Time course of the renal functional response to partial nephrectomy: measurements in conscious rats.

Previous investigations into the functional responses of the surviving nephrons following reductions in renal mass have been performed largely in anaesthetized animals and have taken little account of how the compensatory changes develop with time. The present study has assessed a method for determining glomerular filtration rate (GFR) in unrestrained, uncatheterized, conscious rats (plasma disappearance of (99m)Tc-diethylenetriamene pentaacetic acid (DTPA)) and has used this method to document the time course of the changes in GFR over a 32 day period following uninephrectomy or 5/6 nephrectomy. Concurrent measurements of excretion rates and of the clearance of lithium (the latter being an index of end-proximal fluid delivery) provided information on changes in overall tubular function and segmental reabsorption. After uninephrectomy, the GFR of the remaining kidney (compared with that of a single kidney of sham-operated animals) increased maximally (by approximately 50%) within 8 days; after 5/6 nephrectomy, the increase in the GFR of the remnant kidney was maximal (at approximately 300%) within 16 days. Overall excretion rates of sodium and potassium were well maintained in partially nephrectomized animals throughout the period of study, while the excretion of water increased (by approximately 30% after uninephrectomy and by approximately 120% after 5/6 nephrectomy), partly as a result of the compensatory increases in GFR but mainly as a consequence of moderate (after uninephrectomy) or marked (after 5/6 nephrectomy) reductions in fractional reabsorption. During the early period after 5/6 nephrectomy, potassium excretion sometimes exceeded the filtered load, indicating net secretion. Lithium clearance data indicated that the changes in tubular function after 5/6 nephrectomy include a reduction in fractional reabsorption in the proximal tubule, whereas after uninephrectomy any such effect on the proximal tubule is minor and transient.

Allostatic load and health disparities: a theoretical orientation.

Eliminating racial and ethnic health disparities requires restructuring the biomedical models that have focused on the individual as the level of analysis and emphasized the parts rather than the whole. A recently developed understanding of human physiology and adaptive regulation, constructs of allostasis and allostatic load, provides a theoretical orientation that needs to be explored. Thus, the purpose of this article is to present an orientation of allostasis and allostatic load as a theoretical framework for exploring health disparities. This article will (a) present a general background on the evolution of relevant physiologic theories, (b) offer the general theoretical definitions and explanations of allostasis, allostatic load, and mediation processes, (c) examine empirical evidence for the constructs, and (d) discuss the implications of this orientation for health disparities research.

A qualitative study of head and neck cancer.

The findings presented contribute to quality of life (QOL) research by highlighting the significance of factors affecting the communication by patients with primary-stage squamous cell carcinoma of the head and neck cancer (SCCHN) of their experiences of suffering after treatment to their clinicians. Qualitative research methodology based on open-ended interviews with 18 survivors of American Joint Committee on Cancer primary stage I and II SCCHN were used. The interviews were transcribed verbatim and thematically analyzed. Three important themes emerged: (1). a diminished self (2). fears of addiction, and (3). hopelessness and the loss of meaning in life after SCCHN. The findings indicate that SCCHN patients under-report their experiences mainly due to fear. As a consequence, and perhaps due to a failure on the part of clinicians and patients to adequately address such fears, SCCHN patients may experience greater psychological morbidity, becoming increasingly fatalistic about biomedicine's ability to restore them to health after cancer despite being "cured", or to relieve related symptoms. This qualitative study provides a perspective as to why such under-reporting occurs, thereby potentially enhancing clinician-patient communication and the QOL of SCCHN patients who present with curable disease.

Communicating suffering in primary stage head and neck cancer.

