Associations between hepatocyte growth factor, c-Met, and basic fibroblast growth factor and survival in endometrial cancer patients.

BACKGROUND: Hepatocyte growth factor (HGF), c-Met, and basic fibroblast growth factor (bFGF) are molecular markers that contribute to angiogenesis and proliferation in numerous cancers. We assessed the prognostic significance of these factors in tumour and stroma of endometrial cancer (EC) patients (n=211). METHODS: Immunohistochemistry (IHC) was used to detect tumour and stromal protein expression of the biomarkers. Associations between expression and clinicopathological factors were assessed using Chi-square tests. Kaplan-Meier curves, log-rank tests, and Cox regression were used to summarise associations between biomarker expression and overall survival (OS) and recurrence-free survival (RFS). RESULTS: Tumour bFGF was significantly associated with high-grade endometrioid and clear cell histology (P<0.001), advanced stage (P=0.008), positive lymph-node involvement (P=0.002), poor OS (log-rank test, P=0.009), and poor RFS (P<0.001). In multivariable analyses, cases with HGF-positive, stromal bFGF-positive tumours had a lower risk of death compared with cases with HGF-positive, stromal bFGF-negative tumours (hazard ratio (HR): 0.14, 95% CI: 0.03, 0.60). Cases with HGF-positive, bFGF-positive tumours had a higher risk of recurrence compared with cases with negative expression of both markers (HR: 9.88, 95% CI: 2.63, 37.16). CONCLUSION: These IHC data show that tumour and stromal bFGF expression have opposite associations with survival outcomes in EC patients. If confirmed in larger studies, tumour-derived bFGF could be an attractive target in EC therapy.

11q13 amplification status and human papillomavirus in relation to p16 expression defines two distinct etiologies of head and neck tumours.

Two distinct etiologies of head and neck squamous cell carcinoma (HNSCC) have been proposed, DNA damage owing to tobacco and alcohol exposure and human papillomavirus (HPV) oncogene-mediated transformation. Common genetic alterations in HNSCC include TP53 mutations, 11q13 amplification (amp) and CDKN2A/p16 mutations or promoter methlyation. However, in HPV+ HNSCC it is frequent to observe wild-type TP53 and expression of p16. The relationship of this unusual pattern with 11q13 amp has not been tested. In a retrospective study on 125 HNSCC patients, only 17% (five out of 30) of HPV+ vs 44% (39 out of 89) of HPV - tumours expressed 11q13 amp (adjusted odds ratio (OR)=0.2, 95% confidence interval (CI)=0.1-0.6). A subpopulation of tumours (n=69) were classified according to the three molecular markers, TP53, p16 and 11q13 amp. In addition to wild-type TP53, and p16 expression, HPV+ tumours were more likely not to be amplified at 11q13 (OR=6.5, 95% CI=1.8-23.9). As HPV+ HNSCC lack the genetic alterations which are common in other tumours, we hypothesise that HPV infection may represent an early event in the HNSCC carcinogenic process, thus suggesting a distinct molecular pathway.

Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth. METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants. RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk. CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

Allelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer risk.

PURPOSE: The purpose of this study was to determine whether polymorphisms in the CAG repeat in exon 1 of the androgen receptor (AR), two intronic restriction sites in the estrogen receptor (ESR1 XbaI and ESR1 PvuII), and an Arg264Cy5 substitution in the aromatase gene (CYP19) contribute to prostate cancer risk. EXPERIMENTAL DESIGN: A case-control study was performed with 88 Caucasian prostate cancer patients and 241 Caucasian male controls. Logistic regression models were used to assess individual and joint contributions of genotypes to prostate cancer risk. RESULTS: For single polymorphisms, only the AR repeat number was significantly related to increased prostate cancer risk [age- and body mass index (BMI)-adjusted odds ratio (OR), 1.14; 95% confidence interval (CI), 1.04-1.25], suggesting a 14% increase in risk for each missing CAG repeat. When subjects were classified as either long (> or =23 AR CAG repeats) or short (<23 repeats) carriers, a significant increase in risk was also observed (age- and BMI-adjusted OR, 1.75; 95% CI, 1.05-2.95; P = 0.04). The aromatase C/T was associated with an increase in risk of borderline significance (age- and BMI-adjusted OR, 2.50; 95% CI, 0.99-6.28). When examining the effects of two polymorphisms on prostate cancer risk, homozygosity for the ESR1 XbaI restriction site together with a longer AR was more frequent among controls (32%) than cases (18%; age- and BMI-adjusted OR, 0.39; 95% CI, 0.19-0.78). The aromatase C/C genotype together with a longer AR was also more frequent among controls (55%) than cases (41%; age- and BMI-adjusted OR, 0.51; 95% CI, 0.30-0.89). CONCLUSIONS: Estrogen and aromatase may play a role in prostate cancer. A multigenic model of prostate cancer susceptibility is also supported.

