risks and 95% confidence intervals were calculated using Cox proportional hazards models and then pooled using a random effects model., Results: A slight positive association with pancreatic cancer risk was observed for alcohol intake (pooled multivariate relative risk, 1.22; 95% confidence interval, 1.03-1.45 comparing >or=30 to 0 grams/day of alcohol; P value, test for between-studies heterogeneity=0.80). For this comparison, the positive association was only statistically significant among women although the difference in the results by gender was not statistically significant (P value, test for interaction=0.19). Slightly stronger results for alcohol intake were observed when we limited the analysis to cases with adenocarcinomas of the pancreas. No statistically significant associations were observed for alcohol from wine, beer, and spirits comparing intakes of >or=5 to 0 grams/day. A stronger positive association between alcohol consumption and pancreatic cancer risk was observed among normal weight individuals compared with overweight and obese individuals (P value, test for interaction=0.01)., Discussion: Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day.

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.

The Satisfaction with Life Domains Scale for Cancer (SLDS-C) is a brief self-report measure of quality of life that uses a familiar and easily understood graphic response format of smiling and frowning faces. This article explores the factor structure and further examines the validity of the SLDS-C compared with another cancer specific quality-of-life measure, the Functional Assessment of Cancer Therapy Scale-General (FACT-G), in a sample of patients with a variety of cancer diagnoses. A self-administered questionnaire containing the SLDS-C and the FACT-G was completed by 352 adult cancer survivors who were at various points post diagnosis. Three SLDS-C factor subscales were derived from analyses of these data: "Life as a Whole," "Daily Activities," and "Social Relationships." Evidence for the concurrent validity of the SLDS-C is presented, including its correlation with the total score of the FACT-G (r = .76) and its correlation with subscale scores of this widely used cancer quality-of-life measure. The SLDS-C has a high level of internal consistency (alpha = .94), and differences in SLDS-C total scores were found for time since diagnosis, number of diagnoses, spread of disease, type of cancer, and treatment status.

Since several studies indicated that farmers and agricultural workers had an excess risk of brain cancer, the National Institute for Occupational Safety and Health initiated the Upper Midwest Health Study to examine risk of intracranial glioma in the non-metropolitan population. This population-based, case-control study evaluated associations between gliomas and rural and farm exposures among adults (ages 18 to 80) in four upper midwestern states (Iowa, Michigan, Minnesota, Wisconsin). At diagnosis/selection, participants lived in non-metropolitan counties where the largest population center had fewer than 250,000 residents. Cases were diagnosed 1 January 1995 through 31 January 1997. Over 90% of 873 eligible ascertained cases and over 70% of 1670 eligible controls consented to participate. Participants and nonparticipants, evaluated for "critical questions" on main and refusant questionnaires, differed significantly in farming and occupational experience, ethnicity, education, and lifestyle. The 1,175 controls were more likely than the 798 cases to have reported ever drinking alcohol (77% vs. 73%, adjusted odds ratio (OR) 0. 73, 95% confidence interval (CI) 0.59-0.92) and having had panoramic dental x-rays (34% vs. 29%, OR 0. 75, CI 0.61-0.92). Controls spent a greater percentage of their lives in non-metropolitan counties (78% vs. 75%, OR 0.81, CI 0.67-1.09). Among ever-farmers, controls were more likely to have had exposure to farm insecticides (57% vs. 50%, OR 0.75, CI 0.59-0.95) and farm animals (96% vs. 91%, OR 0.48, CI 0.25-0.90). Moving to a farm as an adolescent (ages 11 to 20) vs. as an adult was associated with a greater risk of glioma. In our study sample, farm or rural residence and summary farm exposures were associated with decreased glioma risk. However, nonparticipation by never-farming eligible controls could have affected results. Comparisons of farm chemical exposures may clarify associations between farming and glioma that others have reported.

Clinical studies have reported associations between ovarian stromal hyperplasia and the diagnosis of hormonally related tumors such as endometrial cancer. To assess the hypothesis that characteristics of benign ovaries among postmenopausal women are related to risk for breast, endometrial, and colon cancer, we analyzed systematically collected transvaginal ultrasound data for participants enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Among women without cancer, median ovarian volume declined with age from 1.25 cm3 for women between ages 55 and 59 years to 1.0 cm3 for those between ages 65 and 69 years. African American and Caucasian women had larger median ovarian volumes than Asians. Larger ovarian volume was also associated with the highest quartiles of height and weight and ever having smoked. After adjusting for race, age, parity, body mass, smoking, and hormone use, women with median ovarian volumes >or=3.0 cm3 were at increased risk for breast cancer [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25-3.21). Significant trends of risk with increasing volume were found only for breast and endometrial cancers. We conclude that large ovaries among postmenopausal women may represent a marker of risk for hormonally related tumors. Confirmation of these findings in future studies, including analyses of serum hormone levels and tissues, may provide insights into hormonal carcinogenesis among older women.

