Prostate, Lung, Colorectal And Ovarian Cancer Screening Trial Research Articles

Abstract 6465: Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Our previous study using the Lovelace Smokers cohort identified early natural menopause (i.e., age at menopause<45 yr), which is a biomarker of ovarian aging, as a risk factor for lung disease and mortality among female smokers. However, most of the associations reported in female smokers with natural menopause were not observed in those with surgical menopause, (a mixed group of subjects with bilateral oophorectomy or hysterectomy without bilateral oophorectomy). Females with bilateral oophorectomy lose ovarian estrogen and progesterone production, while females with hysterectomy, +/- unilateral oophorectomy, maintain some of this hormone production. We hypothesize that associations between early menopause, lung health and mortality will vary based on type of menopause. Among 69,071 females from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, early menopause rates were 8.7%, 44.1%, and 72.8% in never smokers versus 12.1%, 51.6%, and 78.0% in ever smokers with natural, bilateral oophorectomy, or hysterectomy without bilateral oophorectomy, respectively. We analyzed the associations of early menopause and hormone therapy with lung health (physician diagnosed emphysema and chronic bronchitis and lung cancer incidence) and mortality (all-cause and cause-specific) outcomes by smoking status and menopause types. The most consistent associations were observed for all-cause mortality: 1) Except in never smokers who received hysterectomy only, early menopause was associated with higher all-cause mortality regardless of smoking status 2) hormone therapy was associated with lower all-cause mortality in all groups and the longer the use, the more beneficial the outcome; 3) the magnitude of this association was strongest in those who underwent bilateral oophorectomy. Furthermore, in ethnic disparity analysis, all-cause mortality was affected by early menopause to a lesser degree in non-Hispanic black ever smokers and there was increased benefit from hormone therapy in non-Hispanic black never smokers. Overall, we identified further evidence supporting early menopause as a risk factor for lung health and mortality and hormone therapy as being beneficial regardless of smoking status or menopause type. Our results support the “shorter lifetime estrogen exposure in early menopause” hypothesis and the clinical importance of hormone therapy beyond withdrawal symptom coping. Supported by National Cancer Institute (NCI) grant P30 CA118100. The authors thank the NCI for access to NCI's data collected by the PLCO Cancer Screening Trial (the Cancer Data Access System Project Number PLCO-981). Citation Format: Tessa Flores, Xiaochun Gai, Yiliang Zhu, Kimberly Leslie, Shuguang Leng. Associations of early menopause and hormone therapy with lung health and mortality among female never and ever smokers from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6465.

Serum Pepsinogen as a Biomarker for Gastric Cancer in the United States: A Nested Case-Control Study Using the PLCO Cancer Screening Trial Data.

Gastric cancer lacks specific symptoms, resulting in diagnosis at later stages and high mortality. Serum pepsinogen is a biomarker for atrophic gastritis, a gastric cancer precursor, and may be useful to detect persons at increased risk of gastric cancer. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was conducted in the United States between 1993 and 2001. ELISA-based pepsinogen tests were conducted on prediagnostic serum samples of 105 PLCO participants who developed gastric cancer and 209 age, sex, and race-matched controls. Pepsinogen positive (PG+) was defined as pepsinogen I ≤ 70 μg/L and pepsinogen I/II ratio ≤3.0. Results of conditional logistic regression models, and sensitivity and specificity, of PG+ for gastric cancer are reported. Gastric cancer cases were more likely to be PG+ (31.4% vs. 5.5%, P < 0.001) at baseline than controls. Compared to PG-, PG+ was associated with an 8.5-fold increased risk for gastric cancer [95% confidence interval (CI) = 3.8-19.4]. This risk remained significant after adjusting for Helicobacter pylori, family history of gastric cancer, education, smoking, and BMI (aOR, 10.6; 95% CI, 4.3-26.2). In subgroup analysis, PG+ individuals were 11-fold more like to develop non-cardia gastric cancer (OR, 11.1; 95% CI, 4.3-28.8); conversely, they were not significantly more likely to develop cardia gastric cancer (OR, 2.0; 95% CI = 0.3-14.2). PG+ status yielded low sensitivity but high specificity for both noncardia (44.3%; 93.6%) and cardia gastric cancer (5.7%; 97.2%). Prediagnostic serum pepsinogen levels from a large, prospective cohort study were associated with risk of gastric cancer, particularly noncardia gastric cancer. PG status may identify individuals at higher risk of noncardia gastric cancer for targeted screening or interventions. See related commentary by Zhou and Huang, p. 1257.

