Biomedical subjects

M R Spitz

Publications and source records attributed to M R Spitz.

At least 109 records · Page 6Linked to original sources

PubMed1996

Correlation between selected environmental exposures and karyotype in acute myelocytic leukemia.

Many bone marrow cytogenetic abnormalities in acute myelogenous leukemia (AML) are tumor specific, clonal, nonrandom, and related to prognosis; it has been hypothesized that they may be markers of exposure to etiological agents. A previous report from our institution revealed several such associations; the purpose of the current study was to determine whether previous findings were present in a new group of patients. Subjects included 84 newly diagnosed AML patients (French-American-British M1 and M2); exposure data were gathered using self-report questionnaires at the time of registration. Two sets of comparisons were made: (a) patients with all (AA) or some (AN) cytogenetically abnormal cells versus those with normal karyotypes (NN) and (b) patients with specific abnormalities [-5/5q-, -7/7q-, +8, t(8;21)] versus all others. Odds ratios (ORs) were 4.64 for the association between prior cytotoxic therapy and -5/5q- and 6.38 for the association with -7/7q-, but were <1.00 for +8 and t(8;21). There were no ORs > 2.0 for specific abnormalities in any of the other exposures evaluated (cigarette smoking, alcohol use, occupational exposure to organic chemicals, paints, or pesticides/herbicides), with the exception of exposure to paints and -7/7q- (OR, 7.50). The ORs for AA/AN versus NN patients were 1.43 and 3.81 for smoking and alcohol use, and weak dose-response trends were present. The most consistent positive associations between the two series were for prior cytotoxic therapy (-5/5q-; -7/7q-), cigarette smoking (AA/AN versus NN) and alcohol use (AA/AN versus NN). Reasoning from the known association between prior cytotoxic therapy and -7/7q-, we would have predicted relatively high ORs (> 4.0) if specific abnormalities acted as markers for the exposures assessed, but none were present. However, in both series, AA/AN patients were more likely to smoke and use alcohol than were NN patients, and weak dose-response patterns were present for both. This finding suggests that both smoking and alcohol use may play a role in the pathogenesis of cytogenetic abnormalities in AML-M1/M2; however, the mechanism by which they work and whether they are involved in the etiology of these diseases remain unclear.

Adult↗

PubMed1996

Survival of cells with bleomycin-induced chromosomal lesions in the cultured lymphocytes of lung cancer patients.

In a previous study of lung cancer, we showed that bleomycin, a radiomimetic agent, induced breaks preferentially on chromosomes 4 and 5. The molecular cytogenetic study reported here, using chromosome painting and G banding, was designed to assess whether the chromatid breaks induced by bleomycin could survive as chromosome-type aberrations after treated lymphocyte populations were allowed to recover in a drug-free medium for one or two cell generations and whether the survival rates of lesions on chromosomes 4 and 5 differed in cases with lung cancer and controls. The findings from 16 cases and 14 controls showed that in samples allowed to recover for 48 h, most aberrations were of the chromosome type. The proportion of chromosome 5 abnormalities surviving as chromosome-type aberrations was significantly higher in the cells of lung cancer cases (13.4%) than in controls (4.6%; P < 0.0001). However, no significant differences in survival of chromosome 4 abnormalities were detected between cases and controls. The proportions of chromosome 5q13-q22 abnormalities were 5.3% in the cases and 0.6% in the controls (P < 0.0001). 5q13-q22 regions encompassed 38.4% of all abnormalities on chromosome 5 in the cases but only 14.5% in the controls. Therefore, the survival rate of chromosome 5 lesions (especially those at 5q13-q22) in lymphocytes might be used as a biomarker to identify populations at high risk for lung cancer.

Antibiotics, Antineoplastic↗

PubMed1996

Mutagen sensitivity exhibits a dose-response relationship in case-control studies.

We have been quantitating, as a marker of cancer susceptibility, induced chromatid breaks in lymphocyte cultures exposed to chemical mutagens. This report highlights the consistency of the results from two case-control studies, using different methods of presenting the data. In both the lung cancer case-control study, which used bleomycin, a radiomimetic agent, as the test mutagen, and the melanoma study, which used 4-nitroquinoline-oxide, an UV-mimetic agent, the mean number of breaks/cell was significantly higher in the cases compared with the controls. When the data were dichotomized at the 75th percentile of breaks in the control populations, significantly elevated adjusted odds ratios (3.7 and 5.0, respectively) were detected. Dose-response relationships were evident in both studies when the data were categorized by quartiles of breaks/cell in the controls, with highest risk estimates being in the top quartile of induced breaks. The potential for extending this assay to other cancer sites, using a variety of test mutagens, is exciting.