An excess incidence of brain cancer in male farmers has been noted in several studies, but few studies have focused on women. The National Institute for Occupational Safety and Health Upper Midwest Health Study evaluated effects of rural exposures for 341 female glioma cases and 528 controls, all adult (18-80 years of age) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. On average, controls lived longer on farms than did cases. After adjusting for age, age group, education, and farm residence, no association with glioma was observed for exposure to arsenicals, benzoic acids, carbamates, chloroacetanilides, dinitroanilines, inorganics, organochlorines, organophosphates, phenoxys, triazines, or urea-based or estrogenic pesticides. An increased risk of glioma was observed for carbamate herbicides but was not statistically significant (odds ratio = 3.0; 95% confidence interval, 0.9-9.5). No association was observed between glioma and exposure to 12 widely used specific pesticides, after adjustment for age, age group, education, and any other pesticide exposure. These results were not affected after exclusion of proxy respondents (43% of cases, 2% of controls). Women were less likely than men to have applied pesticides, but more likely to have laundered pesticide-contaminated clothes. Storing pesticides in the house was associated with a statistically non-significant increased risk. Results show that exposure to pesticides was not associated with an increased risk of intracranial gliomas in women. Other farm-related factors could be etiologic factors and will be discussed in future reports.

Agencies serving the estimated 42,000 to 137,000 migrant and seasonal farmworkers in the Lake States (Wisconsin, Michigan, and Minnesota) face distinct challenges, including inadequate access to farmworker data to address their needs. This project developed and evaluated a geographical information system (GIS) database for compiling and displaying existing farmworker data in the Lake States. A three-step study was conducted in the Lake States: (1) a preliminary resource and needs assessment was conducted among agencies serving farmworkers, (2) a GIS product was created using data available from state agencies, and (3) the GIS product was evaluated by an advisory board of qualified occupational health and safety representatives for appropriateness, applications, and ease of use. Agencies participated by sharing their available farmworker data. The GIS product consisted of a CD-ROM with data displayed in a graphic format and downloadable spreadsheet files consolidated by county demographic, crop, housing, and migrant health clinic information. Evaluators of the GIS product found it to be an accessible, unique clearinghouse for farmworker-related data. The GIS product can become a valuable tool for agencies serving farmworkers and those researching farmworker-related issues. Agencies and health professionals require useful and comprehensive databases to track and serve farmworkers, and a multi-agency partnership using GIS technology could provide this capability. Further research is required with improved definitions and resources to apply the GIS product.

The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and found reduced glioma risk for insecticides (OR = 0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of cases) most CIs included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies.

Objective: Glioma is the most common primary malignant brain tumor in adults, responsible for 75% of adult primary malignant brain tumors, yet aside from its association with ionizing radiation, its etiology is poorly understood. Sex differences in brain tumor incidence suggest that hormonal factors may play a role in the etiology of these tumors, but few studies have examined this association in detail. The objective of this study was to explore the role of reproductive factors in the etiology of glioma in women., Method: As part of a population-based case-control study, histologically confirmed primary glioma cases (n = 341 women) diagnosed between January 1, 1995 and January 31, 1997 were identified through clinics and hospitals in four Midwest U.S. states. Controls (n = 527 women) were randomly selected from lists of licensed drivers and Health Care Finance Administration enrollees. In-person interviews with subjects (81%) or their proxies (19%) collected reproductive history and other exposure information., Results: Glioma risk increased with older age at menarche (P for trend = 0.009) but only among postmenopausal women. Compared with women who never breast-fed, women who breast-fed >18 months over their lifetime were at increased risk of glioma (odds ratio, 1.8; 95% confidence interval, 1.1-2.9). Women who reported using hormones for symptoms of menopause had a decreased risk of glioma compared with women who never used such hormones (odds ratio, 0.7; 95% confidence interval, 0.5-1.1)., Conclusion: These results support the hypothesis that reproductive hormones play a role in the etiology of glioma among women.

