Showing papers by "David Forman published in 2002"

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

Abstract: 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.

Relation of adult lifestyle and socioeconomic factors to the prevalence of Helicobacter pylori infection.

Abstract: Introduction The influence of adult socioeconomic status, co-habitation, gender, smoking, coffee and alcohol intake on risk of Helicobacter pylori infection is uncertain. Methods Subjects between aged 40-49 years were randomly invited to attend their local primary care centre. Participants were interviewed by a researcher on smoking, coffee and alcohol intake, history of living with a partner, present and childhood socioeconomic conditions. Helicobacter pylori status was determined by 13C-urea breath test. Results In all, 32 929 subjects were invited, 8429 (26%) were eligible and 2327 (27.6%) were H. pylori positive. Helicobacter pylori infection was more common in men and this association remained after controlling for childhood and adult risk factors in a logistic regression model (odds ratio [OR] = 1.15; 95% CI: 1.03-1.29). Living with a partner was also an independent risk factor for infection (OR = 1.30; 95% CI: 1.01-1.67), particularly in partners of lower social class (social class IV and V-OR = 1.47; 95% CI: 1.19-1.81, compared with social class I and II). Helicobacter pylori infection was more common in lower social class groups (I and II-22% infected, III-29% infected, IV and V-38% infected) and there was a significant increase in risk of infection in manual workers compared with non-manual workers after controlling for other risk factors (OR = 1.18; 95% CI: 1.03-1.34). Alcohol and coffee intake were not independent risk factors for infection and smoking was only a risk factor in those smoking >35 cigarettes a day. Conclusions Male gender, living with a partner and poor adult socioeconomic conditions are associated with increased risk of H. pylori infection.

Counting cancers at the junction - a problem of routine statistics.

Abstract: The increase over time in the incidence of cancer arising at the oesophagogastric junction has been the subject of many papers reviewing data obtained from cancer registries and other sources of routine statistics. The analysis of such data is beset with a number of problems, all of which compromise comparability over time and hence complicate interpretation. This makes it extremely difficult to assess with any degree of reliability the quantitative extent to which these cancers really are increasing. Some recent datasets, such as from the Eindhoven Cancer Registry, are now providing higher-quality information that can remedy this deficiency. In the absence of such routine information, useful insights can be obtained from analysis of appropriate clinical datasets that exist in Japan.

Helicobacter pylori eradication therapy for nonulcer dyspepsia.

Abstract: TO THE EDITOR: We were interested to read the systematic review by Laine and colleagues (1) suggesting that Helicobacter pylori eradication therapy was not effective in nonulcer dyspepsia. We previously published a systematic review within the Cochrane Collaboration that reached a different conclusion (2), namely, that H. pylori eradication was associated with an increase in cure of symptoms in nonulcer dyspepsia. The effect size we observed was modest (reduction in dyspepsia rate, 9% [95% CI, 5% to 14%]) but statistically significant (P 0.001), and an economic analysis suggested that H. pylori eradication may be cost-effective in patients with nonulcer dyspepsia (3). This conclusion was maintained in all sensitivity analyses and did not depend on the results of any one trial. We believe that our results differed from those of Laine and colleagues mainly because our review currently includes studies published up to May 2000 and Laine and colleagues curtailed their search in December 1999. Therefore, we included nine trials evaluating 2541 patients while Laine and colleagues included only seven trials and 1544 patients. In our analysis, we included abstracts only when authors provided further information, and we actually revised the results of one abstract (4). We summarized results by using risk ratios for continuing dyspepsia, while Laine and colleagues used odds ratios for cure (5). If Laine and colleagues had applied our methods, they would have found their results to be statistically significant. Laine and colleagues reached their particular conclusion mainly because they had not included the most recent trials in their systematic review. The advantage of Cochrane systematic reviews is that they are continually updated, and time between submission and publication is short. This is particularly important in areas that are rapidly evolving, such as H. pylori eradication in nonulcer dyspepsia. There is now substantial evidence that H. pylori eradication has a beneficial effect on patients with this disorder.