Biomedical subjects

M R Spitz

Publications and source records attributed to M R Spitz.

173 records · Page 10Linked to original sources

PubMedDate not supplied

Incidence of salivary gland cancer in the United States relative to ultraviolet radiation exposure.

There is biologic and histogenetic plausibility for an association between salivary gland cancer and nonmelanoma skin cancer. To add further credence to this association, a descriptive epidemiologic study of salivary gland cancer incidence data from the Surveillance Epidemiology and End Results (SEER) program from 1973 to 1981 was undertaken. The objective was to determine whether the incidence of this cancer exhibited the inverse association with geographic latitude that is characteristic of skin cancer incidence. The SEER areas were grouped into three regions (north, central, and south), based on indices of ultraviolet radiation. The southern area had significantly higher rates for white males and females compared with the northern area for all histologic subtypes combined (standardized incidence ratios were 1.6 for males and 1.4 for females), as well as for specific histologic subtypes (adenocarcinoma, squamous cell carcinoma, and males only with mucoepidermoid carcinoma). However, there were no significant differences in incidence between the central and northern areas. These data provide further evidence of an association between skin and salivary neoplasms, both exhibiting a pattern of incidence suggestive of susceptibility to ultraviolet radiation exposure.

Environmental Exposure↗

PubMedDate not supplied

The role of DNA repair capacity in susceptibility to lung cancer: a review.

Human cancer risk assessment has relied largely on animal experiments and use of short-term biological tests based on chemical-DNA interaction. The recent introduction of biomarkers to molecular epidemiologic studies has provided another means of assessing risk for tobacco-related cancer. Several biomarkers for genetic susceptibility to lung cancer have been developed and validated in pilot studies that have demonstrated their association with increased risk of lung cancer. For instance, metabolic enzymes responsible for bioactivation and detoxification of environmental chemicals, carcinogen-induced DNA adducts and chromosomal aberrations, and host DNA repair capacity have been measured in human peripheral lymphocytes. These markers allow estimation of interindividual variation in response to carcinogen exposure and thus assessment of cancer risk. Therefore, epidemiological studies of exposure and of molecular etiology of human carcinogenesis provide a new avenue of cancer risk assessment.

DNA Repair↗

PubMedDate not supplied

Multiple primary cancer risk in patients with major salivary gland carcinoma.

The subsequent primary cancer experience of 498 patients with major salivary gland carcinoma was evaluated using a life-table approach. Expected numbers were generated from two sources. These were population-based tumor registry data and an internal comparison group of randomly selected individually matched patients drawn from the same institution. Compared with either referent group, elevated risk ratios for all cancer sites combined were demonstrated. Risks for subsequent lung cancer were raised but were not statistically significant. For subsequent skin cancer, significantly elevated risks were noted.

Female↗

PubMedDate not supplied

Ethyl alcohol as a cocarcinogen with special reference to the aerodigestive tract: a cytogenetic study.

Although prior to its metabolic conversion alcohol has no mutagenic activity, an interaction of alcohol with tobacco in carcinogenesis of the head and neck region is well characterized. In a recent ecogenetic case control study of these cancers we documented an interaction between alcohol use and in vitro mutagen-induced chromosome damage in cancer risk. The present report evaluates the in vitro genotoxicity of five mutagens (including cigarette smoke condensate) tested in conjunction with 2% and 4% ethanol in human lymphoid cell lines. Ethanol alone did not exert a demonstrable clastogenic effect, as measured by the frequency of chromatid breaks per cell. However, the clastogenic potential of all mutagens increased when ethanol was added concurrently with the mutagens, and there was a dose-dependent potentiation of clastogenicity by ethanol, with a threshold dose between 0.5% and 1.0%. Preliminary experimental results strongly indicate that ethanol, at relatively high doses, inhibits DNA and chromosome repair systems. These data support the epidemiologic evidence of an interaction between alcohol and mutagens in carcinogenesis and suggest that alcohol may have co-carcinogenic properties.

Bleomycin↗

PubMedDate not supplied

Mutagen sensitivity: a biological marker of cancer susceptibility.