Considerable evidence demonstrates that genetic factors are important in the development and aggressiveness of prostate cancer. To identify genetic variants that predispose to prostate cancer we tested candidate SNPs from genomic regions that show linkage to prostate cancer susceptibility and/or aggressiveness, as well as genes that show a significant difference in mRNA expression level between tumor and normal tissue. Cases had histologically verified prostate cancer. Controls were at least 65 years old, never registered a PSA above 2.5 ng/ml, always had digital rectal examinations that were not suspicious for cancer, and have no known family history of prostate cancer. Thirty-nine coding SNPs and nine non-coding SNPs were tested in up to 590 cases and 556 controls resulting in over 40,000 SNP genotypes. Significant differences in allele frequencies between cases and controls were observed for ID3 (inhibitor of DNA binding), p = 0.05, HPN (hepsin), p = 0.009, BCAS1 (breast carcinoma amplified sequence 1), p = 0.007, CAV2 (caveolin 2), p = 0.007, EMP3 (epithelial membrane protein 3), p < 0.0001, and MLH1 (mutL homolog 1), p < 0.0001. SNPs in three of these genes (BCAS1, EMP3 and MLH1) remained significant in an age-matched subsample., (Copyright (c) 2004 S. Karger AG, Basel.)

Prostate cancer is the most frequently diagnosed neoplasia in men and one of the leading causes of cancer-related deaths in men over 60. In an effort to understand the molecular events leading to prostate cancer, we have identified PCAN1 (prostate cancer gene 1) (also known as GDEP), a gene that is highly expressed in prostate epithelial tissue and frequently mutated in prostate tumors. Here we demonstrate its expression in neural retina, and retinoblastoma cell culture but not retinal pigment epithelial cell culture. We further characterize PCAN1 expression in the prostate cell lines RWPE1, RWPE2, and LnCAP FGC. We demonstrate an increase in expression when the cells are grown in the presence of Matrigel, an artificial extracellular basement membrane. Expression was time dependent, with expression observed on d 6 and little or no expression on d 12. Testosterone was not found to increase PCAN1 expression in this culture system. In addition, normal prostate epithelial cells co-cultured with normal prostate stromal cells did not exhibit PCAN1 expression at any time. To definitively locate the transcription initiation sites, we performed restriction-ligase-mediated 5' RACE, to selectively amplify only mRNA with a 5' cap. An initial characterization of the sequence upstream of the initiation sites determined six possible binding sites for the prostate specific regulatory protein NKX3.1 and four potential binding sites for the PPAR/RXR heterodimer that is involved in the control of cell differentiation and apoptosis.

Prostate cancer is the most frequently diagnosed visceral cancer of men, responsible for approximately 40,000 deaths in adult males per year. To identify the genetic causes of prostate cancer, we performed a whole genome scan of affected sib pairs, using DNA markers spaced evenly across the human genome. We demonstrated that regions on chromosomes 1, 4, 5, 7, 8, 11, 16 and 19 might harbor genes that predispose individuals to prostate cancer and may affect tumor growth rate and tumor aggressiveness. Here we present DNA sequence analysis of KIAA 0872 and 17-beta hydroxysteroid dehydrogenase that are located on chromosome 16 within the mapped region, and we demonstrate that neither of these genes carries mutations in the protein coding region or their splice junction sites. These results suggest that these genes are less likely to be associated with the cause of familial prostate cancer.

Although prostate cancer is the second leading cause of cancer death for men in the United States, the genetics of tumor development are poorly understood. Several expressed sequence tagged genes (ESTs) that are expressed predominantly in the prostate have recently been identified, although their role in the development and maintenance of the prostate is unknown. Here, we demonstrate that the gene identified as UNIGENE cluster Hs. 104215, which codes for a message found predominantly in the prostate, may be important in tumor development. We name this gene PCan1 for Prostate Cancer gene 1. Northern blot experiments were performed using RNA isolated from tumor-derived cell lines and human prostate to determine the expression pattern of the gene. DNA sequencing was used to identify mutations that occurred in tumor tissue. By Northern blot analysis, this gene product was not detectable in LNCaP, DU 145, or PC-3 prostate cancer cell lines, although it was readily observed in RNA isolated from total prostate and from dissected central and peripheral regions of prostate. Sequence analysis of genomic DNA from LNCaP, DU 145, or PC-3 cells demonstrated a G/A polymorphism at position 193. Analysis of matched tumor-derived DNA and blood-derived DNA samples from 11 of 13 patients who had undergone a radical prostatectomy and who were homozygous for A in blood-derived DNA demonstrated mutation of position 193 in matched tumor samples resulting in G/A polymorphism. Sixteen additional patient samples were G/A polymorphic in both blood-derived DNA and tumor-derived DNA and two samples were GG in both blood-derived and tumor-derived DNA. Our results suggest that this gene may be a hot spot for mutation in prostate cancer, especially because our radiation hybrid mapping located this gene within a region identified in linkage mapping studies of affected families with prostate cancer. Loss of heterozygosity in prostate tumors has also been reported at the location of PCan1. Further studies to determine the functional role of this candidate tumor suppressor gene are warranted.