Is shorter always better? Relative importance of questionnaire length and cognitive ease on response rates and data quality for two dietary questionnaires.

In this study, the authors sought to determine the effects of length and clarity on response rates and data quality for two food frequency questionnaires (FFQs): the newly developed 36-page Diet History Questionnaire (DHQ), designed to be cognitively easier for respondents, and a 16-page FFQ developed earlier for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The PLCO Trial is a 23-year randomized controlled clinical trial begun in 1992. The sample for this substudy, which was conducted from January to April of 1998, consisted of 900 control and 450 screened PLCO participants aged 55-74 years. Controls received either the DHQ or the PLCO FFQ by mail. Screenees, who had previously completed the PLCO FFQ at baseline, were administered the DHQ. Among controls, the response rate for both FFQs was 82%. Average amounts of time needed by controls to complete the DHQ and the PLCO FFQ were 68 minutes and 39 minutes, respectively. Percentages of missing or uninterpretable responses were similar between instruments for questions on frequency of intake but were approximately 3 and 9 percentage points lower (p < or = 0.001) in the DHQ for questions on portion size and use of vitamin/mineral supplements, respectively. Among screenees, response rates for the DHQ and the PLCO FFQ were 84% and 89%, respectively, and analyses of questions on portion size and supplement use showed few differences. These data indicated that the shorter FFQ was not better from the perspective of response rate and data quality, and that clarity and ease of administration may compensate for questionnaire length.

Patient satisfaction with screening flexible sigmoidoscopy.

BACKGROUND: Screening flexible sigmoidoscopy is an underused cancer prevention procedure. Physicians often cite patient discomfort as a reason for not requesting sigmoidoscopy, but patient experiences and attitudes toward sigmoidoscopy have not been well studied. OBJECTIVE: To measure patient satisfaction and the determinants of satisfaction with screening sigmoidoscopy. METHODS: An instrument to assess satisfaction with screening sigmoidoscopy was developed. Responses were evaluated with a factor analysis, tested for reproducibility and internal consistency, and validated against an external standard. RESULTS: A total of 1221 patients (666 men and 555 women; mean age, 61.8 years) were surveyed after sigmoidoscopy. Examinations were performed by a nurse practitioner (n = 668), internist (n = 344), or gastrointestinal specialist (n= 184). More than 93% of the participants strongly agreed or agreed they would be willing to undergo another examination, and 74.9% would strongly recommend the procedure to their friends. Regarding pain and discomfort, 76.2% strongly agreed or agreed that the examination did not cause a lot of pain, 78.1% stated that it did not cause a lot of discomfort, and 68.5% thought that it was more comfortable than they expected. Fifteen percent to 25% of the patients indicated they had a lot of pain, great discomfort, or more discomfort than expected. Women were more likely to have significant pain or discomfort than men (adjusted odds ratio, 2.9; 95% confidence interval, 1.9-4.3; P<.001). CONCLUSIONS: Approximately 70% of individuals who undergo screening sigmoidoscopy are satisfied and find the procedure more comfortable than expected, whereas only 15% to 25% find the procedure unpleasant. Physicians should not project discomfort onto patients as a reason for not requesting screening sigmoidoscopy.

Reproducibility in the assessment of postmenopausal ovaries with transvaginal ultrasound.