We intend to continue our exploration of the bleomycin assay as a biological marker for the development of environmentally induced cancers. The impetus for such efforts would be enhanced through effective integration of cancer screening and intervention to achieve diminished cancer mortality. Currently, we are integrating combining bleomycin sensitivity screening to chemopreventive therapy against second primary malignancies in head and neck cancer patients. Previous studies have demonstrated that cis-retinoic acid, the agent used in our chemopreventive trial, is effective in such circumstances (35). Our purpose is to identify a high-risk subpopulation through application of the bleomycin sensitivity assay and then demonstrate that we can modulate the carcinogenic process with cis-retinoic acid. The use of genetic markers clearly enhances the power and precision of epidemiological research. The preventive implications of precise and valid markers for carcinogen sensitivity are obvious. We are aware of the need for extensive validation of the assay and for rigorously designed and conducted epidemiological studies. The strength of the association between cancer risk and mutagen sensitivity, despite the inherent problems in the size and design of the studies, is noteworthy. The thesis that chromosome instability and defective DNA repair may underlie susceptibility to environmental carcinogenesis is plausible and presents a promising avenue for further multidisciplinary research.

Alcohol Drinking↗

PubMedDate not supplied

The development of a comprehensive, institution-based patient risk evaluation program: I. Development, content, and data management.

There is a need for standardization of risk factor questionnaires for epidemiological research. This paper describes the development and implementation of a comprehensive cancer risk evaluation program at the University of Texas M.D. Anderson Cancer Center. A detailed self-administered questionnaire is given to all newly registered adult patients. The format of the instrument, coding systems, quality control measures, and data entry mechanisms are discussed. The criteria for the choice of a data base management system are outlined. The identification of high-risk patient subgroups is possible, and it is feasible to link this data base with clinical and biochemical data. There is considerable potential for collaborative research using this risk evaluation program, bringing together basic scientists, clinicians, and epidemiologists.

Cancer Care Facilities↗

PubMedDate not supplied

The development of a comprehensive, institution-based patient risk evaluation program: II. Validity and reliability of questionnaire data.

The accuracy of historical information derived from self-administered questionnaires must be confirmed. We report the results of studies conducted to assess the reliability and validity of data collected from a comprehensive cancer risk factor questionnaire developed at The University of Texas M.D. Anderson Cancer Center. A comparison of the basic demographic data of a randomly selected sample of 80 respondents and 70 nonrespondents revealed no fundamental ethnic or socioeconomic differences. We verified self-reported past illnesses, surgical procedures, and cancers by reviewing 72 patient charts, using stringent diagnostic criteria for verification. We noted substantial agreement between self-reported and documented illnesses and operations. With the exception of nine patients who misclassified metastatic disease, the verification of primary cancers was excellent. We determined reliability by interviewing 50 of these patients by telephone. Questions with a dichotomous outcome (e.g., smoking status) were reliably answered; however, those requiring quantification (e.g., amount of alcohol consumed) were less accurately reported on interview. While we recognize the limitations of self-administered questionnaires, we believe this program will develop into a comprehensive, standardized, easily accessible patient risk factor data base.

Cancer Care Facilities↗

PubMedDate not supplied

Association between family history of cancer and mutagen sensitivity in upper aerodigestive tract cancer patients.

This study evaluated the relationship between family history of cancer and bleomycin-induced mutagen sensitivity. The study included 108 patients who registered at The University of Texas M.D. Anderson Cancer Center from June 1987 to June 1991 with histologically confirmed and previously untreated squamous cell carcinoma of the upper aerodigestive tract. All patients underwent the mutagen sensitivity assay and completed a self-administered risk evaluation questionnaire, including a detailed family history. The patients reported having 650 first-degree relatives, including 54 cases with cancers. The patients were classified as mutagen sensitive (> or = 1 chromosome break/cell) or not mutagen sensitive (< or = 0.99 chromosome breaks/cell). Odds ratios (ORs) were calculated to test for significant associations between mutagen sensitivity and family history of cancer. We found a significant OR (OR = 2.63; 95% confidence interval = 1.06-6.53) for patients who were mutagen sensitive and had one first-degree relative affected with cancer. For mutagen-sensitive patients with two or more first-degree relatives affected with cancer, the OR increased to 6.59 (95% confidence interval = 1.69-25.72). Although 88% of the patients were ever smokers, cigarette smoking was not found to be related to mutagen sensitivity. The study findings suggest that patients who have defective DNA repair capability as evidenced by the mutagen sensitivity assay are significantly more likely to report a family history of cancer than patients who are not mutagen sensitive. Further studies are needed to confirm that mutagen-sensitive individuals have inherited an increased risk of cancer.

Adult↗

PubMedDate not supplied

Mutagen sensitivity in upper aerodigestive tract cancer: a case-control analysis.

