Environmental Tobacco Smoke, Genetic Susceptibility, and Risk of Lung Cancer in Never-Smoking Women

Bennett, William P.; Alavanja, Michael C.R.; Blömeke, Brunhilde; Vähäkangas, Kirsi; Castrén, Katariina; Welsh, Judith A.; Bowman, Elise D.; Khan, Mohammed A.; Flieder, Douglas B.; Harris, Curtis C.

doi:10.1093/jnci/91.23.2009

Cited by 164 publications

(101 citation statements)

References 39 publications

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“…In addition, Hecht et al 13 have measured urinary metabolites of the tobacco-specific carcinogen NNK and have found that never smokers exposed to ETS have 2-5% levels of active smokers, a higher level than expected on the basis of the exposure level. Bennett et al 14 have found that, when compared to never smokers who had no ETS exposure, never smokers with exposure to ETS who developed lung cancer were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) (odds ratio ϭ 2.6; 95% confidence interval 1.1-6.1). Therefore, it is not unreasonable to hypothesize that the observed relative risks in lifetime nonsmokers exposed to ETS are due to a subpopulation of more susceptible individuals.…”

Section: Discussionmentioning

confidence: 99%

Dose‐response relationship in tobacco‐related cancers of bladder and lung: A biochemical interpretation

Víneis

Alavanja

Garte

2003

Intl Journal of Cancer

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The purpose of our study is to address the challenge of evaluating carcinogenic effects at low levels of exposure to carcinogens. We examine the shape of the dose-response relationship between tobacco smoking and cancers of the bladder and lung, and the implications for the evaluation of the effects of exposure at lower levels, for example, environmental tobacco smoke (ETS). DOSE-RESPONSE RELATIONSHIPS IN TOBACCO CARCINOGENESIS: BLADDER AND LUNG CANCERThe fact that low doses of tobacco may have a carcinogenic effect proportionally greater than high doses is suggested by the study of dose-response relationships. A previous study, based on the re-analysis of a multicenter case-control study on lung cancer and of several studies on bladder cancer, 1 suggested that the dose-response relationship between cigarette smoking and cancer risk tends to level off after a dose of approximately 20 -25 cigarettes/day. A few explanations were put forward to explain leveling off, including bias (less accurate reporting by heavy smokers with cancer), lower inhalation at high doses or genetic heterogeneity of the population, with a "depletion of susceptibles" at low-dose levels. To test the latter hypothesis, we have reviewed the recent studies on smoking and bladder cancer, a type of tumour that is particularly well studied from a biochemical-molecular point of view (Tables I and II).We have identified all the cohort or case-control studies on smoking and bladder cancer published from 1985 to 2002 (those published before were reviewed in the IARC Monograph on tobacco smoking 2 ). We have considered men only because data for women tended to be unstable. We have extracted dose-response data, showing odds ratios and 95% confidence intervals whenever possible. Table I shows the results of case-control studies, and Table II those of cohort studies. Virtually all studies, except 1 case-control (Momas et al., 1994) and 2 cohort studies (Engeland et al., 1996;Tulinius et al., 1997), show a leveling off after 20 -30 cigarettes/day. Engeland et al. (1996) and Tulinius et al. (1997) show an attenuation of the slope but not a clear leveling off. The consistency between the 2 different designs suggests that we are observing a real phenomenon and not an artifact because different types of bias occur in case-control and in cohort investigations. In fact, only the former design is prone to retrospective recall bias, with underestimation of heavy consumption by cancer cases.There are other examples in the literature in which the shape of the dose-response relationship levels off. The relationship between TCDD (dioxin) exposure (measured in the plasma of the exposed workers) and total mortality from cancer 3 shows a plateauing of the curve, i.e., an effect that is proportionally greater at lower levels of exposure. Other examples are liver tumours and vinyl chloride in rats 4 or lung cancer and arsenic in humans. 5 However, it should be noted that these are heterogeneous situations, concerning both mutagens like vinyl chloride and chemicals like...

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Section: Discussionmentioning

confidence: 99%

Dose‐response relationship in tobacco‐related cancers of bladder and lung: A biochemical interpretation

Víneis

Alavanja

Garte

2003

Intl Journal of Cancer

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“…However, findings reported by Georgiadis et al (2004) indicate that nonsmoking students exposed to urban air pollution and ETS with GSTM1 deletion had higher levels of DNA adducts in their lymphocytes compared with GSTM1 ''wild-type'' participants. Never-smoking women with GSTM1 null had statistically significant greater risk of developing lung cancer from exposure to ETS (Bennett et al, 1999). Lung cancer risk in GSTM1-null individuals exposed to indoor coal combustion emissions was elevated compared with individuals with an active copy of GSTM1.…”

Section: Introductionmentioning

confidence: 90%

Biomarkers of exposure to combustion by-products in a human population in Shanxi, China