4-Nitroquinoline-1-oxide↗

PubMed1996

A statistical analysis of the reliability and classification error in application of the mutagen sensitivity assay.

In vitro mutagen hypersensitivity, determined with the bleomycin assay, has been found to be an independent risk factor for developing primary upper aerodigestive tract cancers, lung cancers, and second malignant tumors. The average number of chromatid breaks per cell (b/c) is derived from evaluating an arbitrarily set number of metaphases (usually 50) in each sample. The reliability of such an approach is of key importance in large-scale epidemiological studies. Because evaluating metaphases is a time-consuming task, it is desirable to know the minimum number of readings needed to reach an acceptable reliability. Statistical analyses were performed in 160 observations for which b/c values were determined by the same observer scoring 100 consecutive metaphases per sample. The b/c values were between 0.14 and 1.30 (mean, 0.61). The b/c values were separately calculated for the first and second sets of 50 metaphases. There was essentially no difference in the mean b/c values between the first and second 50 readings (difference, -0.002). The correlation between the two sets of readings was 0.72. The SE of the b/c values, based on scoring 50 metaphases, was 0.15. When scoring 100 metaphases, the SE decreased to 0.11. After evaluating the first 50 metaphases, the theoretical gain in reducing the SE was <1% with each additional reading. When 0.8 was used to dichotomize the mean b/c value into bleomycin-resistant or bleomycin-hypersensitive groups, sensitivity and specificity of reading 50 metaphases were above 75% and 95% when compared to 100 readings. A simulated case control study showed that there is a 15% attenuation in estimating the odds ratio with 50 readings. The findings suggest that the conventional method of reading 50 metaphases can yield an acceptable reliability in our setting and may be applied to other cancer epidemiology studies.

Algorithms↗

PubMed1996

DNA repair capacity correlates with mutagen sensitivity in lymphoblastoid cell lines.

This study describes a correlation between cellular DNA repair capacity and the frequency of mutagen-induced in vitro chromosomal breaks in selected lymphoblastoid cell lines. Two assays, host cell reactivation (HCR) assay for measuring cellular DNA repair capacity and in vitro mutagen sensitivity assay, have recently been shown to be useful biomarkers for such susceptibility. Increased in vitro mutagen sensitivity, measured by the number of induced chromatid breaks, has been postulated to reflect decreased capacity of DNA repair, as measured by the HCR assay. However, these two assays have not been examined in parallel to test this hypothesis. In this study, we performed both assays in 16 established lymphoblastoid cell lines derived from patients with xeroderma pigmentosum (n = 3), ataxia telangiectasia (n = 2), head and neck cancer (n = 3), and melanoma (n = 2), and from normal human subjects (n = 6) using UV light, 4-nitroquinoline-1-oxide (4-NQO; an UV-mimetic agent), and gamma-irradiation as the test agents. The measurements from the HCR assay correlated significantly with the frequency of chromatid breaks induced by either UV irradiation (r = -0.69; P < 0.01) or 4-NQO (r = -0.70; P < 0.01). Although published data suggest that damage induced by UV and 4-NQO may be repaired by different pathways, the two agents induced similar frequencies of chromatid breaks (r = 0.68; P < 0.01) in the tested cell lines. Our results also indicated that the HCR assay is not suitable to test agents that cause DNA strand breaks, such as gamma-irradiation, whereas the mutagen sensitivity assay is. Although reduced cellular DNA repair capacity correlated with increased frequency of mutagen-induced chromatid breaks in these cell lines, these two assays have different sensitivities in measuring the repair of damage induced by different carcinogens; therefore, the use of both assays is recommended for future molecular epidemiological studies of cancer susceptibility.

4-Nitroquinoline-1-oxide↗

PubMed1996

Mutagen sensitivity as a marker of cancer susceptibility.