Other and All-Cause Mortality among Men Diagnosed with Prostate Cancer in the PLCO Trial

Men with prostate cancer have high cause-specific survival, and most deaths are from other causes. This study aimed to investigate other and all-cause mortality in a large cancer screening cohort. From the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial cohort, we selected men diagnosed with prostate cancer from 1994-2014. We examined other and all-cause survival by prostate cancer risk level, defined as the D'Amico categories for localized disease (low, intermediate and high risk) plus nonlocalized disease. We developed 3 Cox proportional hazards models to assess the relationship between risk level and survival. Model I controlled for age, race, study arm and diagnosis year. Model II additionally controlled for other demographic and medical history factors. Model III additionally controlled for initial treatment. Of 76,672 men in PLCO and 10,859 prostate cancer cases, 9,248 (85.2%) had known prostate cancer risk level (mean±SD age 70.4±6.2 years). Median followup time from diagnosis was 10.8 years (IQR 6.8-15.0). Of 3,318 deaths 81% were from other causes. Compared to the low risk group, other-cause mortality HRs were 1.13 (95% CI 1.04-1.23), 1.35 (95% CI 1.21-1.50) and 1.63 (95% CI 1.35-1.97) for intermediate risk, high risk and advanced disease, respectively, in model II. Model III HRs were similar to model II except for advanced disease, where the HR decreased to 1.35. Other-cause survival was greater in lower vs higher risk disease, even after controlling for lifestyle characteristics and comorbidities. Further research is needed to identify factors contributing to this higher other-cause mortality to help mitigate the risk.

Deep Learning Using Chest Radiographs to Identify High-Risk Smokers for Lung Cancer Screening Computed Tomography: Development and Validation of a Prediction Model.

Lung cancer screening with chest computed tomography (CT) reduces lung cancer death. Centers for Medicare & Medicaid Services (CMS) eligibility criteria for lung cancer screening with CT require detailed smoking information and miss many incident lung cancers. An automated deep-learning approach based on chest radiograph images may identify more smokers at high risk for lung cancer who could benefit from screening with CT. To develop and validate a convolutional neural network (CXR-LC) that predicts long-term incident lung cancer using data commonly available in the electronic medical record (EMR) (chest radiograph, age, sex, and whether currently smoking). Risk prediction study. U.S. lung cancer screening trials. The CXR-LC model was developed in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial (n = 41856). The final CXR-LC model was validated in additional PLCO smokers (n = 5615, 12-year follow-up) and NLST (National Lung Screening Trial) heavy smokers (n = 5493, 6-year follow-up). Results are reported for validation data sets only. Up to 12-year lung cancer incidence predicted by CXR-LC. The CXR-LC model had better discrimination (area under the receiver-operating characteristic curve [AUC]) for incident lung cancer than CMS eligibility (PLCO AUC, 0.755 vs. 0.634; P < 0.001). The CXR-LC model's performance was similar to that of PLCOM2012, a state-of-the-art risk score with 11 inputs, in both the PLCO data set (CXR-LC AUC of 0.755 vs. PLCOM2012 AUC of 0.751) and the NLST data set (0.659 vs. 0.650). When compared in equal-sized screening populations, CXR-LC was more sensitive than CMS eligibility in the PLCO data set (74.9% vs. 63.8%; P = 0.012) and missed 30.7% fewer incident lung cancers. On decision curve analysis, CXR-LC had higher net benefit than CMS eligibility and similar benefit to PLCOM2012. Validation in lung cancer screening trials and not a clinical setting. The CXR-LC model identified smokers at high risk for incident lung cancer, beyond CMS eligibility and using information commonly available in the EMR. None.

Relationship between prediagnostic body mass index trajectory and colorectal adenomas: an analysis of the PLCO cancer screening trial.