OBJECTIVE: The goal of this study was to evaluate the interexaminer variation in the assessment of postmenopausal ovaries using transvaginal ultrasound (TVU). METHODS: One hundred eighty-eight cancer screening trial participants undergoing TVU were reassessed by a second TVU examination. RESULTS: Although first examiners tended to describe significantly larger left (P < 0.001) but smaller right (P = 0.036) ovaries, as well as fewer ovarian abnormalities, examiners agreed on the test interpretation 93% of the time (kappa = 0.846). In only two cases (1%) were the differences in interpretation such that the two examiners recommended different follow-up procedures. CONCLUSIONS: Because of the high fatality rate of ovarian cancer, early detection remains the best way to combat this devastating disease. TVU is one screening technique we are currently evaluating in a cancer screening trial. To help ensure screening test reproducibility, we have followed explcit protocols for training and certifying all TVU examiners, as well as for conducting TVU examinations. This study demonstrates that by adhering to specific training, certification, and examination protocols, TVU reproducibility is excellent. Such protocols may well serve as a standard for TVU training and examination.

Design of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The objectives of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55-74 at entry whether screening with flexible sigmoidoscopy (60-cm sigmoidoscope) can reduce mortality from colorectal cancer, whether screening with chest X-ray can reduce mortality from lung cancer, whether screening men with digital rectal examination (DRE) plus serum prostate-specific antigen (PSA) can reduce mortality from prostate cancer, and whether screening women with CA125 and transvaginal ultrasound (TVU) can reduce mortality from ovarian cancer. Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity, specificity, and positive predictive value; to assess incidence, stage, and survival of cancer cases; and to investigate biologic and/or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints. The design is a multicenter, two-armed, randomized trial with 37,000 females and 37,000 males in each of the two arms. In the intervention arm, the PSA and CA125 tests are performed at entry, then annually for 5 years. The DRE, TVU, and chest X-ray exams are performed at entry and then annually for 3 years. Sigmoidoscopy is performed at entry and then at the 5-year point. Participants in the control arm follow their usual medical care practices. Participants will be followed for at least 13 years from randomization to ascertain all cancers of the prostate, lung, colorectum, and ovary, as well as deaths from all causes. A pilot phase was undertaken to assess the randomization, screening, and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels. This paper describes eligibility, consent, and other design features of the trial, randomization and screening procedures, and an outline of the follow-up procedures. Sample-size calculations are reported, and a data analysis plan is presented.

Etiologic and early marker studies in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which is randomizing 74,000 screening arm participants (37,000 men, 37,000 women; ages 55-74) and an equal number of nonscreened controls, is a unique setting for the investigation of the etiology of cancer and other diseases and for the evaluation of potential molecular markers of early disease. At entry, baseline information is collected by questionnaire on dietary intake, tobacco and alcohol use, reproductive history (for women), family history of cancer, use of selected drugs, and other selected risk factors. Blood samples collected at the baseline screening exam are aliquoted to serum, plasma, red blood cell, and buffy coat fractions. At the next two annual screening visits, serum samples are collected. At the third annual reexamination, cryopreserved whole blood is obtained, in addition to serum, plasma, red blood cell, and buffy coat fractions. At the fourth and fifth years, serum, plasma, and buffy coat are collected. All blood samples are shipped to a central repository for long-term storage at -70 degrees C. Dietary questionnaires and buccal cells for DNA analysis are obtained from nonscreened controls. Cancer cases are identified through annual follow-up questionnaires, and all deaths are identified through vital status tracing mechanisms. Procedures are being developed to obtain archival pathologic material for selected cases of cancer and related diseases. Initial investigations are focusing on the etiology of colorectal cancer and on the operative characteristics of tests for the early detection of colorectal and prostate cancer.

Quality control of cancer screening examination procedures in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Investigators for the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial describe quality control procedures for the digital rectal examination, ovarian palpation examination, transvaginal ultrasound, chest X-ray, and flexible sigmoidoscopy. These cancer screening tests are subjective and difficult to standardize. PLCO quality control procedures aim to measure and, where possible, reduce variation, across examiner and screening center, with respect to cancer screening test performance. Initial protocols stressed examiner qualifications, experience, and training; equipment specifications; examination procedures; and definitions for positive tests. The PLCO quality assurance subcommittee developed a final quality assurance plan, which included central approval and registration of PLCO examiners, direct observation of screening test performance during periodic site visits by the National Cancer Institute and coordinating center auditors, periodic analysis of screening test data, and procedures for independently duplicating or reviewing selected examinations. For each modality, the periodic data analyses examine the test-positive and the test-inadequate proportions and aim to identify divergent centers or examiners. Procedures for duplicating examinations specify feasible sample sizes for precise estimates of agreement between examiners, at each center, for each screening test modality, and over a 1-year period. These quality control procedures will help characterize the consistency and reliability of the PLCO cancer screening tests.

