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T C Hsu

Publications and source records attributed to T C Hsu.

At least 73 records · Page 4Linked to original sources
PubMed1997

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.

Adult↗
PubMed1997

The efficacy of intrathecal coadministration of morphine and bupivacaine for labor analgesia.

BACKGROUND: Intrathecal (i.t.) opioids can provide labor analgesia, but the onset of pain relief is slow. Bupivacaine has the beneficial property of less motor blockade than other local anesthetics. This study retrospectively examined the efficacy of concomitant use of i.t. morphine and bupivacaine for labor pain relief. METHODS: Fifty five nulliparas who requested analgesia in the active phase (IA group) prior to a cervical dilation 3.9 +/- 0.6 cm and received i.t. morphine 0.5 mg and 0.1% bupivacaine 2.5 mg served as the treatment group, and 88 similar nulliparas who did not request and receive analgesia served as the control group. RESULTS: The mean onset time of analgesia was 2.6 +/- 0.5 min, the duration was 4-12 h and 93% of parturients did not request additional analgesia after a single injection of i.t. morphine and bupivacaine. The active phase of the first and second stages of labor in the treatment group were significantly longer [318 +/- 214 min vs. 176 +/- 120 min; 74 +/- 29 min vs. 37 +/- 26 min]. Frequency of instrument-assisted vaginal delivery was higher compared with the control group (30.9% vs. 14.1%). However, there were no significant differences in the rate of cesarean section and the Apgar scores of newborns at 1 min and 5 min between the treatment and control group. The major side effects of the treatment group included pruritus (48%), nausea (40%), vomiting (37%), somnolence (27%), shivering (27%), urinary retention (21%), hypotension (15%), and bradycardia (13%). Most of the side effects were mild and could be alleviated by naloxone. Neither post-spinal headache nor respiratory depression was noted. CONCLUSIONS: Our results showed that a single injection of i.t. morphine and bupivacaine provided rapid onset and effective analgesia with manageable side effects and without major complications. Thus, i.t. morphine and bupivacaine provides an alternative to epidural analgesia for most women in labor.

Adult↗
PubMed1996

Genetic susceptibility to head and neck squamous cell carcinoma.

BACKGROUND: In addition to influences of exposure to carcinogenic compounds, the development of cancer may depend on an individual intrinsic cancer susceptibility. Biomarkers for cancer susceptibility can be powerful additions to epidemiologic analyses. PURPOSE: This multicenter, case-control analysis combines previously published data and new data to substantiate the value of mutagen sensitivity as a biomarker of susceptibility to head and neck squamous cell carcinoma and, more importantly, to gain insight into the interaction between susceptibility and exposure to carcinogens. METHODS: Mutagen sensitivity (mean number of chromatid breaks per cell of cultured lymphocytes treated with bleomycin in the late S-G2 phase of the cell cycle) was determined in 313 patients with head and neck cancer and in 334 control subjects at two major U.S. medical institutions and one European institution, yielding a unique study population. The ages of the case and control subjects, as well as their history of use of tobacco and alcohol, were also recorded. The relationships between variables were analyzed by use of Student's t tests, Spearman's rank correlations, and multiple linear regression. For estimation of cancer risk, crude odds rations (ORs) were measured and multiple logistic regression was performed. All P values were based on two-sided tests. RESULTS: There were no differences across institutions in the distribution of mutagen sensitivity (Kruskal-Wallis test) for both case subjects and control subjects. Values for case subjects were consistently and significantly (P<.0001) higher than values for control subjects in the overall analyses. Age and tobacco or alcohol use did not influence the outcome in terms of mutagen-sensitivity values for either the case or the control subjects. A mean number of breaks per cell dichotomized at 1.0 was found to be the best predictor of a hypersensitive phenotype. For nonsensitive, heavy smokers, the OR was 11.5 (95% confidence interval [CI] = 5.0-26.6). This risk increased dramatically in mutagen-hypersensitive, heavy smokers to 44.5 (95% CI = 17.4-114.0). Multiple logistic regression analysis confirmed these results, and a significant trend was found (P<.01) for the dose-dependent increase in cancer risk by smoking. The consumption of alcohol potentiated the effects of smoking, resulting in an OR of 57.5 (95% CI = 17.5-188.0) in hypersensitive persons. CONCLUSIONS: Mutagen sensitivity was found to be a biomarker of cancer susceptibility. This study underscores the importance of utilizing both susceptibility markers and the exposure data for the identification of persons at high risk of developing cancer. IMPLICATIONS: More accurate risk estimation can define susceptible subgroups who might be targeted for intensive behavioral interventions, surveillance through screening, and enrollment in chemoprevention programs.

