title: Carcinogen DNA adducts and the risk of colon cancer: case-control study.
abstract: Colorectal cancer represents 8.5% of all tumours at the King Faisal Specialist Hospital & Research Centre. Environmental and dietary carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) have long been suspected to play a prominent role in colon cancer aetiology. We designed a case-control study to test the hypothesis of whether or not the presence of DNA adducts can play a role in the aetiology of colon cancer. DNA adducts were measured in 24 cancerous and 20 non-cancerous tissue samples of newly diagnosed colon cancer patients by (32)P-post-labelling technique. Normal tissue from 19 hospital patients served as controls. The mean levels of adducts per 10(10) nucleotides in cancerous and non-cancerous tissue were 151.75+/-217.27 and 114.81+/-186.10, respectively; however, only adducts in cancerous tissue were significantly higher than controls (32.78+/-57.51 per 10(10) nucleotides) with p-values of 0.017. No BPDE-DNA adducts were found. No relationship was found between urinary cotinine as a marker of tobacco smoke and 1-hydroxypyrene as an indicator of an individual's internal dose of PAHs and DNA adducts. In a logistic regression model, only adducts in cancerous tissue were associated with the subsequent risk of colon cancer, with an odds ratio of 3.587 (95% confidence interval 0.833-15.448) after adjustment for age and the duration of living in the current region, but of a borderline significance (p=0.086). Although it is difficult to arrive at a definite conclusion from a small dataset, our preliminary results suggest the potential role of DNA adducts in the colon carcinogenesis process. Additional studies with larger sample sizes are needed to confirm our preliminary finding. It is also important to identify the structural characterization of these unknown DNA adducts in order to have a better understanding of whether or not environmental carcinogens play a role in the aetiology of colon cancer.
authors.affiliation: Biological & Medical Research Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. imam@kfshrc.edu.sa
authors.forename: I
authors.initials: I
authors.lastname: Al-Saleh
authors.forename: J
authors.initials: J
authors.lastname: Arif
authors.forename: I
authors.initials: I
authors.lastname: El-Doush
authors.forename: N
authors.initials: N
authors.lastname: Al-Sanea
authors.forename: A Abdul
authors.initials: AA
authors.lastname: Jabbar
authors.forename: G
authors.initials: G
authors.lastname: Billedo
authors.forename: N
authors.initials: N
authors.lastname: Shinwari
authors.forename: A
authors.initials: A
authors.lastname: Mashhour
authors.forename: G
authors.initials: G
authors.lastname: Mohamed
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis; D000328:Adult; D000368:Aged; D002273:Carcinogens / Q000378:metabolism*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000139:chemically induced*; D018736:DNA Adducts / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis*; D012306:Risk
chemical_list: D002273:Carcinogens; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide