Cigarette smoking related polycyclic aromatic hydrocarbon—DNA adducts in peripheral mononuclear cells

Cancer Epidemiology, Biomarkers &Amp; Prevention

Terry

et al. 2007

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Genes involved in the nucleotide excision repair (NER) pathway, which removes bulky DNA adducts, are potential low-penetrance cancer susceptibility genes. We recently reported an association between detectable polycyclic aromatic hydrocarbon (PAH)-DNA adducts and breast cancer risk. Using a population-based breast cancer case-control study on Long Island, New York, we examined whether polymorphisms in NER genes modified the association between PAH-DNA adducts and breast cancer risk. We examined polymorphisms in ERCC1 (3 ¶-untranslated region 8092C/A), XPA (5 ¶-untranslated region À4G/A), XPD (Asp 312 Asn in exon 10), XPF (Arg 415 Gln in exon 8), and XPG (Asp 1104 His in exon 15) in 1,053 breast cancer cases and 1,102 population-based controls. The presence of at least one variant allele in XPD was associated with a 25% increase in the odds ratio [OR, 1.25; 95% confidence interval (95% CI), 1.04-1.50] for breast cancer. The increase associated with homozygosity of the variant alleles for XPD and ERCC1 was stronger among those with detectable PAH-DNA adduct levels (OR, 1.83; 95% CI, 1.22-2.76 and OR, 1.92; 95% CI, 1.14-3.25 for detectable versus nondetectable adducts and homozygous wild-type genotype for XPD and ERCC1, respectively). We found no association between XPA, XPF, and XPG genotypes, PAH-DNA adducts, and breast cancer risk. When we combined genotypes for these NER pathway genes, there was a significant trend for increasing breast cancer risk with increasing number of putative high-risk alleles. Overall, this study suggests that the risk of breast cancer may be elevated among women with polymorphisms in NER pathway genes and detectable PAH-DNA adducts. (Cancer Epidemiol Biomarkers Prev 2007;16(10):2033 -41)

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in Nucleotide Excision Repair Genes, Polycyclic Aromatic Hydrocarbon-DNA Adducts, and Breast Cancer Risk

Crew

Cancer Epidemiology, Biomarkers &Amp; Prevention

Terry

et al. 2007

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“…Competitive ELISA (Poirier et al, 1980;Santella et al, 1992) was used to analyze the PAH diol epoxide-DNA adducts (Gammon et al, 2002a(Gammon et al, , 2005. Laboratory personnel were blinded to case-control status when they ran the samples in duplicate, and mean values were used to determine the percentage inhibition.…”

Section: Laboratory Methodsmentioning

confidence: 99%

Residential environmental exposures and other characteristics associated with detectable PAH-DNA adducts in peripheral mononuclear cells in a population-based sample of adult females

Shantakumar

J Expo Sci Environ Epidemiol

Eng

et al. 2005

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The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25 þ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n ¼ 796). Environmental home samples of dust (n ¼ 356) and soil (n ¼ 360) were collected on a random subset of long-term residents (15 þ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR ¼ 2.65, 95% confidence interval (CI) ¼ 1.69, 4.17; OR ¼ 1.59, 95% CI ¼ 1.08, 2.32, respectively), as did current and past smokers (OR ¼ 1.50, 95% CI ¼ 1.00, 2.24; OR ¼ 1.46, 95% CI ¼ 1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking.

“…16,17 Samples were run with the lab blinded to case-control status, in duplicate, and mean values were used for determination of percentage inhibition. For analytical purposes, those samples with Ͻ 15% inhibition were considered nondetectable and assigned a value of 1/10 8 -an amount midway between the lowest positive value and zero.…”

mentioning

confidence: 99%

“…As reviewed by Santella et al, 17 adducts reflect both PAH exposure and the body's response. PAHs are detoxified in the body through P450 and glutathione s-transferase (GST) pathways, and incomplete detoxification results in DNA damage, which can be reversed by normal DNA repair mechanisms.…”

mentioning

confidence: 99%

Polycyclic Aromatic Hydrocarbon–DNA Adducts and Breast Cancer: A Pooled Analysis

Archives of Environmental Health: An International Journal

Sagiv

Eng

et al. 2004

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106

ABSTRACT. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts have been associated with breast cancer in several small studies. The authors' pooled analysis included 873 cases and 941 controls from a population-based case-control study. Competitive enzyme-linked immunosorbent assay in peripheral mononuclear cells was conducted in 2 rounds, and results were pooled on the basis of round-specific quantiles. The odds ratio for breast cancer was elevated in relation to detectable PAH-DNA adducts (1.29 as compared with nondetectable adduct levels; 95% confidence interval ϭ 1.05, 1.58), but there was no apparent dose-response relationship with increasing quantiles. No consistent pattern emerged when