BackgroundStudies on the relationship between lifetime body mass index (BMI) trajectory and colorectal premalignant precursor lesions are limited. This study aimed to assess the relationship between prediagnostic adulthood BMI trajectory and the risk of colorectal adenomas using data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial.MethodsIn total, 39,824 participants in the intervention arm of the prospective PLCO cohort, who have undergone at least one colonoscopy or sigmoidoscopy examination with a confirmed diagnosis of colorectal adenomas, were enrolled and divided into four groups (underweight, normal weight, overweight, and obese) according to BMI during each age period. SAS Proc Traj was used to establish the BMI trajectory model. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsCompared with normal weight, overweight or obesity significantly increased colorectal adenomas risk in each age period after 30 years. Specifically, obesity in the 50s was most closely related to colorectal adenomas risk [HR: 1.32, 95% CI: (1.22, 1.43)]. BMI gain from the age of 40 to 50 [HR: 1.25, 95% CI: (1.11, 1.42)] showed the strongest correlation with an increased incidence of colorectal adenomas, followed by that from the age of 30 to 50 [HR: 1.19, 95% CI: (1.10, 1.29)], the age of 20 to 50 [HR: 1.16, 95% CI: (1.10, 1.24)], the age of 20 to 40 [HR: 1.14, 95% CI: (1.05, 1.23)], and the age of 20 to 30 [HR: 1.13, 95% CI: (1.02, 1.26)]. Additionally, compared with those who maintained normal weight throughout adulthood, those who progressed from normal weight to obesity [HR: 1.15, 95% CI: (1.06, 1.25)], or from overweight to obesity [HR: 1.33, 95% CI: (1.11, 1.61)], had a higher risk of colorectal adenomas.ConclusionsOverweight and obesity increased the risk of colorectal adenomas, and this risk increased with advancing age.

Association of Nonadherence to Cancer Screening Examinations With Mortality From Unrelated Causes

ImportancePatient nonadherence to chronic disease prevention guidelines is associated with increased mortality. Nonadherence to offered cancer screening tests may be associated with mortality among middle-aged and older adults.ObjectiveTo evaluate the association between nonadherence to cancer screening tests and mortality in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening trial, excluding mortality from cancers studied in the trial.Design, Setting, and ParticipantsRandomization at 10 US screening centers occurred from November 8, 1993, to July 2, 2001. Original follow-up was through 13 years or December 31, 2009. Participants were re-consented to further follow-up starting May 18, 2011, and were observed until December 31, 2012. Protocol screening tests for the PLCO Cancer Screening trial intervention arm participants (N = 77 443) included chest radiographs and flexible sigmoidoscopy for both sexes, prostate-specific antigen tests and digital rectal examinations for men, and cancer antigen 125 tests and transvaginal ultrasonography for women. At baseline, participants completed a self-administered questionnaire. The cohort was classified into those receiving all sex-specified PLCO Cancer Screening trial screening tests at baseline (fully adherent), those receiving some but not all baseline tests (partially adherent), and those receiving no baseline tests (nonadherents). Secondary analysis was ad hoc in the original trial protocol. Statistical analysis was conducted from November 24, 2017, to August 29, 2018.Main Outcomes and MeasuresMortality was ascertained via mailed annual study update questionnaires and searches of the National Death Index. Cox proportional hazards regression was used to analyze the association between mortality and adherence, controlling for various covariates.ResultsOf 77 443 participants in the intervention arm, 64 567 (29 537 women and 35 030 men; mean [SD] age, 62.3 [5.3] years) were included in the analysis based on consenting to trial participation before randomization and being eligible for all screening tests. Overall, 55 065 participants (85.3%) were adherent, 2548 (3.9%) were partially adherent, and 6954 (10.8%) were nonadherent with the baseline screening protocol. Within 10 years of follow-up, the hazard ratio of mortality, excluding deaths from cancers studied in the PLCO Cancer Screening trial and controlling only for age, sex, and race/ethnicity (model 1), was 1.73 (95% CI, 1.60-1.89) for nonadherent compared with fully adherent participants and 1.36 (95% CI, 1.19-1.54) for partially compared with fully adherent participants. After adjustment for medical risk factors for mortality and behavioral-related factors (model 2), the hazard ratio decreased to 1.46 (95% CI, 1.34-1.59) for nonadherent compared with fully adherent participants.Conclusions and RelevanceAmong participants in a screening trial for multiple cancers, a nonadherence behavior profile marked by nonadherence to protocol screenings was associated with higher overall mortality (excluding deaths from cancers studied in the trial). The generalizability of this finding to routine clinical practice should be assessed.Trial RegistrationClinicalTrials.gov identifier: NCT00002540

Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm

The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p <0.001). During followup there were 1,612 clinically significant prostate cancers detected, 64 prostate cancer specific deaths and 4,600 deaths. On multivariable analysis suspicious digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p<0.001 and p <0.001) and prostate cancer specific mortality (HR2.54, 95% CI1.41-4.58 vs HR 5.23, 95% CI 3.08-8.88, p=0.002 and p <0.001), respectively. In a secondary analysis of a contemporary U.S. cohort, suspicious digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed tooptimize screening protocols.