Objective: To examine the degree to which variation in place of death is explained by differences in the characteristics of patients, including preferences for dying at home, and by differences in the characteristics of local health systems., Design: We drew on a clinically rich database to carry out a prospective study using data from the observational phase of the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT component). We used administrative databases for the Medicare program to carry out a national cross-sectional analysis of Medicare enrollees place of death (Medicare component)., Setting: Five teaching hospitals (SUPPORT); All U.S. Hospital Referral Regions (Medicare)., Study Populations: Patients dying after the enrollment hospitalization in the observational phase of SUPPORT for whom place of death and preferences were known. Medicare beneficiaries who died in 1992 or 1993., Main Outcome Measures: Place of death (hospital vs non-hospital)., Results: In SUPPORT, most patients expressed a preference for dying at home, yet most died in the hospital. The percent of SUPPORT patients dying in-hospital varied by greater than 2-fold across the five SUPPORT sites (29 to 66%). For Medicare beneficiaries, the percent dying in-hospital varied from 23 to 54% across U.S. Hospital Referral Regions (HRRs). In SUPPORT, variations in place of death across site were not explained by sociodemographic or clinical characteristics or patient preferences. Patient level (SUPPORT) and national cross-sectional (Medicare) multivariate models gave consistent results. The risk of in-hospital death was increased for residents of regions with greater hospital bed availability and use; the risk of in-hospital death was decreased in regions with greater nursing home and hospice availability and use. Measures of hospital bed availability and use were the most powerful predictors of place of death across HRRs., Conclusions: Whether people die in the hospital or not is powerfully influenced by characteristics of the local health system but not by patient preferences or other patient characteristics. These findings may explain the failure of the SUPPORT intervention to alter care patterns for seriously ill and dying patients. Reforming the care of dying patients may require modification of local resource availability and provider routines.

Background: Providing medical services to rural residents results in unique challenges to providers and patients. Cancer screening (CS) and early detection services (EDS) are frequently underutilized with rural residents often presenting with advanced cancer at diagnosis. A comprehensive approach to determine barriers and overcome them constitutes "The Greater Marshfield Experience.", Methods: Focus groups with rural residents determined the greatest barriers to receipt of CS and EDS were distance, cost, time from work and self-reliant behavior. Directives to address these concerns were to keep information simple and provide services at the workplace. In response, Marshfield Clinic and its research division developed a collaborative research partnership with public health agencies (PHA), federally funded government programs and volunteer agencies., Results: In-house activities to remove barriers for providing CS and EDS included the development of a separate screening unit for these activities. Reminder systems were employed to notify patients of the need and availability of preventative services. Co-payments for health screening services were eliminated from the clinic owned health plan. Area residents near poverty level were encouraged to enroll in federally subsidized health plans that promoted and paid for CS and EDS. Federally funded cancer screening studies were implemented that funded breast and cervical cancer screening and evaluated the benefits of screening for prostate, lung, colorectal and ovarian cancers (PLCO). Outreach activities included developing partnerships with local PHA and minority groups and providing mobile screening services to remote areas., Conclusion: Concentrated, collaborative efforts to develop in-house systems and outreach activities resulted in delivery of CS and EDS in remote areas.

Objective: To determine the effect of age on hospital resource use for seriously ill adults, and to explore whether age-related differences in resource use are explained by patients' severity of illness and preferences for life-extending care., Study Design: Prospective cohort study., Setting: Five geographically diverse academic acute care medical centers participating in the SUPPORT Project., Patients: A total of 4301 hospitalized adults with at least one of nine serious illnesses associated with an average 6-month mortality of 50%., Measurements: Resource utilization was measured using a modified version of the Therapeutic Intervention Scoring System (TISS); the performance of three invasive procedures (major surgery, dialysis, and right heart catheter placement); and estimated hospital costs., Results: The median patient age was 65; 43% were female, and 48% died within 6 months. After adjustment for severity of illness, prior functional status, and study site, when compared with patients younger than 50, patients 80 years or older were less likely to undergo major surgery (adjusted odds ratio .46), dialysis (.19), and right heart catheter placement (.59) and had median TISS scores and estimated hospital costs that were 3.4 points and $ 71.61 lower, respectively. These differences persisted after further adjustment for patients' preferences for life-extending care., Conclusions: Compared with similar younger patients, seriously ill older patients receive fewer invasive procedures and hospital care that is less resource-intensive and less costly. This preferential allocation of hospital services to younger patients is not based on differences in patients' severity of illness or general preferences for life-extending care.