The findings presented in this discussion seek to make a contribution to quality of life (QOL) research, by highlighting the import of factors affecting the communication of primary stage head and neck cancer patient's experiences of suffering after treatments by their clinicians. Qualitative research methodology based on open-ended interviews with 18 survivors of American Joint Committee on Cancer (AJCC) Stage I and Stage II, squamous cell carcinoma of the head and neck (SCCHN) were used. The interviews were transcribed verbatim and thematically analysed. In this preliminary analysis, three important themes emerged: (1) a self diminished by cancer; (2) the fear of addiction to pain medications; and (3) hopelessness and the loss of meaning in life after SCCHN. Our present findings indicate that SCCHN patients understand their experiences of cancer and under-report their experiences of suffering mainly because of fear. These include fears of: being further diminished by SCCHN, fears of addiction, and an inability to cope with the additional losses associated with SCCHN. As a consequence, and perhaps, because of a failure the part of clinicians and patients to adequately address these fears, SCCHN patients may also experience greater psychological morbidity, becoming fatalistic about biomedicine's ability to restore them to health after cancer, or related symptoms, including pain, despite being 'cured.' This study provides a perspective on why this under-reporting occurs, thereby potentially enhancing clinician-patient communication and the QOL of SCCHN patients who present with curable disease.

Racial disparity in survival of patients with squamous cell carcinoma of the oral cavity and pharynx.

BACKGROUND: This study was designed to determine if race and age are independent prognostic factors for survival in patients treated for squamous cell carcinoma of the oral cavity and pharynx. METHODS: Retrospective study. RESULTS: Out of 909 patients registered, 815 (90%) were white and 94 (10%) were African-American. The median age was 60 years (range 19-93). The African-American patients had a significantly lower 5 year survival rate of 27.6% (95% CI 19.9-38.3) compared with white patients with a survival rate of 52.0% (95% CI 48.7-55.6) (P < 0.001). The greatest racial disparities in survival were observed in patients under 60 years of age [29.2% (95% CI 19.5-43.6) vs 60.9% (95% CI 56.3-66.0) for African-American and white patients, respectively, P < 0.001], and in African-American men compared with white men [20.2% (95% CI 12.6-30.2) vs 51.0% (95% CI 46.7-53.0), P < 0.001]. A multivariate Cox model, stratified according to stage of disease, indicated that race, age, and type of treatment were statistically significant predictors of survival. After adjusting for race and treatment received, African-American patients had a relative risk of dying of 1.61 (95% CI 1.23-2.10) compared with white patients. All patients 60 years of age and older had a higher risk of dying 1.59 (95% CI 1.31-1.92). Compared with surgical treatment alone, radiotherapy and other treatments were both associated with increased risk of dying with respective relative risks of 1.34 (95% CI 1.01-1.76) and 1.94 (95% CI 1.52-1.48). CONCLUSIONS: African-American patients had poorer survival outcomes, with race and age emerging as significant independent predictors of survival after treatment for oral and pharyngeal cancer, compared with their white counterparts. Primary and secondary prevention programs that target younger patients at high risk might reduce environmental risk factors such as smoking and alcohol consumption, which may play a greater role in the acquired susceptibility for oral and pharyngeal cancer in African-American males.

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Planning cancer prevention strategies based on epidemiologic characteristics: an Egyptian example.

BACKGROUND AND METHODS: We describe the epidemiology, cancer prevention strategies, and educational messages to be learned from four characteristic cancers in Egypt: urinary bladder, liver, lung, and early-onset colorectal cancers. RESULTS: For bladder cancer, effective and convenient treatment of schistosomiasis, using social marketing and mass media in public and medical education has contributed dramatically to primary prevention of bladder cancer in Egypt. For liver cancer, educating hospital administrators to remove structural barriers to good practice may help the control of hepatitis transmission and related liver cancer. For lung cancer, the 50-year American experience for controlling tobacco smoking, beginning with physicians, could be very effective in Egypt and other countries with increasing smoking rates in the young so as to avert the expected epidemics of lung cancer. For colorectal cancer, more attention to physician and public education about the importance of interviewing colorectal cancer patients about a family history of cancer and the screening of at-risk families could be very effective in early detection of colorectal cancer. CONCLUSION: Countries with similar cancer epidemiology experience should make use of successful cancer prevention and education strategies that could be translated from the Egyptian experience.

