Human Lung Carcinogen--DNA Adduct Levels Mediated by Genetic Polymorphisms In Vivo

Kato, Shunji; Bowman, Elise D.; Harrington, Anita M.; Blömeke, Brunhilde; Shields, Peter G.

doi:10.1093/jnci/87.12.902

Cited by 169 publications

(84 citation statements)

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“…For example, the greatest incremental lung cancer risk (sevenfold) for the 'susceptible' CYP1A1 genotype was seen in light smokers, whereas heavy smokers with this genotype had less than twice the risk of heavy smokers without the genotype . A study also showed that the increased level of carcinogen-DNA adduct related to genetic polymorphism was seen only in individuals exposed to levels of procarcinogens below the average level, while adduct levels in individuals exposed to higher levels were similar, regardless of the genetic status of their susceptibility genes (Kato et al, 1995). Thus, the significant effect seen with CYP1A1 in relation to breast cancer risk in our population, but not in Caucasian populations, might be due to the relatively lower levels of procarcinogens among Taiwanese women.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

Huang

et al. 1999

Br J Cancer

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SummaryThe incidence of breast cancer has been greatly increasing in Taiwan over the past two decades. Since cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens or oestrogen, we hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for breast cancer. This hypothesis was evaluated in this case control study of 150 breast cancer patients and 150 healthy controls among Chinese women. Two CYP1A1 polymorphisms were studied, one containing a new Msp1 site and the other located in axon 7 and resulting in the replacement of an isoleucine (Ile) residue by a valine (Val). After simultaneously considering the known or significant risk factors for breast cancer, including the age of study participants, positive family history of breast cancer, early menarche (≤ 13 years), nulliparity and late first full-term pregnancy (≥ 30 years), hormone replacement therapy and smoking, the CYP1A1 Msp1 polymorphism was found to be a significant factor in determining the risk of breast cancer. The homozygous variant was the most susceptible genotype with an adjusted odds ratio of 1.98 (95% confidence interval (CI) = 1.01-3.99) compared with the non-homozygous variants (the homozygous wild-type and the heterozygous variant). In contrast, the CYP1A1 Ile/Val polymorphism was not significantly associated with breast cancer development (adjusted OR = 1.07, 95% CI = 0.64-1.78). Interestingly, the Msp1 polymorphism was especially significant in postmenopausal women, but not in premenopausal women. Further stratification analysis in postmenopausal women who were non-smokers and with no history of hormone replacement therapy showed the cancer risk due to the Msp1 variant to be more significant in women with early menarche. We conclude that CYP1A1 polymorphism is a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan. Further study with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

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Section: Discussionmentioning

confidence: 99%

Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

Huang

et al. 1999

Br J Cancer

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“…Glutathione S-transferases and cytochrome P4501A1 Although early studies suggested a role of GSTM1 deficiency in aromatic-hydrophobic DNA adduct levels (Ryberg et al, 1994;Grinberg-Funes et al, 1994;Shields et al, 1993;Kato et al, 1995) these studies were criticized (Cuzick, 1995) for not defining cigarette smoking exposure adequately and for not having sufficient size to adjust for potential statistical artifacts. Continued work on the GSTs has appeared (Table 1) and more recent studies have included polymorphism of the GSTT1 and GSTP1 genes.…”