Adult↗
PubMed1996

Mutagen sensitivity in humans. A comparison between two nomenclature systems for recording chromatid breaks.

Currently, there are two systems in use for recording chromatid breaks, either spontaneously occurring or induced by mutagens: The International System for Human Cytogenetic Nomenclature (ISCN) and the Chatham Barrs Inn Conference (CBIC) recommendation. The former system considers that a chromatid break is recognized only when the chromatid fragment is displaced to the other side of its sister chromatid, while all others, regardless of the distance between the two broken ends, are called chromatid gaps. The CBIC system recognizes a chromatid break when the intervening achromatic segment is longer than or equal to the diameter of the chromatid, whether the fragment is displaced or not. Minor lesions are called chromatid gaps. We conducted experiments using bleomycin treatment of human cells (primary cultures or lymphoblastoid cell lines) and read the chromatid lesions both ways. We conclude that the CBIC system appears to have more direct biologic relevance than the ISCN system.

Bleomycin↗
PubMed1996

Quality of life and life satisfaction in families after a child has undergone corpus callostomy.

Epilepsy is a chronic neurological condition which can have a detrimen tal effect on patients' quality of life (QOL). We evaluated the overall satisfaction with QOL and changes in QOL in 25 families with children who had undergone corpus callostomy for severe epilepsy. The mean age of seizure onset was 3.4 years, and the mean period from seizure onset to operation was 5.2 years. Mean follow-up was 19.3 months. Twenty of 22 patients had various degrees of mental retardation. Mean reduction in severity of seizure activity was 64%. Nineteen of 25 (76%) parents were satisfied with the surgical result. Eighteen of 25 parents (72%) described a good level of satisfaction with their families QOL after callostomy. Reduction in severity of seizure activity was significantly correlated with how successful families considered the surgery to be and how satisfied they were with their QOL (r = 0.72 and 0.77, respectively). Life domains showing one greatest improvement after callostomy included level of self-care, family life, and school performance. Improvements in level of self-care, family life, and school performance were associated with higher levels of life satisfaction (r = 0.69, 0.60, and 0.59, respectively). Hyperactivity, attention span, and social skills improved significantly in 11 patients after surgery. Callostomy did not improve mental performance. We conclude that improved seizure control after callostomy is also associated with improved QOL.

Achievement↗
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

SS-A/Ro antibodies in Chinese patients with systemic lupus erythematosus and Sjögren's syndrome.

Serum from 53 patients with systemic lupus erythematosus (SLE) and 23 patients with primary Sjögren's syndrome (SS) were studied for anti-52-kDa SS-A/Ro, anti-60-kDa SS-A/Ro, and anti-SS-B/La antibodies by immunoblotting and enzyme-linked immunosorbent assay (ELISA). By immunoblotting, anti-SS-A/Ro was detected in 16 (30%) patients with SLE and 17 (74%) patients with SS. Anti-SS-B/La was detected in 22 (41%) patients with SLE and 15 (65%) patients with SS. Serum from 14 of the 16 SLE patients with anti-SS-A/Ro reacted with the 60-kDa protein and 15 serum samples from these patients recognized the 52-kDa protein. Serum with anti-60-kDa SS-A/Ro alone was not found. Serum from all of the 17 SS patients with anti-SS-A/Ro reacted with the 52-kDa protein, whereas serum from only two of these patients recognized the 60-kDa protein. By ELISA, the frequency of anti-SS-A/Ro (antibodies to the 60-kDa and/or 52-kDa of SS-A/Ro proteins) in patients with SLE and SS was 43/53 (81%) and 15/23 (65%), respectively. Anti-48-kDa SS-B/La was found in 28% and 48% of SLE and SS patients, respectively. Serum from 77% of SLE patients and 48% of SS patients reacted with the 60-kDa SS-A/Ro protein. Serum from 45% of SLE patients and 52% of SS patients reacted with the 52-kDa SS-A/Ro protein. Patients with SLE had significantly higher titers of antibodies to 60-kDa SS-A/Ro compared with patients with SS. Anti-SS-A/Ro and anti-SS-B/La are common in both SLE and SS. The different reactivities of anti-52-kDa and anti-60-kDa antibodies in serum from patients with SLE and SS may represent differences in conformation-dependent epitopes of SS-A/Ro autoantigens.