A voice that wraps around the body--communication problems in the advanced stages of non-small cell lung cancer.

INTRODUCTION: Significant problems in clinician-patient communication have been described in the oncology literatures. Advanced stage non-small lung cancer a devastating disease, can cause the communication between survivors, significant others, and clinicians to falter. To date, however, no studies have used qualitative methods to examine experiential aspects of living with non-small cell lung cancer. Nor have any studies evaluated the tools survivors might use to repair some of the damage caused by living with this disease. METHODS: Exploratory, two-part qualitative design. RESULTS: Survivors of non-small cell lung cancer live with multiple fears and losses. These include a diminished sense of self, the loss of health, fears of pain in a future tainted by the threat of death, and increased feelings of alienation due to the loss of previous sources of meaning in life. These experiences significantly affect cancer survivors abilities to communicate with clinicians and significant others. CONCLUSIONS: Survivors of non-small cell lung cancer often have difficulty sharing their experiences with others not suffering a similar affliction. Through their narratives with other survivors, however, patients are better able to initiate a biopsychosocial mechanism which enables them to create a cognitive map. This cognitive map helps survivors share their experiences with others, thereby repairing some of the damage caused by this disease, including the harm done to their communication with other people.

D2 dopamine receptor gene polymorphisms among African-Americans and Mexican-Americans: a lung cancer case-control study.

Recent research suggests that variant alleles (A1 and B1) of the DRD2 gene play a role in determining smoking status. However, no studies have evaluated these variant alleles in African-Americans and Mexican-Americans. The primary objective of this study, therefore, was to test the hypothesis that ever smokers in these ethnic groups are more likely than never smokers to have the DRD2 alleles associated with tobacco use (A1 and B1). Furthermore, because of a predicted higher prevalence of smokers in a family because of the patterns of inheritance of the genotypes associated with tobacco use, we also anticipated that individuals with these at-risk DRD2 alleles would be more likely to have a family history of smoking-related cancers. Because other inherited genetic variants may interact with smoking on cancer risk, we also hypothesized that this association might differ between cancer patients and control subjects. PCR was used to perform genotyping on peripheral WBC DNA from 140 lung cancer patients (43 Mexican-Americans and 97 African-Americans) and 222 age-, sex-, and ethnicity-matched controls (111 Mexican-Americans and 111 African-Americans). A personal family history was obtained from each participant. There were no statistically significant differences in the distribution of the DRD2 genotypes between cases and controls, although the frequency of the B1 genotype significantly differed by ethnicity (P = 0.002 for controls and P = 0.001 for cases). The DRD2 genotypes and smoking status showed a correlation among Mexican-American controls, although not among African-American controls. The cigarette pack-years in control subjects for the two ethnic groups combined were 30.8, 21.9, and 18.6 for the A1A1, A1A2, and A2A2 genotypes and 36.5, 20.8, and 18.5 for the B1B1, B1B2, and B2B2 genotypes, respectively. Similar trends were found for the number of cigarettes smoked per day among control subjects. From the standpoint of polymorphisms, however, there was a borderline significantly increased (3.6 times greater) frequency of smoking-related cancers among the first-degree relatives of case subjects with an A1 allele than among those without an A1 allele. There was also an elevated (1.8 times greater) frequency of smoking-related cancer among first-degree relatives of case subjects with a B1 allele compared with patients without a B1 allele, but this finding was not statistically significant. This phenomenon was not observed among control subjects. We noted a trend toward interaction of DRD2 A1 genotypes and case status for increased risk of smoking-related cancer among first-degree relatives. These findings suggest that the variant DRD2 genotypes are associated with a greater likelihood to smoke and a greater smoking intensity, as well as with a familial aggregation of smoking-related cancers. However, a large study is needed to confirm this finding.

Sun Protection is Fun! A skin cancer prevention program for preschools.