Modulation of environmental exposures by host genetic factors may explain interindividual variation in susceptibility to carcinogenesis. One determinant of susceptibility is mutagen sensitivity measured by the frequency of bleomycin-induced breaks in an in vitro lymphocyte assay. Mutagen sensitivity is a significant predictor of aerodigestive tract cancer risk. In this case-control study of lung-cancer susceptibility markers, 54% of 132 lung-cancer cases had mutagen-sensitivity scores greater than or equal to 1 break/cell, compared with only 22% of 232 controls. The mean breaks/cell value (+/-SE) for the 88 African-American cases was 1.11 (+/-0.60), compared with 0.82 (+/-0.49) for the 121 controls (P < 0.001). For the 44 Mexican-American cases and 111 controls, the comparable values were 1.11 (+/-0.52) and 0.76 (+/-0.38), respectively. The overall odds ratio (OR) for mutagen sensitivity (dichotomized at > or = 1 break/cell), after adjusting for ethnicity and smoking status, was 3.62 (95% confidence limits [CL] = 2.2, 5.9). For current smokers the adjusted risk associated with mutagen sensitivity was 2.52 (1.2, 5.3). For former smokers, the comparable OR (95% CL) was 6.19 (2.7, 14.1). The risk estimate for those under 61 years of age was 4.85 (2.3, 10.4), compared with 2.85 (1.5, 5.6) for older subjects. The risk also appeared to be higher for lighter smokers (< 20 cigarettes daily) than heavier smokers (ORs = 5.72 and 3.20, respectively). The ethnicity-adjusted ORs by quartile of breaks/cell were 1.0, 1.40, 2.46, and 4.80; the trend test was significant at P < 0.001. The joint effects of mutagen sensitivity and former smoking, current smoking, or heavy smoking were greater than additive, although the interaction terms were not statistically significant in the logistic model. Mutagen sensitivity may therefore be a useful member of a panel of susceptibility markers for defining high-risk subgroups for chemoprevention trials.

Adult↗

PubMed1995

p53 mutations in nonmelanoma skin cancer of the head and neck: molecular evidence for field cancerization.

Multiple and distinct p53 mutations were detected by DNA sequence analysis in tumor and adjacent nonmalignant skin samples from eight patients with nonmelanoma skin cancer of the head and neck, providing unambiguous evidence for field cancerization. The mutations consisted of C-->T transitions at dipyrimidine sequences (30% of all single base substitutions), T-->C transitions (47%), and G-->T transversions (12%), suggesting that other carcinogens may act along with UV radiation in the development of nonmelanoma skin cancer. Patient interviews revealed that, in addition to substantial exposure to solar UV radiation, most had a history of smoking and were exposed to carcinogens from industrial or agricultural sources. These data show that extensive molecular epidemiological investigations are necessary to elucidate risk factors associated with the disease in localities where patients often report substantial exposure to environmental carcinogens.

Adult↗

PubMed1995

A case-control study of nonrandom distribution of bleomycin-induced chromatid breaks in lymphocytes of lung cancer cases.

We used a case-control study design to determine the association between bleomycin-induced chromatid breaks and the risk of lung cancer in general and by specific histopathological types. Lymphocytes from primary blood cultures of 78 controls and 75 cases with 4 histopathological types of lung cancer were treated with 0.03 unit/ml bleomycin for 5 h, and the frequency of induced chromatid breakage and the locations of the breaks were determined in Q-banded preparations. After adjustment for their length, the larger chromosomes had more breaks than the smaller chromosomes in both cases and controls. The cases had significantly more breaks on chromosomes 4 and 5 than the controls did, with odds ratios (ORs) of 4.9 [95% confidence limits (CL), 2.0, 11.7] and 3.9 (95% CL, 1.6, 9.3), respectively. When the lung cancers were classified by histopathological type, adenocarcinomas had significantly more breaks on chromosomes 4 and 5, with ORs of 3.0 (95% CL, 1.0, 8.7) and 3.5 (95% CL, 1.2, 10.7), respectively. For squamous cell carcinoma, the ORs were significantly elevated for breaks on chromosomes 2, 4, and 5 with ORs of 3.5 (95% CL, 1.0, 11.7), 10.2 (95% CL, 2.5, 41.9), and 7.9 (95% CL, 1.9, 32.8). For small cell carcinoma, breaks on chromosomes 2 and 4 showed significantly increased ORs of 33.2 (95% CL, 2.2, 513.3) and 20.4 (95% CL, 1.7, 250.1), respectively. However, no specific chromatid breaks were detected in cases with large cell carcinoma. When the frequency of chromatid breaks at specific regions was calculated, breaks at 4p14, 4q27, 4q31, 5q21-q22, 5q31, and 5q33 were significantly more common in lung cancer cases than in controls. Lung cancer risk had a dose-response relationship with breaks on chromosomes 4 and 5. Cigarette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5. The findings suggest that the susceptibility of particular chromosome loci to mutagenic damage may be a risk factor for specific types of lung cancer.

