Aromatic DNA Adducts and Risk of Gastrointestinal Cancers: A Case–Cohort Study within the EPIC–Spain

Agudo, Antonio; Peluso, Marco; Munnia, Armelle; Luján-Barroso, Leila; Sánchez, María‐José; Molina‐Montes, Esther; Sánchez‐Cantalejo, Emilio; Navarro, Carmen; Tormo, María-José; Chirlaque, María‐Dolores; Barricarte, Aurelio; Ardanaz, Eva; Amiano, Pilar; Dorronsoro, Miren; Quiŕos, J. Ramón; Piro, Sara; Bonet, Catalina; Sala, Núria; González, Carlos A.

doi:10.1158/1055-9965.epi-11-1205

Cited by 28 publications

(21 citation statements)

References 30 publications

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“…However, this study was limited by a relatively small number of cases of colorectal adenoma (N=82), and blood samples were collected after diagnosis. More recently, Agudo et al [12] conducted a case-cohort study evaluating the relationship between aromatic DNA adduct levels in pre-diagnostic leukocytes and risk of colorectal cancer (154 cases). The investigators reported a statistically significant increased risk of colorectal cancer with increasing levels of aromatic DNA adducts, and observed a stronger association for colon cancer than for rectal cancer.…”

Section: Discussionmentioning

confidence: 99%

“…However, few studies have evaluated the relationship between PAH exposure biomarkers and risk of colorectal adenoma [11] or colorectal cancer [12]. In this nested case–control study, we evaluated the risk of colorectal cancer in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a metabolite of pyrene and an established biomarker of PAH exposure [13], among participants in the Shanghai Women’s Health Study.…”

Section: Introductionmentioning

confidence: 99%

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Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women’s Health Study

et al. 2013

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BackgroundAssociations between polycyclic aromatic hydrocarbons (PAHs) and colorectal cancer have been reported previously but few studies have characterized PAH exposure using biological measurements. We evaluated colorectal cancer risk in relation to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG), a polycyclic aromatic hydrocarbon (PAH) metabolite, and assessed determinants of PAH exposure among controls in the Shanghai Women’s Health Study (SWHS).MethodsConcentrations of 1-OHPG were measured in spot urine samples collected from 343 colorectal cancer cases and 343 individually matched controls. Questionnaires were administered to collect information on demographic characteristics and reported exposures. Odds ratios were calculated for risk of colorectal cancer in relation to quartiles of urinary 1-OHPG concentration. Potential determinants of natural log-transformed urinary 1-OHPG concentration were evaluated among a combined sample of controls from this study and another nested case–control study in the SWHS (Ntotal=652).ResultsNo statistically significant differences in risk of colorectal cancer by urinary 1-OHPG levels were observed. Among controls, the median (interquartile range) urinary 1-OHPG concentration was 2.01 pmol/mL (0.95-4.09). Active and passive smoking, using coal as a cooking fuel, eating foods that were cooked well done, and recent consumption of fried dough (e.g., yóutiáo) were associated with elevated levels of 1-OHPG, though only active smoking and fried dough consumption achieved statistical significance in multivariate analyses.ConclusionsThis study does not provide evidence of an association between urinary levels of 1-OHPG and risk of colorectal cancer among women. Several environmental and dietary sources of PAH exposure were identified. Overall, the levels of 1-OHPG in this population of predominantly non-smoking women were considerably higher than levels typically observed among non-smokers in Europe, North America, and other developed regions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women’s Health Study

et al. 2013

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“…However, 32 P‐postlabeling is labor‐intensive and requires large amounts of hazardous radioactivity, the technique is not quantitative, and structural information about the identity of the adduct is uncertain, particularly in humans where many overlapping lesions are present . Thus, epidemiology studies employing 32 P‐postlabeling often provide ambiguous data about chemical exposures linked to DNA adducts and cancer risk …”

Section: Methods To Biomonitor Dna Adducts In Humansmentioning

confidence: 99%

DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans

Yun

Guo

Bellamri

et al. 2018

Mass Spectrometry Reviews

106

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Hazardous chemicals in the environment and diet or their electrophilic metabolites can form adducts with genomic DNA, which can lead to mutations and the initiation of cancer. In addition, reactive intermediates can be generated in the body through oxidative stress and damage the genome. The identification and measurement of DNA adducts are required for understanding exposure and the causal role of a genotoxic chemical in cancer risk. Over the past three decades, P-postlabeling, immunoassays, gas chromatography/mass spectrometry, and liquid chromatography/mass spectrometry (LC/MS) methods have been established to assess exposures to chemicals through measurements of DNA adducts. It is now possible to measure some DNA adducts in human biopsy samples, by LC/MS, with as little as several milligrams of tissue. In this review article, we highlight the formation and biological effects of DNA adducts, and highlight our advances in human biomonitoring by mass spectrometric analysis of formalin-fixed paraffin-embedded tissues, untapped biospecimens for carcinogen DNA adduct biomarker research.

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“…Many DNA adducts serve as biomarkers of carcinogenic PAH exposure and cancer risk (Phillips and Venitt 2012; Poirier 1997; Urban et al 2012). Significant positive linear correlations between levels of PAH-DNA adducts and cancer incidence have been reported in both epidemiological studies (Agudo et al 2012; Tang et al 2001; Veglia et al 2008) and animal experiments (Culp et al 1998). However, negative correlations between PAH-DNA adducts and tumor incidence have also been observed (Saieva et al 2011; Siddens et al 2012) and the mechanic relationships between carcinogen-DNA adducts and tumor formation are still not fully understood.…”

Section: Introductionmentioning

confidence: 96%

Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures

et al. 2014

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The genotoxicity of a complex mixture [neutral fraction (NF)] from a wood preserving waste and reconstituted mixture (RM) mimicking the NF with seven major polycyclic aromatic hydrocarbons (PAHs) and benzo(a)pyrene (BaP) was investigated by determining DNA adducts and tumor incidence in male B6C3F1 mice exposed to 3 different doses of the chemical mixtures. The peak values of DNA adducts were observed after 24 h and the highest levels of PAH-DNA adducts were exhibited in mice administered NF+BaP, and the highest tumor incidence and mortality were also observed in this group. DNA adduct levels after 1, 7, or 21 d were significantly correlated with animal mortality and incidence of total tumors including liver, lung, and forestomach. However, only hepatic DNA adducts after 7 d significantly correlated with liver tumor incidence. Most proteins involved in DNA repair including ATM, pATR, Chk1, pChk1, DNA PKcs, XRCC1, FANCD2, Ku80, Mre11 and Brca2 were significantly lower in liver tumor tissue compared to non-tumor tissue. Expression of proteins involved in apoptosis and cell cycle regulation were also significantly different in tumor vs non-tumor tissues and it is possible that PAH-induced changes in these gene products are important for tumor development and growth.

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Aromatic DNA Adducts and Risk of Gastrointestinal Cancers: A Case–Cohort Study within the EPIC–Spain

Cited by 28 publications

References 30 publications

Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women’s Health Study

Polycyclic aromatic hydrocarbons: determinants of urinary 1-hydroxypyrene glucuronide concentration and risk of colorectal cancer in the Shanghai Women’s Health Study

DNA adducts: Formation, biological effects, and new biospecimens for mass spectrometric measurements in humans

Mechanistic relationships between hepatic genotoxicity and carcinogenicity in male B6C3F1 mice treated with polycyclic aromatic hydrocarbon mixtures

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