Building Successful Relationships in the PLCO Cancer Screening Trial.

Biomedical research cannot succeed without funding, knowledgeable staff, and appropriate infrastructure. There are however equally important but intangible factors that are rarely considered in planning large multidisciplinary endeavors or evaluating their success. The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial required extensive collaborations between individuals from many fields, including clinicians, clinical trialists, and administrators; it also addressed questions across the spectrum of cancer prevention and control. In this manuscript, we examine the experiences and opinions of trial staff regarding the building of successful relationships in PLCO. We summarize, in narrative form, data collected using open-ended questionnaires that were administered to the National Cancer Institute project officers, coordinating center staff, screening center principal investigators, and screening center coordinators in 2015, about 3 years after publication of the final primary trial manuscript. Trust, respect, listening to others, and in-person interaction were frequently mentioned as crucial to building successful relationships.

Data Processing and Analytic Support in the PLCO Cancer Screening Trial.

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial was a large, randomized controlled trial of cancer screening that also evolved over time into a unique epidemiologic cohort. Vast quantities of data have been collected since the beginning of the trial in 1993. Screening data was obtained through 2006. Questionnaire-based risk factor data (collected at baseline and at other points in the trial), vital status, cancer diagnoses and treatment, biospecimen data and additional ancillary efforts continue to be collected. Accurate data collection and efficient management methods are required to ensure high-quality data and valid and consistent analyses of trial outcomes. Information Management Services (IMS) was and continues to be responsible for processing and converting the collected raw PLCO data into comprehensive and accessible datasets. IMS also continues to provide a wide spectrum of analytic support including support for trial monitoring, data sharing, and epidemiologic research. In this paper, we describe the data processing and management requirements from the analytic team perspective, highlighting the various data sources and their complexity. We also illustrate the construction of usable analytic data files and discuss the wide range of analytic support provided. Instructions for accessing PLCO data also are provided.

Participants' Views of Retention Materials Used in the PLCO Cancer Screening Trial.

To obtain information from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial regarding their perception of the retention materials employed by the screening centers. Also, to determine the viability of using email or the internet as a data collection tool with an older population. Three of ten PLCO screening centers queried participants towards the end of the study (2010) as to their opinions of the various retention materials and whether they would have been willing to use electronic communication for study activities, had the option been available. The questionnaires were administered by mail, and responses were returned to the originating screening center. The participants in this study consisted of all the active participants at three PLCO screening centers: the University of Colorado Anschutz Medical Campus, the University of Utah, and Henry Ford Health System. A short, self-administered questionnaire was mailed to all active participants at three PLCO centers (n=41,482). This was a one-time mailing with no follow-up, as the responses were designed to be anonymous in order to obtain the most honest responses. The response rate was 62%. Of respondents, 97% reported their PLCO experience was good or excellent. Nearly 50% of respondents indicated that receipt of an annual newsletter made them more likely to participate; newsletter features they reported as most important were those that conveyed information on cancer, study findings, and how their data were being used. Results did not support study coordinators' suppositions that receipt of a token gift or birthday card by participants was important for retention. Fewer than 30% of respondents indicated that they would have been unwilling to use a secure website to complete study forms. These data indicate the importance of querying participants rather than relying on impressions of study staff, and also indicate that the internet will be a viable means of data collection in future prevention studies that include older Americans.

Abstract 4809: Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Abstract Background: Some published studies on dietary fat and risk of pancreatic cancer suggest that dietary fat and specific fat sources may increase risk of pancreatic cancer. Methods: We examined the association between fat intake (measured by food frequency questionnaire) and pancreatic cancer risk among 111,416 participants in the PLCO Cancer Screening Trial using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: There were 411 incident pancreatic cancer cases over the median 8.9 years of follow up. We observed an inverse association between saturated fat intake and pancreatic cancer risk comparing extreme quintiles (HR=0.64, 95% CI 0.46-0.88), but the association became weaker and non-significant when excluding individuals with &amp;lt;4 years of follow up to assess reverse causation HR=0.88 (95% CI 0.58-1.33). Total fat intake showed a similar pattern of association, while monounsaturated and polyunsaturated fat intakes and analysis by animal or plant source showed no association with risk. Conclusions: Despite more cases and longer follow up than most previous studies, our results do not suggest that higher fat consumption increases risk of pancreatic cancer. Lower fat intake in cases prior to diagnosis may reflect early manifestations of the disease (e.g. dyspepsia), and avoidance of fat which can exacerbate symptoms. Citation Format: Hannah E. Arem, Susan T. Mayne, Joshua Sampson, Harvey Risch, Rachael Z. Stolzenberg-Solomon. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4809. doi:10.1158/1538-7445.AM2013-4809