Adenocarcinoma↗

PubMed1995

Risk factors and genetic susceptibility.

Tobacco use is such a major determinant of head and neck cancer risk that classical epidemiologic techniques were more than adequate to document and characterize the etiologic association. However, the new emphasis in epidemiologic research is multidisciplinary, centering on the role of interindividual differences in susceptibility to carcinogenic exposures and particularly on the interaction of genetic susceptibility and environmental forces, that is, ecogenetics. For upper aerodigestive tract cancers, measurements of carcinogen metabolic activation and DNA repair capability are especially relevant. These susceptibility markers will enable the identification of high-risk population subgroups who can be targeted for the most intensive primary and secondary preventive strategies.

Animals↗

PubMed1995

Glutathione s-transferase genotypes as risk factors for head and neck cancer.

BACKGROUND: Several enzymatic systems, including glutathione S-transferases, are involved in the metabolism of environmental agents. The absence of glutathione S-transferases mu (GSTM1) and theta (GSTT1) results in decreased detoxification of carcinogens, for example, chemicals in cigarette smoke. These metabolic deficiencies may predispose individuals to the development of smoking-related tumors, such as cancers of the lung, head and neck, and bladder. METHODS: The glutathione S-transferase genotypes of 186 previously untreated patients with squamous cell carcinoma of the head and neck and 42 healthy controls were determined with polymerase chain reaction (PCR) methodologies. Lymphocytes separated from heparinized peripheral blood or whole blood extracts served as sources of genomic DNA. The presence or absence of the gene-specific PCR products revealed the positive or negative genotypes, respectively. RESULTS: The absence of the GSTM1 genotype conferred an odds ratio of 2.37, and the 95% confidence interval (CI) was 1.20 to 4.67. The absence of the GSTT1 gene conferred an odds ratio of 1.47 (CI 0.71 to 3.02). In the population of 42 patients and their matched 42 controls, the absence of the GSTM1 and GSTT1 genotypes conferred odds ratios of 3.10 (CI 1.24 to 7.75) and 2.18 (CI 0.91 to 5.23), respectively. CONCLUSIONS: Despite the small study size, our preliminary data suggest that genetically determined factors of carcinogen metabolism may be associated with increased risk for head and neck cancer.

Base Composition↗

PubMed1995

Improving residents' knowledge of cancer prevention: are physicians prepared for prevention?

BACKGROUND: Primary care physicians recognize the goal of integrating cancer-prevention strategies into clinical practice. However, there is little formal training in cancer prevention and early detection. This study describes the effectiveness of a cancer-prevention curriculum called "Recommendations for Cancer Prevention (ReCaP) for Residents" for primary care residency programs. METHODS: The ReCaP for Residents curriculum was organized into eight instructional modules by organ site-specific areas for which there are established primary and secondary cancer-prevention recommendations. The modules include content outlines, learning objectives, slides, and case studies. In-house faculty and 21 residents of two family practice programs participated in an intervention comprising seven one-hour modular presentations during their regular summer teaching program. An established cancer-prevention knowledge test with 100 test items was used to test the residents' knowledge before and after the intervention; the data were analyzed by factor analysis with principal-component extraction and varimax rotation. RESULTS: The residents knew significantly more about cancer prevention after the ReCaP for Residents program. The mean overall prevention knowledge increased significantly (p < .05), and the scores of six of eight specific organ-site areas also increased. CONCLUSION: This study provided evidence that ReCaP for Residents was an effective curriculum for increasing residents' knowledge of cancer prevention. The authors recommend that more extensive programs of this type be implemented.

Curriculum↗

PubMed1995

Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta.

