Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

Conforti-Froes, Nívea; El‐Zein, Randa; Abdel‐Rahman, Sherif Z.; Zwischenberger, Joseph B.; Au, William W.

doi:10.1016/s0027-5107(97)00106-1

Cited by 39 publications

(24 citation statements)

References 25 publications

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“…Samples were collected in the afternoon for personal delivery via commercial airlines to our laboratory in Galveston, Texas We used the procedure for the tandemprobe FISH assay described by Rupa et al (17), which we previously used successfully (19). We used fluorescence microscopy to analyze 1,500 interphase nuclei/donor for the presence of chromosome aberrations.…”

Section: Methodsmentioning

confidence: 99%

“…The population size for our study is adequate for a cytogenetic analysis (29,30). Although the population size is small for genotype analysis in a molecular epidemiologic investigation, we expected that the combination of genotype analysis and cytogenetic study would provide some insight into the genetic susceptibility to pesticides, as we -have noticed previously in cigarette smokers (19). Furthermore, the extensive pesticide exposure conditions for the farmers may increase our chance of detecting an association between genetic susceptibility and biological effects.…”

mentioning

confidence: 87%

“…Therefore, some of these highly relevant cytogenetic assays were used in our study. Specifically, we conducted the standard chromosome aberration assay, the challenge assay to determine abnormal DNA repair response (18), and the tandem-probe FISH assay (17,19) (22)(23)(24).…”

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confidence: 99%

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Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.

Sierra‐Torres

Cajas-Salazar

et al. 1999

Environ Health Perspect

100

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Exposure to pesticides remains a major environmenal health problem. Health risk from such exposure needs to be more precisely understood. We conducted three different cytogenetic assays to elucidate the biological effects of exposure to mixed pesticides in 20 Costa Rica farnMrs (all nonsmokers) compared with 20 matched controls. The farmers were also exposed to dibromochloropropane during the early employment years, and most of them experienced sterility/fertility problems. Our data show that the famers had consistently higher frequencies of chromosome aberrations, as determined by the standard chromosome aberration assay, and significandy abnormal DNA repair responses (p c 0.05), as determined by the challenge assay, but no statistically significant differences in the tandem-probe fluorescence in situ hybridization (FISH) assay (p > 0.05). Genotype analysis indicates that farmers with certain "unfavorable" versions of polymorphic metabolizing genes (cytochrome P4502El, the glutathione S-transferases mu and theta, and the paraoxonase genes) had significantly more biological effects, as determined by all three cytogenetic assays, than both the farmers with the "favorable" alleles and the matched controls. A unique observation is that, in individuals who had inherited any of the mentioned "unfavorable" alleles, farmers were consistentdy underrepresented. In condusion, the Costa Rican farmers were exposed to genotoxic agents, most likely pesticides, which expressed the induction of biological and adverse health effects. The farmers who had inherited "unfavorable" metabolizing alleles were more susceptible to genotoxic effects than those with "favorable" alleles. Our genotype data suggest that the well-recognized "healthy worker effect" may be influenced by unrecognized occupational selection pressure against genetically susceptible individuals.

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Section: Methodsmentioning

confidence: 99%

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confidence: 87%

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Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.

Sierra‐Torres

Cajas-Salazar

et al. 1999

Environ Health Perspect

100

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“…12,13 Several single nucleotide polymorphisms, including an adenine (A) to cytosine (C) (A 3 C) transition, which leads to Lys751Gln in exon 23 of the XPD gene, have been shown to be associated with elevated frequency of chromosomal aberrations and a variety of environmentally induced cancers in adults. [14][15][16][17] There is also evidence that dysregulation of DNA repair proteins and NER pathways may be involved in pathogenesis and prognosis of some myeloid leukemia.…”

Section: Introductionmentioning

confidence: 99%

XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report

Mehta

Alonzo

Gerbing

et al. 2006

Blood

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Genetic polymorphisms result in interindividual variation in DNA repair capacity and may, in part, account for susceptibility of a cell to genotoxic agents and to malignancy. Polymorphisms in XPD, a member of the nucleotide excision repair pathway, have been associated with development of treatment-related acute myeloid leukemia (AML) and with poor outcome of AML in elderly patients. We hypothesized that XPD Lys751Gln polymorphism may play a role in causation of AML in children and, as shown in adults, may affect the outcome of childhood AML therapy. Genotyping of 456 children treated for de novo AML was performed at XPD exon 23. Genotype frequencies in patients were compared with healthy control subject frequencies, and patient outcomes were analyzed according to genotype. Gene frequencies in AML patients and healthy controls were similar. There were no significant differences in overall survival (P ‫؍‬ .82), eventfree survival (P ‫؍‬ .78), treatment-related mortality (P ‫؍‬ .43

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“…Second, both chromosomes have been suggested as playing a role in the development of prostate cancer (6)(7)(8)(9)(10). Third, previous studies with human lymphocytes have shown an elevated frequency of breakage in the heterochromatin regions at 1q and 9q after exposure to a variety of environmental clastogens, such as benzene, ionizing radiation, and pesticides (17)(18)(19). In addition, breaks affecting the centromeric and pericentromeric heterochromatin regions of human chromosomes could lead to mutations, chromosomal rearrangements, and increased genomic instability (20,21).…”

Section: Introductionmentioning

confidence: 99%

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

El‐Zein

Sierra

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Prostate cancer is an extremely complex disease, and it is likely that chromosomal instability is involved in the genetic mechanism of tumorigenesis. Several chromosomes have been labeled as “players” in the development of prostate cancer, among them chromosome 1 and X chromosome have been reported to harbor prostate cancer susceptibility loci. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures from 126 study subjects, 61 prostate cancer patients, and 65 healthy controls. We evaluated chromosomal instability using a fluorescence in situ hybridization assay using two probes targeting specific regions on X chromosome and chromosome 1. Our results showed a significantly higher mean level of spontaneous breaks involving the X chromosome in patients compared with controls (mean ± SE, 2.41 ± 0.26 and 0.62 ± 0.08, respectively; P < 0.001). Similarly, chromosome 1 spontaneous breaks were significantly higher among cases compared with controls (mean ± SE, 1.95 ± 0.24 and 1.09 ± 0.16, respectively; P < 0.001). Using the median number of breaks in the controls as the cutoff value, we observed an odds ratio (95% confidence interval) of 15.53 (5.74 - 42.03; P < 0.001) for spontaneous X chromosome breaks and 3.71 (1.60 - 8.63; P < 0.001) for chromosome 1 breaks and risk of development of prostate cancer. In conclusion, our preliminary results show that spontaneous chromosome instability could be a risk factor for prostate cancer.

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Predisposing genes and increased chromosome aberrations in lung cancer cigarette smokers

Cited by 39 publications

References 25 publications

Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.

Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.

XPD Lys751Gln polymorphism in the etiology and outcome of childhood acute myeloid leukemia: a Children's Oncology Group report

Chromosomal Instability in Peripheral Blood Lymphocytes and Risk of Prostate Cancer

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