Adult↗
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

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

Modulator inhibits nuclear translocation of the glucocorticoid receptor and inhibits glucocorticoid-induced apoptosis in the human leukemic cell line CEM C-7.

Modulator is an endogenous low-molecular-weight regulator of both glucocorticoid and mineralocorticoid receptors as well as protein kinase C. Structural analysis of modulator purified to apparent homogeneity suggests that it is a novel ether aminophosphoglyceride. In this report, we show that modulator inhibits cytosolic human glucocorticoid receptor (GR) complex activation as measured by DNA-cellulose binding. In addition, modulator blocks glucocorticoid-induced nuclear translocation of the GR in intact human leukemic (CEM C-7) cells, as illustrated by immunocytochemical localization. Furthermore, we demonstrate that modulator, by blocking the activation and subsequent translocation of GR, inhibits glucocorticoid-mediated apoptosis, characterized by chromatin condensation, internucleosomal DNA fragmentation, and cell death in glucocorticoid-sensitive CEM C-7 cells. Modulator inhibits glucocorticoid-induced c-myc gene repression and glucocorticoid receptor gene up-regulation. These data suggest that modulator functions to regulate the GR in intact cells as well as in cytosolic preparations. In addition, the inhibition of glucocorticoid-induced programmed cell death by modulator sheds light on the cellular function of modulator as well as on the mechanism by which apoptosis occurs in CEM C-7 cells.

Amino Acid Sequence↗
PubMed1995

Neuromuscular injury during limb lengthening: a longitudinal follow-up by rabbit tibial model.

Limb lengthening has been used for many years to correct congenital anomalies and unequal leg length. Some surgeons focus on bone genesis and anatomical alignment, and pay less attention to potential damage to muscles, nerves, and vessels during the gradual stretching. In an attempt to identify the presence and extent of neuromuscular abnormalities during leg elongation, a rabbit tibial osteotomy model was used for 17 male rabbits, and fixation-distraction apparatuses were applied at a rate of 1 mm lengthening per day. Electrophysiological test was used to investigate both hindlegs every 2 weeks for 8 weeks after surgery. Needle electromyography (EMG) showed denervation in the elongated legs with 14 limbs having peroneal nerve damage and 12 limbs having damage to the posterior tibial nerve. Nerve regeneration signs were found in ankle extensors and flexors beginning 2 weeks postoperatively. The results of nerve conduction studies revealed significant differences (P < .05) in CMAP amplitude (mV) and area (mV.mS) in ankle extensors and flexors between elongated and nonelongated legs. There was no significant side-to-side difference with respect to distal latency. The incidence of neuromuscular injury was common in these rabbits. These findings suggest that early detection of neuromuscular involvement by electrophysiological test is a practical way to assess neuromuscular function during limb lengthening.

Animals↗
PubMed1995

Impact of decreased serum transaminase levels on the evaluation of viral hepatitis in hemodialysis patients.

The value of serum transaminases (ST) in evaluating hepatitis B (HBV) and C (HCV) infection was studied in 217 hemodialysis (HD) patients and 804 normal controls. Mean serum aspartate aminotransferase (AST) was 22.3 (22.0-22.7) and 22.6 (21.6-23.6) IU/l or 0.371 (0.366-0.378) and 0.376 (0.36-0.393) mu kat/l in controls and HD patients, respectively (nonsignificant), while mean serum alanine aminotransferase (ALT) was 20.3 (19.9-20.7) and 16.3 (15.3-17.3) IU/l or 0.338 (0.331-0.345) and 0.271 (0.255-0.288) mu kat/l in these two groups (p < 0.001). However, both AST and ALT became significantly depressed in HD patients after adjusting for age, gender, HBV surface antigen (HBsAg) and anti-HCV. The usual practice of regarding AST and ALT as being 'abnormal' in evaluating viral hepatitis when they exceeded the upper reference range (40 and 46 IU/l or 0.666 and 0.766 mu kat/l in our laboratory) was then critically assessed by the receiver operating characteristic (ROC) curve. ROC analysis showed that ST was useless in detecting HBsAg, while the best cutoff point for detecting the presence of anti-HCV was 18 IU/l (0.3 mu kat/l) for AST and 16 IU/l (0.266 mu kat/l) for ALT in HD patients, respectively. These are considerably lower than the conventional criteria for an 'abnormal' ST. We conclude that ST are decreased in HD patients and that the cutoff value of ST for detecting HCV should be set at lower levels to enhance their diagnostic yield.

Alanine Transaminase↗
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↗