Death review process in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The procedures that have been adopted in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial are described. These procedures have been designed to ensure unbiased decisions on the underlying cause of death for all confirmed or suspected PLCO cancers. A death review committee with a nonvoting chair and three experienced reviewers as members has been appointed. After an initial pilot study, the procedures have been instituted and are working well.

Screening mammography and late-stage breast cancer: a population-based study.

BACKGROUND: Among 50- to 69-year-old women, randomized clinical trials show breast cancer mortality reductions from screening mammography. However, few studies examine the long-term health effects and outcomes from screening mammography in community practice. The purpose of this study was to evaluate one approach for determining the effectiveness of screening mammography, as it is practiced in community settings, and to measure the prevalence of prior screening mammography among women with incident breast cancer. METHODS: This study was a population-based survey of the general community. Participants were 406 women with breast cancer diagnosed in 1993. The main outcome measure was breast cancer, late stage at diagnosis or fatal within 2 to 3 years of diagnosis. RESULTS: Sixty-four (57.7%) of 111 women with late-stage and 123 (42.1%) of 292 women with early-stage breast cancer did not have a screening mammogram in the 4 calendar years (1989-1992) before diagnosis. Relative to women with early-stage breast cancer, mammography nonuse in 1989-1992 was significantly more frequent among women with late-stage breast cancer (age-adjusted odds ratio 2.3, 95% confidence interval 1.3-4.3). Prior mammography was particularly infrequent among 42 women with breast cancer incident in 1993 and fatal before January 1996. CONCLUSIONS: Prior mammography among women with late-stage or fatal breast cancer was relatively infrequent. Late-stage or fatal breast cancer lacking prior mammography constitutes a missed public health opportunity. Also, this population-based study showed the expected association between prior mammography and late-stage or fatal breast cancer. These results are consistent with the effective practice of mammography in a community setting. The results illustrate and validate a public health approach that uses prior mammography histories among women with incident breast cancer to evaluate mammography penetration and quality in defined communities.

Is colonoscopy needed for the nonadvanced adenoma found on sigmoidoscopy? The Polyp Prevention Trial.

BACKGROUND & AIMS: The need for colonoscopy when small tubular adenomas with low-grade dysplasia are found on sigmoidoscopy is uncertain. The aim of this study was to examine the prevalence and characteristics of proximal adenomas in patients with distal adenomas. METHODS: We studied 981 subjects with distal adenomas found on the index colonoscopy before randomization in the Polyp Prevention Trial. RESULTS: Four hundred sixty patients (46.9%) had >/=1 distal adenoma that was pathologically advanced (villous component, high-grade dysplasia, or >/=1 cm); 21.5% (211 of 981) had any proximal adenoma; and 4.3% (42 of 981) (95% confidence interval [CI], 3.0-5.5) had an advanced proximal adenoma. A greater percentage of patients with an advanced distal adenoma (5.9%) (95% CI, 3.7-8.0) had an advanced proximal adenoma compared with those with a nonadvanced distal adenoma (2.9%) (95% CI, 1.4-4.3) (OR, 2.1; 95% CI, 1.1-4.3; P = 0.03). Not performing a colonoscopy in patients with a nonadvanced distal adenoma would have missed 36% (15 of 42) of the advanced proximal adenomas. CONCLUSIONS: Patients with an advanced distal adenoma are twice as likely to have an advanced proximal adenoma as patients with a nonadvanced distal adenoma. However, eschewing a colonoscopy in patients with a nonadvanced distal adenoma would result in not detecting a sizeable percentage of the prevalent advanced proximal adenomas. These data support performance of a colonoscopy in patients with a nonadvanced distal adenoma. Confirmation of these results in asymptomatic subjects undergoing screening sigmoidoscopy is advisable.

Bone mineral density and risk of breast cancer: differences by family history of breast cancer. Study of Osteoporotic Fractures Research Group.

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

Sagittal diameter in comparison with single slice CT as a predictor of total visceral adipose tissue volume.

