Misclassification in case-control studies of gene-environment interactions: assessment of bias and sample size.

In studies of gene-environment interactions, exposure misclassification can lead to bias in the estimation of an interaction effect and increased sample size. The magnitude of the bias and the consequent increase in sample size for fixed misclassification probabilities are highly dependent on the prevalence of the misclassified factor and on the interaction model. This paper describes a relatively simple approach to assess the impact of misclassification on bias in the estimation of multiplicative or additive interactions and on sample size requirements.

Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility.

Background: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk.

The impact of misclassification in case-control studies of gene-environment interactions.

In this chapter we describe the impact of risk factor misclassification in case-control studies designed to estimate gene-environment interactions. We show that under certain scenarios even small amounts of exposure or genotype misclassification can substantially attenuate the interaction effect and, as a consequence, dramatically increase the sample size required to study these interactions. A consideration of how sample size is affected by exposure and genotype misclassification in the study design phase should help to identify situations where obtaining better risk factor information is crucial for the feasibility of studies.

Well-done, grilled red meat increases the risk of colorectal adenomas.

Red meat or meat-cooking methods such as frying and doneness level have been associated with an increased risk of colorectal and other cancers. It is unclear whether it is red meat intake or the way it is cooked that is involved in the etiology of colorectal cancer. To address this issue, we developed an extensive food frequency questionnaire module that collects information on meat-cooking techniques as well as the level of doneness for individual meat items and used it in a study of colorectal adenomas, known precursors of colorectal cancer.

Epidemiologic determinants of vaginal pH.

Objectives: This study was undertaken to evaluate the relationship between vaginal pH and factors related to cervical cancer.

Study Design: In a population-based sample of 9161 women from Guanacaste Province in Costa Rica women were categorized into 2 groups, those with vaginal pH in the reference range (4.0-4.

Power and sample size calculations in case-control studies of gene-environment interactions: comments on different approaches.

Power and sample size considerations are critical for the design of epidemiologic studies of gene-environment interactions. Hwang et al. (Am J Epidemiol 1994;140:1029-37) and Foppa and Spiegelman (Am J Epidemiol 1997;146:596-604) have presented power and sample size calculations for case-control studies of gene-environment interactions.

A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer.

Carcinogenic heterocyclic amines are activated by N-acetyltransferase (NAT) enzymes, encoded by NAT1 and NAT2, to genotoxic compounds that can form DNA adducts in the colon epithelium. We have examined the relation of polymorphisms in the genes coding for both enzymes to risk of colorectal cancer and the gene-environment interaction with red meat intake among participants in the prospective Physicians' Health Study. Baseline blood samples from 212 men subsequently diagnosed with colorectal cancer during 13 years of follow-up were genotyped, along with 221 controls.

Differential misclassification and the assessment of gene-environment interactions in case-control studies.

In case-control studies of interactions between genetic and environmental exposures, differential misclassification of the environmental exposure with respect to disease status can introduce spurious heterogeneity of the stratum-specific odds ratios. In this paper, the authors identify conditions under which differential misclassification does not introduce bias in the interaction parameter when no multiplicative interaction is present, and it biases the interaction parameter toward the null value when a multiplicative interaction is present. The conditions are that (i) conditional on potential confounders, the environmental exposure is independent of the genotype among the controls, and (ii) misclassification of the environmental exposure is nondifferential with respect to the genotype.

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators.

A cross-sectional study of dental caries, intake of confectionery and foods rich in starch and sugars, and salivary counts of Streptococcus mutans in children in Spain.

In this cross-sectional study of 236 schoolchildren living in Manresa, Spain, we evaluated the association between prevalence of dental caries and frequency of consumption of various food groups, including sweetened baked goods and similar foods (rich in starch and sugars) and confectionery (rich in sugars but not starch), using a food-frequency questionnaire. Because Streptococcus mutans is associated with the cariogenicity of carbohydrates, we also evaluated the modification of these associations by salivary counts of this microorganism. Odds ratios (ORs) were used to measure the association between caries and tertiles of consumption.

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States).

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant.

Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases.

A common deletion polymorphism in the gene coding for the glutathione S-transferase class mu (the GSTM1 gene) results in a decreased ability to detoxify carcinogenic epoxide intermediates and has been associated with increased breast cancer risk in some small studies. We studied the GSTM1 gene deletion polymorphism (conferring the null genotype) in 243 women who had prevalent breast cancer and 245 women without breast cancer, who were among the 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. In the prevalent case series, the null genotype was slightly more common among cases (58%) than among controls (51%; age-adjusted odds ratio = 1.

Asbestos-related diseases in construction carpenters.

To assess the association of minimal parenchymal fibrosis and pleural plaques with respiratory functional impairment, we conducted a survey of 631 asbestos-exposed construction carpenters. This population had a relatively low prevalence of radiographic abnormalities and lung function impairment. Pleural plaques was the asbestos-related disease most prevalent, followed by interstitial fibrosis with predominantly low profusion scores.

Variability of nasal lavage polymorphonuclear leukocyte counts in unexposed subjects: its potential utility for epidemiology.

Recent studies have utilized nasal lavage to study the inflammatory cells of the nasal epithelium. In unexposed subjects, investigators have reported wide interindividual variability in lavage cell counts. The intraindividual variability of cell counts in sequential lavages has been less well described.