Children and their caregivers are prime candidates for intervention to curb the rising incidence of skin cancer in the United States. Preschools provide a unique opportunity to influence the sun protection practices of parents and teachers on behalf of young children. Sun Protection is Fun!, a comprehensive skin cancer prevention program developed by The University of Texas M. D. Anderson Cancer Center in collaboration with The University of Texas-Houston Health Science Center School of Public Health, was introduced to preschools in the greater Houston area. The program's intervention methods are grounded in Social Cognitive Theory and emphasize symbolic modeling, vicarious learning, enactive mastery experiences, and persuasion. Program components include a curriculum and teacher's guide, videos, newsletters, handbooks, staff development, group meetings designed to encourage schoolwide changes to support the program, and sunscreen. The intervention map, including objectives for program development, implementation, and evaluation, is discussed.

Perceived benefits of and barriers to participation in a phase I/II colon cancer chemoprevention trial.

METHOD: A questionnaire was administered to 42 subjects completing a one-year cancer chemoprevention trial (response rate = 69%, n = 29). The questionnaire assessed subjects' 1) previous study participation, 2) perceived benefits/barriers of participation, 3) likelihood of participating in future trials, 4) willingness to pay out-of-pocket expenses for trial participation, and 5) interest in post-trial continuation of the drug. RESULTS: The most highly rated benefits of trial participation were the possibility of reducing one's chance of getting cancer and the possibility of preventing others from getting cancer in the future. Barriers considered to be the most troublesome were billing problems and having colonoscopies done. Only 29% would have joined the trial had they been required to pay for trial-related costs. CONCLUSION: Results of this study may be used to educate potential participants about the benefits of/barriers to trial participation. Additionally, by learning from the experiences of trial participants, investigators can improve the execution of clinical trials, increasing participant satisfaction.

Social factors affecting interest in participating in a prostate cancer chemoprevention trial.

PURPOSE: A sample survey was conducted to assess the feasibility of recruiting participants, specifically African Americans, and to determine social factors influencing participation in a prostate cancer chemoprevention trial. METHODS: A convenience sample of adults visiting a hospital was identified and asked to participate in the survey. The survey included brief background information about prostate cancer and questions concerning four independent (age, marital status, race, insurance status) and three dependent (willingness to join a trial, involvement in long-term drug intake, interest in receiving more information) variables. RESULTS: The study analyzed 165 responses. Of the 165 respondents, 67% were African American. Marital status was a significant predictor of general willingness to participate (p = 0.047) for male respondents. No significant predictor was found for female respondents. Furthermore, for men, ethnicity/race showed a significant difference (30% white men vs 70% of minority men) for willingness to take the pills. CONCLUSION: The results suggest that African Americans are receptive to participating in chemopreventive trials. Thus, future studies exploring chemoprevention trials as an effective tool for reaching African Americans are warranted.

Durability and diffusion of the nutrition intervention in the Working Well Trial.

BACKGROUND: The Working Well Trial (WWT) emphasized employee participation in the planning and implementation of the health promotion intervention. These participatory strategies were intended to promote institutionalization of the health promotion program and thereby encourage maintenance of the intervention activities. We used data from 107 worksites in the WWT to test whether the nutrition intervention activities were maintained after the research program (i.e., durability) or were adopted by control sites (i.e., diffusion). METHODS: At baseline, upon the completion of the 2-year intervention, and 2 years later, we conducted organization surveys regarding worksite health promotion activities. A nutrition activity score from 0 to 3 was calculated based on availability of nutrition-related programs, self-help manuals or guides, and videos, tapes, brochures, or posters. RESULTS: From baseline to the end of the intervention, there was a significant increase in the nutrition activity score in intervention worksites compared with the controls (P < 0.001). However, 2 years later, there was no difference between intervention and control worksites. In addition, there was no significant increase in the nutrition activity score in control site 2 years after they received the intervention protocols and materials. CONCLUSIONS: Research is needed to develop and test worksite-based interventions to promote institutionalization, durability, and diffusion.

Cigarette smoking in a multiethnic population of youth: methods and baseline findings.