The Healthy People 2000-National Health Promotion and Disease Prevention Objectives call for an increase in breast health education to the public to increase women's knowledge about breast cancer and the benefits of screening. A breast health outreach education intervention for community health professionals was designed, implemented, and evaluated. The barriers to continuing education of health professionals of rural areas were addressed. Low-cost, county-based seminars using a comprehensive breast health education curriculum were provided for community health professionals. The intervention demonstrated an increase in a professional's knowledge about breast cancer and breast cancer screening, and an increase in their breast self-examination skills. Six months after intervention, community health professionals reported an increase in the frequency of their breast self-examination performance.

Adult patients (> or = 56 years old) with acute myeloid leukemia (AML) received induction therapy consisting of daunorubicin (60 mg/m2), etoposide (80 mg/m2), and cytarabine (200 mg/m2) daily for 5 days by continuous i.v. infusion (120 hours). The initial protocol was modified so that patients who were not hypoplastic after the first cycle of chemotherapy received a second cycle of treatment, utilizing 30 mg/m2 of daunorubicin/24 hours for 5 days plus etoposide and cytarabine as used in the first cycle. Two courses of consolidation with etoposide and cytarabine at the same dose and schedule were given. Patients were then maintained on cytarabine monthly. Twelve of 29 previously untreated patients (41%) achieved complete remission (CR). Excluding patients with secondary AML, 48% of all patients (11/23) achieved CR, including 56% > or = 70 years old. The median duration of CR was 41 weeks and median survival of CR patients was 54 weeks. Six of 13 patients (46%) with relapsed AML achieved CR. Toxicity in these older adult patients has been mild. Two patients (8%) had severe mucositis and one had severe (bloody) diarrhea. Most patients developed a mild transient asymptomatic rash. Triple infusion chemotherapy (TIC) may be as effective as other chemotherapy regimens for AML in older adults and has acceptable toxicity.

Results from a quasi-experimental project indicate that skin cancer prevention and sun protection education can successfully be promoted by using peer educators. Senior high students (40) facilitated and taught a sun protection curriculum to third-grade students (508) enrolled at the experimental sites. The curriculum's effects were assessed with pre-program, post-program, and 6-month follow-up survey-instruments. The experimental sites using high school (peer) facilitators were effective in conveying knowledge to younger students based on knowledge gained on the post-program surveys. Overall, the intervention group demonstrated a mean improvement of 3.4 questions on the post-program survey, while the control group improved 0.1 questions (p < 0.01). Additional benefits included a knowledge gain by the peer facilitators, a self-reported possible increase in desired behavior change, and an improved attitude about sun protection. Implications for pediatric clinical practice are noted.

Established methods of health promotion for the general population are not as effective with rural populations, in part because conventional health education delivery systems may not penetrate isolated rural areas. In particular, the self-reliant behaviors of farmers make them less likely to seek traditional forms of health care, including health promotional activity. Yet farmers place a great deal of trust in their veterinarian and highly rate veterinarian integrity. Wisconsin veterinarians expressed an interest in the health of their human clients as well as the health of the animals in their care. An education demonstration project was developed to determine farmers' acceptance of veterinarians delivering human health information to their workplace (farms). Thirteen veterinarians who provide services in one north central Wisconsin county delivered skin cancer and sun protection information to farmers as part of their routine herd health checks. Participating farmers reported this to be an acceptable way to receive information about human health issues. This novel method of education delivery may be an effective means to disseminate human health information to difficult-to-reach rural populations.

To respond to major needs expressed by 15 farm family focus group participants, education interventions were designed to overcome barriers to primary prevention for skin cancer. Farmers are at high risk for developing skin cancer because of occupational exposure. In an attempt to increase skin cancer prevention education in a rural population, three demonstration projects were developed and field tested. Projects were designed to overcome barriers defined by the focus groups. One project evaluated a school-based education intervention. A second project evaluated a family-based education intervention. Knowledge gain was the evaluation endpoint of these two projects. Significant knowledge gain was demonstrated for these projects. A third project was designed to deliver skin cancer information directly to farmers using veterinarians. Farmers found this method of delivery acceptable.

The clinical future of hematopoietic growth factors appears promising. They will probably achieve broad clinical application in a wide variety of hematologic disorders. Their use in infectious diseases associated with granulocytopenia and in cancer-treatment regimens as adjuvant agents against myelosuppression and perhaps as stimulants of the natural anti-cancer effects of host cells also seems appropriate.