BACKGROUND: Abdominal obesity has an important biological and epidemiological relationship to disease. The gold standard for measurement of visceral adipose tissue (VAT) is assessment by computerized tomography (CT) or magnetic resonance imaging (MRI), but because of simplicity and ease in collection, anthropometric variables are a desirable alternative to estimate VAT. OBJECTIVE: To compare the abilities of a single slice CT scan through the L4-L5 interspace (L4-L5 VAT), sagittal diameter, and body mass index (BMI) to estimate total volume VAT. Total volume VAT (the gold standard) was measured by total abdominal CT scanning, with a mean of 42 CT slices per patient. Estimation of VAT in subjects of similar body size was emphasized. DESIGN: Retrospective study of subjects undergoing complete abdominal and pelvic CT scanning for clinical reasons. SUBJECTS: 40 subjects (20 men and 20 women) mean age 56.5y, with a balanced selection for BMI < 27 and > 27. RESULTS: In univariate regression models, L4-L5 VAT explained the largest proportion of the variance in total VAT (R2=0.87 [P<0.001]), though age (R2=0.11 [P=0.04]), BMI (R2=0.37 [P<0.001]), and sagittal diameter (R2=0.50 [P < 0.001]) were also statistically significantly related to total VAT. When limited to individuals with a BMI > or= 27 however, L4-L5 VAT explained a large proportion of the variance in total VAT (R2=0.87 [P < 0.001]) whereas sagittal diameter was only of borderline significance (R2=0.20 [P=0.06]), and BMI was not associated with total VAT (R2=0.04 [P=NS]). In multiple regression analyses, L4-L5 VAT area explained a large proportion of the variance (0.84-0.90), and once in the model, BMI, sagittal diameter, and age did not additionally contribute significantly to the explained variance in total VAT. CONCLUSIONS: Abdominal sagittal diameter is poorly correlated to total VAT for men and women with a BMI > 27. Within a 2 cm range of sagittal diameter, there is nearly a three-fold variability in total VAT.

Use of calcium channel blockers and breast carcinoma risk in postmenopausal women.

BACKGROUND: The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age > or = 65 years. METHODS: Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers. RESULTS: In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08). CONCLUSIONS: Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers.

Etiology of Barrett's metaplasia and esophageal adenocarcinoma.

The incidence of esophageal adenocarcinoma in the United States is rising at an epidemic rate. Although the cause for this rapid rise is unclear, it is well established that nearly all cases of esophageal adenocarcinoma arise from a premalignant lesion of the esophagus, known as Barrett's esophagus. Although Barrett's esophagus is recognized as a precursor lesion, the etiology, prevalence, and malignant risk of this lesion remain unclear. The relatively short, two-decade time frame for the rise in esophageal adenocarcinoma incidence and the increase across populations is a strong argument for environmental factors as etiological agents, perhaps interacting with genetically determined characteristics that define personal susceptibility. Because of the strong link between Barrett's esophagus and esophageal adenocarcinoma and the link between Barrett's esophagus and gastroesophageal reflux disease, risk factors for gastroesophageal reflux disease have been the prime suspects offered as possible explanations for the rise in esophageal adenocarcinoma. A plethora of hypotheses have been advanced, implicating tobacco and alcohol consumption, changes in obesity and diet, and the changing pattern in use of medications that affect the upper gastrointestinal tract. The following text will review what is currently known about the epidemiology of Barrett's metaplasia, its risk for malignant transformation, and the proposed theories of etiogenesis.

Model of the impact of HIV infection on the size of future hemophilia and carrier birth cohorts.

The introduction of human immunodeficiency virus (HIV) infection in almost half of the U.S. hemophilia population during the late 1970s and early to mid-1980s has resulted in significant mortality and morbidity. The predict the quantitative impact of HIV infection through HIV-contaminated clotting factor on the size of future hemophilia and hemophilia carrier populations in the United States, a demographic model was developed for hemophilia and hemophilia carrier birth cohorts for the 200 years between 1980 and 2180. Mortality and fertility rates were estimated from databases of the Hemophilia Malignancy Study (HMS), NHLBI Blood Resources Studies, and Centers for Disease Control (CDC) Minimal Data Set. According to the model, the HIV epidemic will produce small reductions in the expected numbers of hemophilic (1.79%) and carrier (2.63%) births in the next 2 centuries. More substantial reductions in the numbers of hemophilic and carrier births required extreme assumptions regarding the fertility of hemophilic men, the extent of HIV infection among hemophilic men, and the proportion of hemophilic births that arise from spontaneous mutation.

Oncogene-related serum proteins and cancer risk: a nested case-control study.

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