Variability in DNA repair capability may be a determinant of interindividual difference in susceptibility to carcinogenic exposures. A cytogenetic assay which quantifies chromosomal breakage induced by in vitro exposure to a clastogen provides an indirect measure of repair. We report the results of a case-control study of upper aerodigestive tract cancers assessing differences in mutagen sensitivity based on this assay. There were 108 cases with previously untreated squamous cell cancers and 108 age and sex frequency-matched controls selected from blood donors to The University of Texas M. D. Anderson Cancer Center. Sixty-nine% of the cases, compared with 44% of the controls, were classified as mutagen sensitive (breaks per cell > or = 0.8). On multivariate analysis, mutagen sensitivity [odds ratio (OR), 2.5], heavy cigarette smoking (OR, 4.8), and heavy alcohol consumption (OR, 3.1) were associated with significantly increased risk. Stratified analyses showed that the combined effects of cigarette smoking (OR, 8.1) and mutagen sensitivity (OR, 3.2) were suggestive of a multiplicative effect (OR, 23.0). The combined estimate for alcohol use (OR, 3.0) and mutagen sensitivity (OR, 3.0) was 5.8. These data confirm those of a previously published preliminary study of upper aerodigestive cancers and underscore the importance of considering interindividual susceptibility in cancer risk characterization, even for those cancers with well quantified exposures.

Alcohol Drinking↗

PubMedDate not supplied

Genetic susceptibility to lung cancer as determined by lymphocytic chromosome analysis.

Chromosomal anomalies were analyzed in the lymphocyte cultures among 96 untreated lung cancer patients and 74 clinically normal comparison subjects. The analysis revealed that >15% of the lung cancer patients showed structural or numerical rearrangements in chromosomes 1,3,5,7,9,12,14, and 21. A case control comparison showed that these aberrations were significantly higher in chromosome 7 [odds ratio (OR) = 2.32; 95% confidence interval (CI), 1.14 and 4.82], chromosome 9 (OR = 2.61; 95% CI, 1.27 and 5.48), chromosome 12 (OR = 4.10; 95% CI, 1.40 and 14.54), and chromosome 21 (OR = 7.75; 95% CI, 1.73 and 70.80) of the patients than in the controls. However, only chromosome 9 (OR = 3.57; 95% CI, 1.33 and 9.46) and chromosome 21 (OR = 6.94; 95% CI, 3.15 and 9.98) retained significance after stratifying on smoking status. Among the lung cancer patients, the breakpoints cluster in specific regions of some of these chromosomes. These regions are 1p13-q21, 3q21-q13, 7p12-q12, 7q12-q12,7q22, 7q32, 9p13-q13, 12p13, 14q11, and 14q32. The distribution of lung cancer patients, according to histological types, showed that aberrations in chromosomes 1,7, and 9 dominated the scenario of chromosomal changes in non-small cell lung carcinomas. Thus, the data on lymphocytic chromosomal rearrangements in lung cancer patients not only indicate the importance of specific genetic changes in the etiology of lung cancer but also emphasizes the putative role of such analysis in determining primary genetic abnormalities in the large heterogeneous group of lung cancers.

Case-Control Studies↗

PubMedDate not supplied

Fluorescent in situ hybridization analysis in blood lymphocytes of lung cancer patients.

Genetic predisposition to lung cancer was determined by observing nonrandom chromosomal alterations in peripheral blood lymphocytes (PBLs) of lung cancer patients. The histological distribution of the cases showed that chromosomes 7 and 9 were frequently altered in squamous cell lung carcinoma (SCLC) patients. We analyzed PBLs of 26 SCLC patients and 5 controls using fluorescent in situ hybridization (FISH) with whole chromosome painting probes of chromosomes 7 and 9 to further investigate the frequency of rearrangements in these chromosomes. Our results suggested that seeking nonrandom aberrations in larger numbers of cells using FISH strengthened our previous observation of mosaicism and involvement of specific chromosomes in lung cancer patients. On combining our previous data, aberrations in chromosome 7 (16 of 26 patients), chromosome 9 (14 of 26), and the present study, we could actually pinpoint more individuals with abnormalities of chromosome 7 (23 of 26) and chromosome 9 (21 of 26). Thus, analyzing more cells in PBLs and adding FISH analysis serve as useful adjuncts to our studies of nonrandom chromosomal aberrations and genetic mosaicicm.

Adult↗