Section: Metabolic Polymorphismsmentioning

confidence: 99%

DNA adduct burden and tobacco carcinogenesis

Wiencke

2002

Oncogene

149

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DNA adducts associated with tobacco smoking could provide a marker of biologically effective dose of tobacco carcinogens and improve individual cancer risk prediction. A significant number of clinical and epidemiologic studies have reported associations of increased DNA adduct levels with the occurrence of the prevalent tobacco related cancers including cancer of the lung, head and neck, and bladder. The inducibility of DNA adducts following in vitro treatments using blood lymphocytes also appears to be a risk factor in the development of lung and head and neck cancer. Corroborative evidence pointing to the importance of DNA adducts in tobacco carcinogenesis include numerous studies showing associations of tobacco smoke exposure with the induction of DNA adducts in humans in vivo. Further effort is necessary, however, to more fully characterize the dose -response relationship between smoking and DNA adducts in exposed target and surrogate tissues. The relationship between gene polymorphisms thought to modify tobacco-related cancer risk and DNA adduct levels is complex. Results of some DNA adduct studies (both in vitro and in vivo) appear inconsistent with the epidemiologic findings. This is evident for polymorphisms involving both carcinogen metabolism (e.g. GSTP1) and DNA repair (e.g. XRCC1). Molecular studies of human tumors suggest associations of p53 mutation with DNA adducts and have revealed correlations of DNA adduct levels with somatic alterations (e.g. 3p21 LOH) that are thought to occur at the very earliest stages of tobacco carcinogenesis. More research is needed to assess the relationship between endogenous sources of DNA adducts and tobacco smoke exposure and the relative oncogenic effects of chemically stable versus unstable DNA adducts. Many potentially fruitful new avenues of cancer research are emerging that integrate DNA adduct analyses with assessments of smoking, genetics, diet and ambient air quality. These investigations aim to understand the multifactorial nature of interindividual variability in response to tobacco carcinogens. As these trends continue a variety of innovative study designs and approaches will become important in human populations.

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“…The CYP2D6-A allelic variant was detected using allele-specific double-step PCR according to Heim and Meyer (1990). The CYP2D6-B allele was identified using PCR and BstNI digestion as previously described by Kato et al (1995).…”

Section: Genotyping Of Gstm1 Cyp2d6 and Cyp1a1mentioning

confidence: 99%

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

Rusin¹,

Butkiewicz²,

Małusecka³

et al. 1999

Br J Cancer

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The p53 mutation spectrum can generate hypotheses linking carcinogen exposure to human cancer. Although it is well-documented that tobacco smoking is a major cause of lung cancer, the contribution of air pollution is less well-established. We determined the molecular and immunohistochemical changes ( p53 gene mutations, p53 protein accumulation and WAF1 protein expression) and genetic polymorphisms of GSTM1, CYP1A1 and CYP2D6 genes in a case series of non-small-cell lung cancers from Silesia. This region of southern Poland is highly industrialized with considerable environmental pollution. More than 50% of lung cancers (90/164) contained p53 mutations and 75% showed the combined alteration of the p53 gene and protein accumulation. Males occupationally exposed to coal-derived substances showed a relatively high frequency of squamous and large-cell carcinomas, relatively frequent mutations in codon 298 of p53 and a low frequency of p53 immunohistochemically positive tumours. Codon 298 GAG→ →TAG mutations have rarely been found in lung cancers in other populations. We found no correlation between WAF1 protein expression and mutations in the p53 gene or p53 protein accumulation. No statistically significant relationship was found between p53 mutations and GSTM1, CYP1A1, CYP2D6 genotypes. Never smokers with lung cancers from Silesia had a higher frequency of G:C→ →T:A transversions than previously reported of the p53 mutation spectrum in never smokers (6/15 vs 4/34; P = 0.06 by χ 2 ). These data are a tentative indication that occupational and environmental exposure to polycyclic aromatic hydrocarbons, such as benzo(a)pyrene, in polluted air contributes to the molecular pathogenesis of lung cancer in never smokers. © 1999 Cancer Research Campaign

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Human Lung Carcinogen--DNA Adduct Levels Mediated by Genetic Polymorphisms In Vivo

Cited by 169 publications

References 0 publications

Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

Cytochrome P4501A1 polymorphism as a susceptibility factor for breast cancer in postmenopausal Chinese women in Taiwan

DNA adduct burden and tobacco carcinogenesis

Molecular epidemiological study of non-small-cell lung cancer from an environmentally polluted region of Poland

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