BACKGROUND: To expand upon recent research studies that have identified dramatic ethnic differences in adolescent cigarette smoking, this study was designed to characterize smoking among a multiethnic population of adolescents and to identify significant factors that may protect against smoking initiation. METHODS: During the first 2 years, this mixed cross-sectional, longitudinal study recruited and collected baseline data from a volunteer sample of 1,441 Houston-area public school students in the 5th, 8th, or 12th grade. A wide range of new and established predictors of smoking behavior was assessed, and their associations with ever smoking and susceptibility to smoking were assessed within ethnicity (white, N = 537; African-American, N = 454; and Hispanic, N = 297). RESULTS: Consistent with previous studies, white students smoked in substantially higher proportions than African-American students, with Hispanic adolescents in-between. Simultaneously adjusting for other variables, the odds of ever smoking (OR = 0.47, P < 0.01) and susceptibility to smoking (OR = 0.64, P < 0.01) were significantly lower among African-American adolescents when compared with whites; odds ratios for Hispanics and whites did not differ. Across all three ethnicities, the most important predictor of both ever smoking and susceptibility to smoking was the smoking status of the three best friends. Several ethnicity-specific variables also were identified. CONCLUSIONS: In concordance with previous investigations, cigarette smoking prevalence differs by ethnicity, and the factors associated with ever smoking and susceptibility to smoking differ among white, African-American, and Hispanic adolescents. The results of this study may be used to develop theory-based, culturally appropriate smoking intervention programs for adolescents.

Case-control study of the D2 dopamine receptor gene and smoking status in lung cancer patients.

BACKGROUND: Interindividual differences in the structure and expression of the dopamine receptor genes affect dopamine availability and may be the genetic basis for variation in vulnerability to tobacco smoking. In this study, prevalences of polymorphisms in the TaqIA allele (A1 and A2) and the TaqIB allele (B1 and B2) of the D2 dopamine receptor gene in 157 lung cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A1 and B1 alleles are more vulnerable to nicotine addiction. METHODS: Case and control subjects were accrued from an ongoing epidemiologic study. Blood samples were collected from them and subjected to molecular genetic analyses. Subjects were interviewed to obtain relevant information. Current and former smokers were administered a questionnaire to quantify their addiction to nicotine. RESULTS: The combined B1B2 genotypes appeared to be more prevalent in ever smokers than in never smokers among case patients (30.3% versus 13.3%; two-sided P = .233) and among control subjects (30.9% and 0%; two-sided P = .02); statistically significant differences were not observed among those with A1 genotypes. Statistically significant correlations between the presence of the A1 and B1 alleles were observed (r = .73 for case subjects and r = .76 for control subjects; two-sided P<.001). Individuals with rarer genotypes reported having been substantially younger at the time of smoking initiation (statistically significant for both A1 and B1) and having attempted to quit smoking fewer times (statistically significant for only A1). CONCLUSION: Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.

Sociodemographic analysis of patients in radiation therapy oncology group clinical trials.

