A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls

Wu, Xifeng; Gu, Jun; Amos, Christopher I.; Jiang, Hong; Hong, Waun Ki; Spitz, Margaret R.

doi:10.1002/(sici)1097-0142(19980915)83:6<1118::aid-cncr10>3.3.co;2-1

Cited by 17 publications

(23 citation statements)

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“…Our results corroborate previous findings of mutagen sensitivity as a predisposition factor forLC [13][14][15]23,24 and also suggest a substantial interplay between mutagen sensitivity and other established LC risk factors in modulating risk.…”

Section: Discussionsupporting

confidence: 92%

“…As previously described, 24 2 parallel blood cultures were set up when the blood was received. For the BPDE assay, on the 3rd day of incubation, the cultures were treated with 2 lM BPDE for 24 hr.…”

Section: Mutagen Sensitivity Assaymentioning

confidence: 99%

“…The mutagen sensitivity phenotype has been shown to increase risks of upper aerodigestive tract cancer, 17,18 head and neck cancer, [19][20][21] oral premalignant lesions 22 and LC. [13][14][15]23,24 To date, there have been few studies that have comprehensively evaluated the association between LC risk in the context of multiple risk factors, including markers of genetic susceptibility and a panel of epidemiological risk factors. The interplay between genetic susceptibility and potential epidemiological covariates in predicting LC risk has not yet been addressed.…”

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confidence: 99%

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Interplay between mutagen sensitivity and epidemiological factors in modulatinglung cancer risk

Lin

Etzel

et al. 2007

Intl Journal of Cancer

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Few studies have assessed mutagen sensitivity and lung cancer (LC) risk associations in the context of multiple epidemiological risk factors. We evaluated mutagen sensitivity as a susceptibility marker and explored the interplay of the genetic marker and multiple epidemiologic risk factors in modulating LC risk. This largest case-control study included 977 newly diagnosed LC patients and 977 controls, matched by age, gender, ethnicity and smoking status. Cases exhibited significantly higher mutagen sensitivity than controls in bleomycin (0.76 vs. 0.62 breaks/cell, p < 0.001) and benzo[a]pyrene diol epoxide (BDPE) assays (0.70 vs. 0.61 breaks/cell, p < 0.001). Mutagen sensitivity also exhibited doseresponse relationship with LC risk in quartile analysis (p for trend <0.001). In smokers, history of emphysema, absence of hay fever history, LC in first-degree relatives, belomycin sensitivity, and high pack-year were identified to be the top 5 significant risk factors in a stepwise logistic regression model (odds ratios (ORs) of 2.69, 1.91, 1.84, 1.73 and 1.67, respectively). Analyses of joint effects of risk factors showed that compared to the reference group, subjects with no exposure to any of the aforementioned risk factors, the ORs for exposure to 1, 2, 3, 4, 5 or more of the risk factors were 1.56, 2.39, 3.75, 6.74 and 17.39, respectively (p for trend <0.001). This study strongly supports mutagen sensitivity as a predisposition factor for LC and demonstrates the importance of assessing multiple risk factors to comprehensively assess LC risk. This new integrative approach should facilitate identification of high-risk subgroups and has important implications in LC prevention. ' 2007 Wiley-Liss, Inc.Key words: mutagen sensitivity; epidemiologic risk factors; lung cancer risk Lung cancer (LC) is the leading cause of cancer-related death in the United States, 1 although it is estimated that >80% of LC can be attributed to cigarette smoking, 2 a variety of other exposures also contribute to LC risk, including occupational exposure to asbestos, dusts (wood dust, metal, concrete, fiberglass, etc.), polycyclic hydrocarbons, inorganic arsenic, diesel, exhaust, fumes. 3 Previous studies have also suggested a link between family history of LC and the risk of smoking-related cancer and LC among firstdegree relatives. [4][5][6] Chronic respiratory diseases such as emphysema, hay fever, pneumonia, asthma and bronchitis have all been implicated in modifying LC risk. [7][8][9] In never smokers, exposure to environmental tobacco smoke, or second-hand smoke, has been shown to confer increased risk of LC. 10,11 The fact that only a small fraction of smokers develops LC suggests that host susceptibility may be involved in LC risk. [12][13][14][15] Host susceptibility, such as interindividual variation in DNA repair capacity to environmental carcinogens found in tobacco smoke, may predispose susceptible individuals to increased risk of LC. Hsu et al. 16 developed a mutagen sensitivity assay that quantifies the frequency of chromati...

