We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption.

Background: Mammography screening may reduce breast cancer mortality by detecting cancers at an earlier stage. However, certain questions remain, including the ideal interval between mammograms. Methods: We conducted an observational study using information collected by seven mammography registries across the United States to investigate whether women diagnosed with breast cancer after having screening mammograms separated by a 2-year interval (n = 2440) are more likely to be diagnosed with late-stage disease (positive lymph nodes or metastases) than women diagnosed with breast cancer after having screening mammograms separated by a 1-year interval (n = 5400). Analyses were stratified by age and breast density to clarify whether groups that have the poorest mammography sensitivity (i.e., women under age 50 years and those with mammographically dense breasts) would benefit most from annual screening. The subjects were women diagnosed with breast cancer between 1996 and 2001 who were 40–89 years old at their index mammographic examination (i.e., the most recent screen at or before breast cancer diagnosis). Data were analyzed by logistic regression, adjusting for race, ethnicity, family history of breast cancer, and mammography registry. Results: Among women age 40–49 years at the index mammogram, those with a 2-year screening interval were more likely to have late-stage disease at diagnosis than those with a 1-year screening interval (28% versus 21%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.01 to 1.81). There was no increase in late-stage disease for women 50 years or older with a 2-year versus a 1-year screening interval (women age 50–59 years at index mammogram: OR = 0.97, 95% CI = 0.75 to 1.25; women age 60–69 years at index mammogram: OR = 0.99, 95% CI = 0.72 to 1.35; women age 70 years or older at index mammogram: OR = 0.88, 95% CI = 0.64 to 1.19). There was no indication that women with dense breasts would benefit more from a 1-year versus 2-year screening interval than women with fatty breasts. Conclusion: These findings may be useful for policy decisions about appropriate screening intervals and for use in statistical models that estimate the costs and benefits of mammography by age and screening interval.

The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools containing Grades 6 through 9. Australian children using Consider This reported reduced 30-day smoking prevalence. This reduction was mediated by decreased subjective norms. The amount of program exposure was low in many classes, but program use displayed a dose-response relationship with reduced smoking prevalence. American children only reported lower expectations for smoking in the future. Intervening to prevent smoking is a challenge, and this data suggest small benefits from an Internet-based program that are unlikely to be of practical significance unless increased by improved implementation. Implementation remains the major challenge to delivering interventions via the Internet, both for health educators and researchers.