In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have examined the ethnic distribution of this polymorphism using a polymerase chain reaction (PCR)-based genotyping method. Five different ethnic groups were studied: North American Caucasians, African-Americans, Mexican-Americans, Chinese and Koreans. The prevalence of the null genotype was highest among Chinese (64.4%), followed by Koreans (60.2%), African-Americans (21.8%) and Caucasians (20.4%), whereas the prevalence was lowest among Mexican-Americans (9.7%). Interestingly, the prevalence of the deleted genotype in Caucasians differed significantly when 257 individuals drawn from a nation wide organization were compared with 185 people from the New England area (23.7 versus 15.7%, P < 0.05, chi 2 test). These results indicate that there are major differences in the prevalence of this trait attributable to ethnicity and that ethnic origin even among Caucasians should be considered in studies of gene-environment interaction involving this polymorphism.

Asian People↗

PubMed1995

Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype.

A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.

Aged↗

PubMed1995

Strategies for chemoprevention study of premalignancy and second primary tumors in the head and neck.

Recent strides in epidemiology (mutagen sensitivity assays) and basic molecular study of head and neck carcinogenesis are advancing chemoprevention in the head and neck. The clinical preventive activity of retinoids, the most studied and most active chemopreventive agents in this region, has been established in six randomized head and neck trials. Ongoing translational study of the p53 gene, nuclear retinoid receptors, and other cellular and molecular biomarkers will be necessary to achieve continuing progress in head and neck cancer chemoprevention.

Anticarcinogenic Agents↗

PubMed1995

Mutagen sensitivity as a biological marker of lung cancer risk in African Americans.

Cigarette smoking is the major determinant of lung cancer. However, only a fraction of smokers develops lung cancer; genetically determined susceptibility factors seem to play an important role also. Previous case-control studies have shown that in vitro bleomycin-induced mutagen sensitivity is an independent risk factor for head-and-neck cancers, and preliminary data suggest a similar association with lung cancer. However, these studies were almost exclusively performed on Caucasian populations. To test whether ethnic differences in cancer risk are due to differences in mutagen sensitivity, we are using the in vitro mutagen sensitivity assay to conduct a case-control study of mutagen sensitivity and lung cancer risk in low-risk (Mexican-American) and high-risk (African-American) groups. Here we report the results of our ongoing study of 209 African-Americans (90 cases and 119 controls) in the Houston-Galveston area. Mexican-American data will be reported separately as case accrual increases. Predictably, all measures of cigarette smoking status (including intensity, duration, tar content, depth of inhalation, and type of cigarette) were significant predictors of risk. In addition, 55.3% of the cases were mutagen sensitive (defined as > or = 1 break/cell), compared with 24.6% of the controls, with an age-, sex-, and smoking-adjusted odds ratio (OR) of 3.7 (95% confidence limits = 1.4, 9.4). Of interest, higher risks were noted for former smokers (OR = 5.4) compared with current smokers (OR = 3.1) and especially for younger former smokers (< 55 years). By histologic-specific analysis, mutagen sensitivity was significantly associated with risk for adenocarcinoma (OR = 4.8) and squamous cell carcinoma (OR = 8.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1995

A case-control study of wood dust exposure, mutagen sensitivity, and lung cancer risk.

The associations between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust, were assessed in a hospital-based case-control study. There were 113 African -American and 67 Mexican-American cases with newly diagnosed, previously untreated lung cancer and 270 controls, frequency-matched on age, ethnicity, and sex. Mutagen sensitivity ( 1 chromatid break/cell after short-term bleomycin treatment) was associated with statistically significant elevated risk for lung cancer [odds ration (OR) = 4.3; 95% confidence intervals (CI) = 2.3-7.9]. Wood dust exposure was also a significant predictor of risk (overall OR = 3.5; CI = 1.4-8.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was s significant risk factor for African-Americans (OR = 5.5; CI = 1.6-18.9) but not for Mexican-Americans (OR = 2.0; CI = 0.5-8.1). The ORs were 3.8 and 4.8 for non-small cell lung cancer in Mexican-Americans (CI = 1.2-18.5). Stratified analysis suggested evidence of strong interactions between wood dust exposure and both mutagen sensitivity and smoking in lung cancer risk.

Adult↗

PubMed1995

Lung cancer, smoking patterns, and mutagen sensitivity in Mexican-Americans.

