The nutritional prevention of cancer: 400 mcg per day selenium treatment.

Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.

Pneumonectomy for bronchogenic carcinoma: analysis of factors predicting survival.

BACKGROUND: The aim of this study was to identify risk factors associated with survival after pneumonectomy for non-small cell lung cancer. METHODS: This was a retrospective study of 155 patients who underwent a pneumonectomy for non-small cell lung cancer at Roswell Park Cancer Institute between 1986 and 2002. Medical record review ascertained information on preoperative assessment including pulmonary function tests and clinical characteristics, postoperative complications, and overall survival. Multivariate Cox proportional hazards models to calculate the hazard ratios and 95% confidence intervals were used. Kaplan-Meier cumulative survival curves (with log-rank p values) were generated for selected variables. RESULTS: The median age was 58 years at the time of surgery; 65% of patients were males. Squamous cell carcinoma (54%) and adenocarcinoma (33%) were the predominant histologic types. The median time to relapse was 11 months, and the overall median survival was 15.6 months. An American Society of Anesthesiology score of less than 3, squamous histology, and lower pathologic stage were significant independent predictors of improved survival. Current smoking status (hazard ratio = 1.87, 95% confidence interval: 1.30 to 2.70) and left tumor location (hazard ratio = 1.40, 95% confidence interval: 0.97 to 2.03) were associated with a trend toward poorer survival. Sixty-four patients (41%) had postoperative complications. The operative mortality from pneumonectomy was 9 of 155 (5.8%). CONCLUSIONS: American Society of Anesthesiology score, histology, pathologic stage, smoking status, and location of the tumor were important predictors of survival in this patient sample. Pneumonectomy for non-small cell lung cancer carries an acceptable operative mortality and provides an important survival benefit.

Autofluorescence bronchoscopy for lung cancer surveillance based on risk assessment.

BACKGROUND: This is a preliminary report of an ongoing prospective bimodality lung cancer surveillance trial for high-risk patients. Bimodality surveillance incorporates autofluorescence bronchoscopy (AFB) and spiral CT (SCT) scanning in high-risk patients as a primary lung cancer surveillance strategy, based entirely on risk factors. AFB was used for surveillance and findings were compared with conventional sputum cytology for the detection of malignancy and pre-malignant central airway lesions. METHODS: 402 patients registering at Roswell Park Cancer Institute were evaluated with spirometric testing, chest radiography, history and physical examination, of which 207 were deemed eligible for the study. For eligibility, patients were required to have at least two of the following risk factors: (1) > or =20 pack year history of tobacco use, (2) asbestos-related lung disease on the chest radiograph, (3) chronic obstructive pulmonary disease with a forced expiratory volume in 1 s (FEV(1)) <70% of predicted, and (4) prior aerodigestive cancer treated with curative intent, with no evidence of disease for >2 years. All eligible patients underwent AFB, a low-dose SCT scan of the chest without contrast, and a sputum sample was collected for cytological examination. Bronchoscopic biopsy findings were correlated with sputum cytology results, SCT-detected pulmonary nodules and surveillance-detected cancers. To date, 186 have been enrolled with 169 completing the surveillance procedures. RESULTS: Thirteen lung cancers (7%) were detected in the 169 subjects who have completed all three surveillance studies to date. Pre-malignant changes were common and 66% of patients had squamous metaplasia or worse. Conventional sputum cytology missed 100% of the dysplasias and 68% of the metaplasias detected by AFB, and failed to detect any cases of carcinoma or carcinoma-in-situ in this patient cohort. Sputum cytology exhibited 33% sensitivity and 64% specificity for the presence of metaplasia. Seven of 13 lung cancers (58%) were stage Ia or less, including three patients with squamous cell carcinoma. Patients with peripheral pulmonary nodules identified by SCT scanning of the chest were 3.16 times more likely to exhibit pre-malignant changes on AFB (p<0.001). CONCLUSION: Bimodality surveillance will detect central lung cancer and pre-malignancy in patients with multiple lung cancer risk factors, even when conventional sputum cytology is negative. AFB should be considered in high-risk patients, regardless of sputum cytology findings.

Genomic profiles of colorectal cancers differ based on patient smoking status.

Human sporadic colorectal cancer is the result of a lengthy somatic evolutionary process facilitated by various forms of genomic instability. Such instability arises endogenously from mutations in genes whose role is to preserve genomic integrity, and exogenously from environmental agents that generate genomic damage. We have found that cigarette smoking shifts the genomic profiles and genomic instability patterns of colorectal carcinomas. The genomic profiles of 57 consecutive cancers were examined; 31 cases were current or former smokers and 26 were nonsmokers. Genome-wide allelotypes of 348 markers were examined, along with comparative genomic hybridization (CGH) on ordered BAC microarrays, microsatellite instability, and inter-(simple sequence repeat) polymerase chain reaction instability. Tumors from nonsmokers exhibited losses of heterozygosity, particularly on chromosomes 14 and 18, whereas tumors from smokers exhibited a more diffuse pattern of allelic losses. Tumors from smokers exhibited higher overall rates of loss of heterozygosity, but showed lower rates of background microsatellite instability (MSI-L). On BAC array CGH, higher levels of generalized amplifications and deletions were observed in tumors from smokers, differentially affecting male smokers. In the transforming growth factor-beta signaling pathway, MADH4 mutations were more common in tumors from smokers, whereas transforming growth factor-beta RII mutations were more common among nonsmokers.

Regular aspirin use and esophageal cancer risk.