Naufal

Zhu

et al. 2009

J Expo Sci Environ Epidemiol

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Emissions of complex mixtures of polycyclic aromatic hydrocarbons (PAHs) and other compounds into the environment represent a potential threat to the health of humans. Information regarding the dose and duration of exposure is essential to determine the degree of risk and to identify sensitive receptors within a population. Although measurements of chemical concentrations in air may be used to estimate exposures, internal biomarkers provide more accurate information regarding the dose of exposure and retention of toxic chemicals. This study was conducted in a population in rural China exposed to PAHs from a variety of sources. The study population was located in an area known to have an elevated incidence of birth defects. Parents of children born with a neural tube defect (NTD) were recruited as case participants and parents of children born with no visible birth defect were recruited as controls. The study was designed to test the hypothesis that parents of children born with a NTD would exhibit a biomarker of exposure at higher levels than the parents of a child with no visible birth defect. A total of 35 mothers and 32 fathers were recruited as case participants, and 18 mothers and 19 fathers were recruited as control participants. Venous blood was collected from the study participants by hospital staff as soon as possible following the birth of the child. PAHs were isolated from the whole blood by solvent extraction and DNA was isolated from a separate aliquot of blood for 32 Ppostlabeling to measure bulky adducts. Single Nucleotide Polymorphisms (SNPs) in phase II enzymes were also monitored in an attempt to identify sensitive receptors. Both total and carcinogenic PAH (cPAH) concentrations were elevated in the parents of case children. Both values were elevated significantly in mothers, whereas only cPAH concentrations were elevated significantly in fathers. Levels of DNA adducts were highly variable and displayed a reverse pattern to that of PAH levels in blood. None of the polymorphisms evaluated were correlated with PAH levels or DNA adducts. For mothers, whose total PAH concentration was above the median concentration, the age-adjusted odds ratio (OR) for having a child with a NTD was 8.7. Although this suggests that PAHs may be a contributing factor to the risk of NTDs, the lack of a correlation with DNA adducts would suggest a possible non-genotoxic mechanism. Alternatively, the PAHs may be a surrogate for a different exposure that is more directly related to the birth defects. The results have shown that blood levels of PAHs may be used to identify populations exposed to elevated concentrations of combustion by-products.

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“…Other mechanisms that have been reported to play a role in determining the carcinogenic potential are alterations in the detoxification of carcinogenic compounds, which are mediated by the conjugation of the compounds or their metabolites to glutathione by glutathione S-transferase (GST). GSTs are class II detoxification enzymes that are encoded by four classes of polymorphic genes [Bennett et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens

Russo

Tahin

Lareef

et al. 2002

Environ and Mol Mutagen

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Sporadic breast cancer, the most common cancer diagnosed in American and Northern European women, is gradually increasing in incidence in most Western countries. Prevention would be the most efficient way of eradicating this disease. This goal, however, cannot be accomplished until the specific agent(s) or mechanisms that initiate the neoplastic process are identified. Experimental studies have demonstrated that mammary cancer is a hormone-dependent multistep process that can be induced by a variety of compounds and mechanisms, that is, hormones, chemicals, radiation, and viruses, in addition to or in combination with genetic factors. Although estrogens have been shown to play a central role in breast cancer development, their carcinogenicity on human breast epithelial cells (HBECs) has not yet been clearly demonstrated. Breast cancer initiates in the undifferentiated lobules type 1, which are composed of three cell types: highly proliferating cells that are estrogen-receptor negative (ERϪ), nonproliferating cells that are ER positive (ERϩ), and very few (Ͻ1%) ERϩ cells that proliferate. Interestingly, endogenous 17␤-estradiol (E 2 ) is metabolized by the cytochrome P450 enzyme isoforms CYP1A1 and CYP1B1, which also activate benzo[a]pyrene (B[a]P), a carcinogen contained in cigarette smoke. We postulate that if estrogens are carcinogenic in HBECs, they should induce the same transformation phenotypes induced by chemical carcinogens and ultimately genomic changes observed in spontaneously developing primary breast cancers. To test this hypothesis we compared the transforming potential of E 2 on the HBEC MCF-10F with that of B[a]P. Both E 2 and B[a]P induced anchorage-independent growth, colony formation in agar methocel, and loss of ductulogenic capacity in collagen gel, all parameters indicative of cell transformation. In addition, the DNA of E 2 -transformed cells expressed LOH in chromosome 11 at 11q23.3, 11q24.2-q25, and LOH at 13q12-q13. B[a]P-induced cell transformation was also associated with LOH at 13q12-q13 and at 17p13.2. The relevance of these findings is highlighted by the observation that E 2 -and B[a]P-induced genomic alterations in the same loci found in ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma of the breast. Environ. Mol. Mutagen. 39:254-263, 2002.

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Environmental Tobacco Smoke, Genetic Susceptibility, and Risk of Lung Cancer in Never-Smoking Women

Cited by 164 publications

References 39 publications

Dose‐response relationship in tobacco‐related cancers of bladder and lung: A biochemical interpretation

Dose‐response relationship in tobacco‐related cancers of bladder and lung: A biochemical interpretation

Biomarkers of exposure to combustion by-products in a human population in Shanxi, China

Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens

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