Gillian Smith — Page 2

PubMed2002

A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer.

Susceptibility to colorectal cancer, one of the most common forms of cancer in the Western world, has been associated with several environmental and dietary risk factors. Dietary exposure to food derived heterocyclic amine carcinogens and polycyclic aromatic hydrocarbons have been proposed as specific risk factors. Many polymorphic Phase I and Phase II drug metabolizing enzymes are responsible for the metabolism and disposition of these compounds and it is therefore possible that inheritance of specific allelic variants of these enzymes may influence colorectal cancer susceptibility. In a multicenter case-control study, 490 colorectal cancer patients and 593 controls (433 matched case-control pairs) were genotyped for common polymorphisms in the cytochrome P450 (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C9, CYP2C19 and CYP2D6), glutathione S-transferase (GSTM1, GSTP1 and GSTT1), sulfotransferase (SULT1A1 and SULT1A2), N-acetyl transferase 2 (NAT2), NAD(P)H:quinone oxidoreductase (NQO1), methylenetetrahydrofolate reductase (MTHFR), and microsomal epoxide hydrolase (EPHX1) genes. Matched case-control analysis identified alleles associated with higher colorectal cancer risk as carriage of CYP1A1*2C (OR = 2.15, 95% CI 1.36-3.39) and homozygosity for GSTM1*2/*2 (OR = 1.53, 95% CI 1.16-2.02). In contrast, inheritance of the CYP2A6*2 (OR = 0.51, 95% CI 0.28-1.06), CYP2C19*2 (OR = 0.72, 95% CI 0.52-0.98) and the EPHX1(His113) alleles were associated with reduced cancer risk. We found no association with colorectal cancer risk with NAT2 genotype or any of the other polymorphic genes associated with the metabolism and disposition of heterocyclic amine carcinogens. This data suggests that heterocyclic amines do not play an important role in the aetiology of colorectal cancer but that exposure to other carcinogens such as polycyclic aromatic hydrocarbons may be important determinants of cancer risk.

Adenocarcinoma↗

PubMed2002

Helicobacter pylori susceptibility testing by disc diffusion.

The bacterium Helicobacter pylori is found in c. 40% of the population and is responsible for the development of duodenal disease. Triple treatment with a proton-pump inhibitor or bismuth salt plus two antibiotics is now commonplace in all patients diagnosed. As antibiotic resistance reduces treatment efficacy, it is time to consider routine susceptibility testing to guide individual patient treatment and surveillance of antibiotic resistance. There are no published nationally agreed standards for disc diffusion testing of H. pylori. After reviewing the literature, we recommend the following method for disc diffusion tests. A suspension of cultures < or = 4 days old equivalent to McFarland Standard no. 4 (10(8) cfu/mL) should be used on Mueller-Hinton or Columbia agar base with 5-10% blood, using a metronidazole disc strength of 5 Ig and a clarithromycin disc strength of 2 microg. Anaerobic pre-incubation of plates is unnecessary. A H. pylori control susceptible to metronidazole (e.g. NCTC 12822) should be used. Zone sizes with the Mueller-Hinton agar base for metronidazole testing are <16 mm resistant, 16-21 mm intermediate and >21 mm susceptible. We suggest that isolates in the intermediate zone should be re-tested by Etest. Zone sizes with the Columbia agar base for metronidazole testing are <10 mm resistant and > or = 10 mm susceptible. Co-infection with two strains, which may be a mixture of isolates susceptible and resistant to metronidazole leading to conflicting susceptibility results, occurs in 5-10% of patients. Zone sizes with Mueller-Hinton agar and Columbia blood agar for clarithromycin testing are resistant no zone and susceptible any zone.

Anaerobiosis↗