PURPOSE: To assess the degree to which the sociodemographic characteristics of patients enrolled in Radiation Therapy Oncology Group (RTOG) clinical trails are representative of the general population. METHODS AND MATERIALS: Sociodemographic data were collected on 4016 patients entered in 33 open RTOG studies between July 1991 and June 1994. The data analyzed included educational attainment, age, gender, and race. For comparison, we obtained similar data from the U.S. Department of Census. We also compared our RTOG data with Surveillance Epidemiology and End Results (SEER) data for patients who received radiation therapy, to determine how RTOG patients compared with cancer patients in general, and with patients with cancers at sites typically treated with radiotherapy. RESULTS: Overall, the sociodemographic characteristics of patients entered in RTOG trials were similar to those of the Census data. We found that, in every age group of African-American men and at nearly every level of educational attainment, the proportion of RTOG trial participants mirrored the proportion in the census data. Significant differences were noted only in the youngest category of African-American men, where the RTOG accrues more in the lower educational categories and fewer with college experience. For African-American women, we found a similar pattern in every age group and at each level of educational attainment. As with men, RTOG trials accrued a considerably larger proportion of younger, less educated African-American women than the census reported. Using SEER for comparison, the RTOG enrolled proportionately more African-American men to trials all cancer sites combined, and for prostate and head and neck cancer. In head and neck trials, the RTOG enrolled nearly twice as many African-American men than would be predicted by SEER data. In lung cancer trials, RTOG underrepresented African-American men significantly; however, there was no difference for brain cancer trials. There were no racial differences in RTOG accrual and SEER incidence data for women on trials in brain, lung, and head and neck cancer. However, the RTOG trials accrued nearly twice the proportion of African-American women in cervical cancer trials and in all sites combined, compared to the SEER data. CONCLUSIONS: Comparisons with the U.S. Census and SEER show that African-Americans are proportionally well represented in cancer clinical trials conducted by the Radiation Therapy Oncology Group. The comparative analysis indicates that all educational levels in each age group of African-Americans generally mirror the U.S. Census, with one exception. The exception is a significant overrepresentation of less-educated African-Americans in the youngest age category. This exception is counter to the expectation that better-educated patients are more likely to enroll in trials. When compared with SEER data, the RTOG trials either parallel or overrepresent African-American men and women, with the only exception being in lung cancer, where men are underrepresented. These results show that, in comparison to the Census and SEER data, the RTOG has fulfilled its commitment to enroll African-American patients in its clinical trials.

Correlates of mutagen sensitivity in patients with upper aerodigestive tract cancer.

Although tobacco and alcohol use are the major determinants of upper aerodigestive tract carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens. One explanation may be differences in mutagen sensitivity (as measured by the in vitro bleomycin-induced mutagen sensitivity assay) in patients with squamous cell carcinoma of the upper aerodigestive tract. Antioxidant supplementation has also been shown to decrease DNA damage and thus may also inhibit carcinogenesis. In this study, we examined whether smoking, alcohol intake, and dietary antioxidant intake were correlated with mutagen sensitivity. The 612 patients evaluated are part of an ongoing multicenter Phase III trial of 13-cis retinoic acid for the prevention of second primary tumors. We found that patients with pharyngeal cancers were more likely than patients with oral cavity or larynx cancers to be mutagen sensitive. There were no significant differences in the distribution of mutagen sensitivity by sex or alcohol use. Never smokers were significantly more likely (61.1%) to be mutagen sensitive than current smokers (35.6%). Dietary consumption of the micronutrients alpha-carotene, beta-carotene, lutein, lycopene, and vitamin C was not correlated with mutagen sensitivity. Therefore, we suggest that mutagen sensitivity is an independent marker of cancer risk not affected by other known risk factors.

Identifying and recruiting healthy control subjects from a managed care organization: a methodology for molecular epidemiological case-control studies of cancer.

Case-control studies with stringent matching criteria require large pools of healthy subjects from which to select matched controls. This paper describes a successful method of identifying a large pool of potential control subjects to participate in two molecular epidemiological case-control studies of lung cancer, each enrolling 400 case subjects and 400 control subjects. These studies are not population based, and the study base is not well-defined. Therefore, potential control subjects are being identified and recruited through 20 area clinic sites of a large multispecialty health maintenance organization. Because the research focus is driven by genetic hypotheses and we are controlling for multiple smoking-related variables, representativeness is of lesser concern. To identify potential control subjects, a one-page questionnaire is distributed to patients in the waiting room to assess contact information as well as data relevant to the case-control matching process. An average of 2,228 questionnaires are returned monthly toward a target pool of 40,000; of these, 59% of the respondents fulfill eligibility criteria as a control subject for one of the studies and are not averse to being contacted in the future for the purpose of research. When compared to former smokers and never smokers, current smokers in the control population were least likely to refuse further contact. A collaborative arrangement with a managed care organization offers a feasible mechanism through which researchers can access a large, ethnically diverse population of potential control subjects.