Abstract 3770: Long-term variation in serum 25-hydroxyvitamin D concentration among participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Molecular epidemiologic studies of vitamin D and risk of cancer and other health outcomes usually involve a single measurement of the biomarker 25-hydroxyvitamin D [25(OH)D] in serum or plasma. However, the extent to which 25(OH)D concentration at a single time point is representative of an individual's long-term vitamin D status is unclear. To address this question, we evaluated within-person variability in 25(OH)D concentration across serum samples collected at three time points over a five year period among 29 participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial blood samples in the PLCO Cancer Screening Trial were obtained from each subject at the same time of year for each of the three collection events. This sample collection protocol provided a unique opportunity to evaluate within-person temporal variability beyond seasonal effects, which have been well-characterized in previous studies. The within-person coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated using variance components estimated from random effects models. Spearman rank correlation coefficients were calculated to evaluate agreement between measurements at different collection times (baseline, +1 year, +5 years). The within-subject CV was 14.9% [95% confidence interval (CI) 12.4%-18.1%] and the ICC was 0.71 (95% CI 0.63-0.88). Spearman rank correlation coefficients comparing baseline to +1 year, +1 year to +5 years, baseline to +5 years, and the average of baseline and +1 year to +5 years were 0.65 (0.37-0.82), 0.61 (0.29-0.81), 0.53 (0.17-0.77), and 0.65 (0.34-0.83) respectively. After restricting to 23 non-Hispanic Caucasian subjects, the ICC was 0.75 (0.64-0.90) and slightly stronger pairwise correlations were observed: the correlation coefficients were 0.72 (0.42-0.87) for baseline vs. +1 year, 0.69 (0.37-0.87) for +1 year vs. +5 years, 0.58 (0.18-0.81) for baseline vs. +5 years, and 0.70 (0.37-0.87) for the average of baseline and +1 year vs. +5 years. These findings suggest that serum 25(OH)D concentration at a single time point may be a useful biomarker of long-term vitamin D status in population-based studies of various diseases. When possible, investigators might also consider taking multiple measurements from each subject at different times to reduce misclassification of vitamin D status, thereby improving the validity of risk estimates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3770.

Evidence of Pre-Diagnostic Monoclonality in Blood Obtained up to 6.4 Years Preceding Diagnosis of Chronic Lymphocytic Leukemia (CLL).

Background: Monoclonal B-cell lymphocytosis (MBL) is reported in about 3% of the general adult population 65 yrs or older. Risk of progression from MBL to CLL requiring treatment has been estimated to about 1% per yr. For the first time we established the occurrence of preceding MBL using prospectively collected pre-diagnostic samples from CLL pts. Also, we tested the hypothesis that indolent (IgVH mutated) CLL occurs after MBL while aggressive (IgVH unmutated) CLL has an alternative route that develops rapidly or bypasses MBL.Methods: Using the population-based nationwide PLCO (Prostate, Lung, Colorectal and Ovarian) cancer screening trial (n>144,500 cancer-free adults), we identified 46 CLL pts with available baseline cryopreserved whole blood obtained 3 to 77 months prior to CLL diagnosis. Clinical information was retrieved from screening questionnaires and medical records. 10 healthy adult controls were included. 6-color flow cytometry (CD45/CD19/CD5/CD10/kappa/lambda) and reverse transcription/polymerase chain reaction (RT/PCR) for IgH gene were used to determine evidence of expression of monoclonal IgH gene family and to establish the VH gene mutation status. Direct sequencing without subcloning (for clonal cases) and with subcloning (for non-clonal cases) was used to determine mutation status. We sequenced exons 5, 6, 7, 8, and 9 of the p53 suppressor gene for mutations.Results: After exclusion of one subject with absent viable cells, we analyzed pre-diagnostic blood specimen from 45 CLL pts. CLL diagnosis was based on clinical criteria and confirmed by review of clinical records. Immunophenotyping data were available for 39 (87%) pts. The Rai CLL stage distribution was: 0 (n=26), 1 (n=9), 2 (n=2), 3 (n=1), missing/unclear (n=7). The mean time between pre-diagnostic blood draw and subsequent CLL diagnoses was 3 yrs. Using flow cytometry, sequencing, and PCR, we demonstrated evidence of monoclonality in 43/45 (96%) pre-diagnostic samples from CLL pts. Among individuals whose blood was obtained <3 yrs vs. >3 yrs prior CLL diagnosis, the proportion of pre-diagnostic monoclonality was 28/28 (100%) vs. 15/17 (88%), respectively; the proportion of IgVH mutated pre-diagnostic clones was the same in both groups: 23/28 (82%) vs. 14/17 (82%). The most frequently expressed VH gene family was VH3 (40%) followed by VH4 (29%), VH1 (9%), VH5 (9%), VH2 (7%), and VH6 (2%), with no expression of VH7 gene families. We found 2 pts with mutations in the p53 suppressor gene; one in exon7/M237K, and one in exon 6, P22 that is silent and has been reported as in some tumors and a polymorphism. One sample with unmutated IgVH appeared to have a deletion at p53 in both alleles. Immunophenotyping analyses for pre-diagnostic clones showed kappa n=27, lambda n=8, n=4 biclonal, and missing/indeterminate n=6 (kappa:lambda ratio >3:1). Comparisons of pre-diagnostic and diagnostic kappa/lambda status in the same persons showed 100% concordance. All negative controls lacked evidence of monoclonality.Conclusions: In this first prospective study examining pre-diagnostic blood obtained 3 to 77 months prior to CLL diagnosis, we found a monoclonal B-cell population in virtually all the persons; 82% were IgVH mutated. Our findings suggest that CLL is commonly preceded by the precursor condition MBL.