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Section: Discussionsupporting

confidence: 92%

Section: Mutagen Sensitivity Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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Interplay between mutagen sensitivity and epidemiological factors in modulatinglung cancer risk

Lin

Etzel

et al. 2007

Intl Journal of Cancer

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“…A series of studies has indicated that mutagen sensitivity is a promising environmental-related cancer risk predictor (Hagmar et al, 1994;Bonassi et al, 1995). This assay has been successfully expanded by replacing the initial test mutagen bleomycin with 4-nitroquinoline-1-oxide (an UV mimetic agent), g-radiation, and BPDE to measure risk of different cancers (Miller et al, 1998;Wu et al, 1998b;Zhao et al, 2001). By using a mutagen to induce a specific type of DNA damage, detailed information can be acquired about host susceptibility with regard to a given DNA repair pathway.…”

Section: Dna Damage and Repairmentioning

confidence: 99%

Genetic susceptibility to tobacco-related cancer

et al. 2004

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Although cigarette smoking is the dominant risk factor for several epithelial cancers, only a small fraction of individuals with tobacco exposure develop cancer. The underlying hypothesis is that genetic factors may render certain smokers more susceptible to cancer than others. Genetic alterations in critical regulatory pathways may predispose cells to carcinogenesis. These pathways include regulation of xenobiotic metabolism; control of genomic stability, including DNA repair mechanisms, cell-cycle checkpoints, apoptosis and telomere length; and control of microenvironmental factors, such as matrix metalloproteinases, inflammation and growth factors. In addition, epigenetic events, such as promoter hypermethylation and loss of imprinting, are also involved in carcinogenesis. In this review, we will summarize recent advances in genetic susceptibility to tobacco-related cancer. Emphasizing on risk assessment, we will describe how genetic variations in the above-mentioned genetic pathways modify the tobacco-related cancer risk. In addition, we will discuss how genetic variations may assist in predicting clinical outcome, such as the natural history of cancer and treatment response. The measurements of genetic susceptibility by both genotypic and phenotypic assays are covered in the text. Finally, we present a number of current concerns that need to be addressed as the exciting field of molecular cancer epidemiology advances rapidly.

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“…Given the significant role of carcinogen exposure in these tumours, it proves difficult to study host factors related to cancer risk (Proia et al, 2006). Such studies are based on measurement of host DNA repair capacity, such as the bleomycin chromosome breakage assay (Wu et al, 1998;Rajaee-Behbahani et al, 2001), the host-cell reactivation assay (Diem and Runger, 1997), or the comet assay (Kleinsasser et al, 2000). These assays suggest host impairments in DNA repair, but they have found limited application in the clinical setting because they require intact cells, are labour intensive and may have limitations with respect to reproducibility (Berwick and Vineis, 2000).…”

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Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Slebos

Vadivelu

et al. 2008

Br J Cancer

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Carcinogen exposure from tobacco smoking is the major cause of upper aerodigestive tract cancer, yet heavy smokers only have about a 10% life-time risk of developing one of these cancers. Current technologies allow only limited prediction of cancer risk and there are no approved screening methods applicable to the general population. We developed a method to assess somatic mutational load using small-pool PCR (SP-PCR) and analysed mutations in DNA isolated from cells obtained by mouth rinse. Mutation levels in the hypermutable tetranucleotide marker D7S1482 were analysed in specimens from 25 head and neck squamous carcinoma (HNSCC) cases and 31 controls and tested for associations with age, smoking history and cancer status. We found a significant association between mutation frequency and age (P ¼ 0.021, Generalized Linear Model (GLM), N ¼ 56), but no influence of smoking history. Cases had higher mutation frequencies than controls when corrected for the effects of age, a difference that was statistically significant in the subgroup of 10 HNSCC patients who were treated with surgery only (P ¼ 0.017, GLM, N ¼ 41). We also present evidence that cancer status is linked to levels of nonunique, and presumably clonally derived, mutations in D7S1482. Insertion mutations were observed in 833 (79%) of 1058 alleles, of which 457 (43%) could be explained by insertion of a single repeat unit; deletion mutations were found in 225 (21%) of tested alleles.In conclusion, we demonstrate that the sensitive detection of single molecule mutations in clinical specimens is feasible by SP-PCR. Our study confirms an earlier report that microsatellite mutations increase with age and is the first to provide evidence that these mutations may be associated with cancer status in individual subjects.

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A parallel study of in vitro sensitivity to benzo[a]pyrene diol epoxide and bleomycin in lung carcinoma cases and controls

Cited by 17 publications

References 1 publication

Interplay between mutagen sensitivity and epidemiological factors in modulatinglung cancer risk

Interplay between mutagen sensitivity and epidemiological factors in modulatinglung cancer risk

Genetic susceptibility to tobacco-related cancer

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

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