Given the high mortality rate and the rapidly increasing incidence rate of esophageal carcinoma, chemopreventive agents are highly desirable. Aspirin has been shown to be associated with reduced risk of developing colorectal carcinoma and other cancers. Even though previous studies have shown reduced risk of esophageal cancer associated with aspirin use, results were inconsistent with respect to frequency and duration of use. In this hospital-based case-control study, 163 esophageal cancer cases were compared to 482 age- and sex-matched hospital controls with nonneoplastic conditions. Participants were classified as regular aspirin users if they had taken the drug at least once a week for 6 months. Results suggest that esophageal cancer risk is significantly lower for regular aspirin users compared to nonusers [adjusted odds ratio (aOR) 0.54; 95% confidence interval (CI) 0.36-0.86]. Individuals who used an equivalent of at least 1 aspirin a day (> or =7 tablets/week) were half as likely to have been diagnosed with esophageal carcinoma (aOR 0.47; 95% CI 0.26-0.85), and a linear trend was noted with increasing frequency of use (p(trend) 0.007). Similar protective effects were noted with < or =20 years of use, whereas no risk reduction was noted with >20 years of use. Consistent reduction in risk associated with aspirin use was noted among both the major histological subtypes, but the protective effect appears to be more pronounced in adenocarcinoma compared to squamous cell carcinoma. Overall, results from the current study suggest that regular aspirin use may be associated with reduced risk of esophageal cancer.

Ovarian cancer incidence in the United States, 1992-1999.

OBJECTIVE: The purpose of this epidemiological study was to report histology-specific age-adjusted ovarian cancer incidence rates that were standardized to the recently adopted year 2000 United States standard population. METHODS: We utilized data gathered from eleven population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute for the years 1992 through 1999. Our analyses included data on 23,484 microscopically confirmed cases of primary malignant ovarian cancer that were diagnosed in women residing in the eleven SEER registries. RESULTS: We categorized the 117 different histologies that were diagnosed in the 23,484 ovarian cancer cases into ten major classifications. The overall age-adjusted incidence rate for all ovarian cancer cases was 16.23 cases per 100,000 women. Epithelial tumors displayed the highest age-adjusted incidence rate (15.48), followed by germ cell tumors (0.41), sex cord-stromal tumors (0.20), and all other miscellaneous ovarian tumors (0.13). Serous epithelial tumors were the most commonly observed epithelial group (6.77 cases per 100,000 women), followed by other miscellaneous epithelial tumors (3.76), mucinous epithelial tumors (2.22), endometrioid epithelial tumors (2.11), and clear cell epithelial tumors (0.64). Notable differences were observed in the age-adjusted incidence rates for White and Black women. CONCLUSIONS: Age-adjusted incidence rates of ovarian cancer vary by histology. This is the first study to standardize histology-specific age-adjusted incidence rates of ovarian cancer to the new 2000 United States standard population.

Immunogenicity in humans of an edible vaccine for hepatitis B.

A double-blind placebo-controlled clinical trial evaluated the immunogenicity of hepatitis B surface antigen (HBsAg) expressed in potatoes and delivered orally to previously vaccinated individuals. The potatoes accumulated HBsAg at approximately 8.5 microg/g of potato tuber, and doses of 100 g of tuber were administered by ingestion. The correlate of protection for hepatitis B virus, a nonenteric pathogen, is blood serum antibody titers against HBsAg. After volunteers ate uncooked potatoes, serum anti-HBsAg titers increased in 10 of 16 volunteers (62.5%) who ate three doses of potatoes; in 9 of 17 volunteers (52.9%) who ate two doses of transgenic potatoes; and in none of the volunteers who ate nontransgenic potatoes. These results were achieved without the coadministration of a mucosal adjuvant or the need for buffering stomach pH. We conclude that a plant-derived orally delivered vaccine for prevention of hepatitis B virus should be considered as a viable component of a global immunization program.

Cigarette smoking and the risk of bladder cancer in men and women.

Although cigarette smoking is a principal risk factor for bladder cancer in both men and women, few studies have statistically evaluated whether gender modifies the effect of smoking on bladder cancer risk. We initiated the present case-control study at Roswell Park Cancer Institute in Buffalo, New York, U.S., to provide further data on this important issue. We observed similar risk estimates for men and women with comparable smoking exposures, but did not observe a statistically significant interaction between gender and lifetime smoking exposure. We conclude that cigarette smoking is a major risk factor for bladder cancer in both sexes, but that gender does not modify the effect of smoking on bladder cancer risk.

Nested case-control study of external ionizing radiation dose and mortality from dementia within a pooled cohort of female nuclear weapons workers.

BACKGROUND: A prior investigation of this cohort of female nuclear workers found increased deaths from mental disorders, including dementia. The present study estimates the effect of workplace exposures to ionizing radiations and other hazards on mortality from dementia. METHODS: A nested case-control study within a pooled cohort of 67,976 female nuclear workers compared 91 cases of death from dementia with 910 controls. Adjusted odds ratios (ORs) were employed to estimate the effects of maximum annual and total lifetime radiation doses on the occurrence of dementia in 168 monitored workers. RESULTS: Both maximum annual (OR = 2.11, 95% confidence interval (CI) = 0.98, 4.40) and total lifetime radiation doses (OR = 2.09, 95% CI = 1.02, 4.29) were associated with death from dementia. Significant dose-response trends were present for both exposures. CONCLUSIONS: Occupational exposure to ionizing radiation (IR) may be associated with increased risk of death from dementia in female workers. Since these findings are based on a small number of cases, replication with a larger case sample should be pursued.