BACKGROUND: Mexican-Americans have lower age-adjusted lung cancer incidence rates than non-Hispanic whites and African-Americans. Since 87% of lung cancers are attributed to tobacco exposure, this difference could be explained partly by lower prevalence of cigarette smoking. However, only a fraction of exposed individuals will develop smoking-related cancer, and genetically determined differences in modulation of environmental exposures could also explain some of this ethnic risk differential in lung cancer incidence in the United States. However, little research on genetic susceptibility has been focused on Hispanic populations in the United States. METHODS: We are conducting a case-control study of lung cancer in a high-risk group (African-Americans) and a low-risk group (Mexican-Americans) to evaluate ethnic differences in mutagen sensitivity by an in vitro assay that quantifies mutagen-induced chromosome breaks in short-term lymphocyte cultures. RESULTS: In the 174 Mexican-Americans (67 lung cancer case patients and 107 control subjects) accrued to date, all measures of cigarette smoking (intensity, duration, nicotine and tar contents, depth of inhalation, and type of cigarette) were significant predictors of lung cancer risk. There were significantly higher risks associated with mutagen sensitivity (defined as > or = 1 break/cell) for both former smokers (odds ratio [OR] = 4.5; 95% confidence interval [CI] = 0.9-21.9) and current smokers (OR = 2.6; 95% CI = 0.6-11.1). Mutagen sensitivity also appeared to be implicated in risk in patients who were less than 55 years old at diagnosis (OR = 15.0; 95% CI = 1.0-228.9) and in those with lower cigarette exposure (OR = 11.0; compared with an OR of 1.7 for the heaviest smokers). The overall OR for mutagen sensitivity adjusted for age, sex, and pack-years of smoking was 2.9 (95% CI = 0.8-9.9). Neither current smoking status nor years of exposure shifted the sensitivity profile of case patients and control subjects. CONCLUSION: Although this study showed higher percentages of nonsmokers among Mexican-Americans than our previously reported data for African-Americans, the Mexican-American case patients were heavier smokers than the African-American case patients. The prevalence of mutagen sensitivity for Mexican-Americans was 64.1% in case patients and 26.2% in control subjects. In African-Americans, mutagen sensitivity was previously reported to be 55.3% in case patients and 24.6% in control subjects. These preliminary data do not support our a priori hypothesis that a lower prevalence of mutagen sensitivity in Mexican-Americans would account for the lower incidence of lung cancer. Mutagen sensitivity, however, is only one of an array of potential susceptibility markers that we are evaluating in this unique population.

Black or African American↗

PubMed1994

Mutagen sensitivity as a risk factor for second malignant tumors following malignancies of the upper aerodigestive tract.

BACKGROUND: Second malignant tumors in patients successfully treated for an initial cancer of the upper aerodigestive tract are an important cause of morbidity and mortality. Biologic markers capable of identifying high-risk subgroups of patients who could be targeted for intensive clinical surveillance, therefore, have immense therapeutic and prognostic relevance. We previously demonstrated in a pilot study of 84 patients with cancers of the upper aerodigestive tract that mutagen sensitivity was a significant predictor of risk of developing second malignant tumors. PURPOSE: We extended the study to include 278 patients diagnosed with previously untreated cancers of the upper aerodigestive tract from 1987 to August 1993. METHODS: For each patient, base-line (pretreatment) mutagen sensitivity was measured in vitro in 50 metaphases established from peripheral lymphocyte cultures. Patients with an average of more than 1 chromosomal break/cell were deemed mutagen hypersensitive. Cox proportional hazards analysis was used to predict the risk of developing second malignant tumors associated with mutagen sensitivity. RESULTS: Overall, 44% of the case group exhibited mutagen hypersensitivity. There were no differences in the distribution of mutagen hypersensitivity by site, sex, stage of disease, or smoking status. There were 17 synchronous and 11 metachronous cancers, of which 15 (54%) were smoking-related malignancies. Sixteen (13.1%) of the mutagen-sensitive patients developed second malignant tumors, compared with 12 (7.7%) of the nonsensitive patients. The mean break/cell value (+/- SD) for patients developing second malignant tumors was 1.17 (+/- 0.54), compared with 0.98 (+/- 0.44) for patients with only one cancer (P = .04). Mutagen hypersensitivity conferred a relative risk of 2.67 (95% confidence interval = 1.22-5.79) of developing second malignant tumors. CONCLUSIONS: Mutagen hypersensitivity increases the risk of developing second malignant tumors. IMPLICATIONS: Future research should focus on the molecular mechanisms underlying mutagen sensitivity.

Adult↗