Factors Affecting Older African American Women's Decisions to Join the PLCO Cancer Screening Trial

The purpose of this study is to describe the factors associated with the decisions of older African American women to join the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial when recruited. African American women between ages 55 and 74 years who were never diagnosed with a PLCO cancer were eligible for our study. Two methods of recruitment were used. First, mailings were sent to a random sample of women describing the PLCO followed by a telephone call to determine interest in the PLCO. If women were not interested in PLCO but consented to participate in our study, they were interviewed immediately. Second, we followed up with African American women who responded to mass mailings sent out before the start of our study by the Pittsburgh PLCO office. Women completed an interview about their cancer and clinical trial knowledge, attitudes, beliefs, and behaviors. The responses of women who joined the PLCO Trial are contrasted with the responses of women who did not join. Numerous factors were associated with the decision of older African American women to join the PLCO, including perceptions of cancer prevention and detection, the experience of having a loved one with cancer, knowledge of and experience with clinical trials, and beliefs regarding the benefits and risks of clinical trial participation. Minority recruitment to cancer clinical trials could be increased by designing interventions focused on individual, organizational, and community needs.

Flexible Sigmoidoscopy in the PLCO Cancer Screening Trial: Results From the Baseline Screening Examination of a Randomized Trial

The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial is a randomized clinical trial to test the effectiveness of cancer screening, including the effect of flexible sigmoidoscopy screening on colorectal cancer mortality. Here we report findings from the baseline screening flexible sigmoidoscopy examination. Analyses included 77,465 men and women aged 55-74 years who were enrolled at 10 screening centers. The trial administered baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy examinations, referred patients with screen-detected colorectal polyps or masses to personal physicians, and tracked subjects with polyps or masses to determine results from diagnostic follow-up. Cochran-Mantel-Haenszel statistics and logistic regression were used to test for differences in proportions according to sex and age. A total of 64 658 subjects (83.5%) underwent screening flexible sigmoidoscopy, and at least one polyp or mass was identified in 15,150 subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures. Follow-up lower endoscopy was more frequent in subjects with at least one larger (> or = 0.5 cm) polyp or mass (86.0% [95% confidence interval {CI} = 84.6% to 87.4%] and 81.0% [95% CI = 79.8% to 82.2%] in women and men, respectively) than in those with a smaller (< 0.5 cm) polyp or mass (69.1% [95% CI = 67.5% to 70.6%] and 65.4% [95% CI = 64.1% to 66.7%] in women and men, respectively). The yields per 1000 screened, depending on 5-year age group, were as follows: for colorectal cancer, 1.1-2.5 in women and 2.4-5.6 in men; for advanced adenoma, 18.0-30.4 in women and 36.1-49.1 in men; and for colorectal cancer or any adenoma, 50.6-79.6 in women and 101.9-128.6 in men. Approximately 77% (130/169) of the colorectal adenocarcinoma patients were stage I or II at diagnosis. Acceptance of screening flexible sigmoidoscopy was high. Diagnostic follow-up varied according to polyp size, yet cancer or adenoma detection rates met expectations.