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High-risk Families (high-risk + family)
Selected AbstractsSerum homocysteine, creatinine, and glucose as predictors of the severity and extent of coronary artery disease in asymptomatic members of high-risk familiesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2002P. Pajunen Abstract Background There has been no previous study to determine the severity and extent of coronary artery disease (CAD) in subjects with no diagnosis or symptoms of CAD at the time of the angiography. Methods Fifty-three subjects, who were siblings of patients with early onset CAD, underwent coronary angiography. Indices to describe per-patient characteristics of CAD were calculated, based on computer-aided quantitative coronary angiography. Clinical and laboratory characteristics were correlated to the angiographic parameters. Results Serum total homocysteine (, = 0·29, P < 0·05) and creatinine (, = 0·47, P = 0·001) levels were related to the global atheroma burden index. The median of the atheroma burden index was two times higher in the top homocysteine quartile compared to the lowest quartile. The overall atheroma burden index correlated significantly with the fasting blood glucose level in all subjects. Diabetes, especially when albuminuria was present, was a powerful risk factor. In a multivariate analysis, only age and sex were independent predictors of atheroma burden. Conclusions Serum homocysteine and creatinine concentrations, and diabetes with albuminuria were found to be markers of the severity and extent of CAD in subjects of high-risk families without symptoms of CAD. [source] Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi StudyGENETIC EPIDEMIOLOGY, Issue 2 2001Nilanjan Chatterjee Abstract When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401,1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6,2.6) but has little or no effect on the carriers. Genet. Epidemiol. 21:123,138, 2001. © 2001 Wiley-Liss, Inc. [source] Cancer patterns in nasopharyngeal carcinoma multiplex families in TaiwanINTERNATIONAL JOURNAL OF CANCER, Issue 7 2009Kelly J. Yu Abstract Genetic and environmental factors have been implicated in the etiology of nasopharyngeal carcinoma (NPC), a tumor known to be closely associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC and have suggested the possible aggregation of NPC and other cancers. We evaluated familial aggregation of cancer in 358 high-risk families with two or more NPC cases enrolled in a NPC genetics study in Taiwan. Participants were linked to the Taiwan National Cancer Registry to identify incident cancers diagnosed after study enrollment (started in 1996) and before December 31, 2005, or death. In total, 2,870 individuals from the NPC Multiplex Family Study contributed 15,151 person-years over an average of 5.3 years of follow-up. One hundred ten incident cancers were identified. Multiple-primary standardized incidence ratios (MP-SIRs) were computed to evaluate overall cancer risk associated with infectious agents and with other tumors. The overall MP-SIR was 1.3 (95% CI: 1.1,1.6), which was largely explained by an excess in NPC (MP-SIR = 15; 95% CI: 10,23). Exclusion of incident NPC diagnoses led to an overall MP-SIR of 1.0 (95% CI: 0.83,1.3). Similarly, the observed excess risk of cancers associated with infectious agents (MP-SIR = 2.0; 95% CI: 1.5,2.6) was driven by the excess in NPC; exclusion of NPC cases led to a reduced MP-SIR that did not differ from 1.0. Analysis of the largest NPC multiplex family study to date confirms the presence of coaggregation of NPC within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. © 2008 Wiley-Liss, Inc. [source] Childhood Sleep Problems, Response Inhibition, and Alcohol and Drug Outcomes in Adolescence and Young AdulthoodALCOHOLISM, Issue 6 2010Maria M. Wong Background:, To our knowledge, no prospective studies examine the relationships among childhood sleep problems, adolescent executive functioning, and substance outcomes (i.e., substance use and substance-related problems). In this study, we examined whether childhood sleep problems predicted adolescent sleep problems and response inhibition. We also tested whether adolescent sleep problems and poor response inhibition mediated the relationship between childhood sleep problems and substance (alcohol and drug) outcomes in young adulthood. Methods:, Study participants were 292 boys and 94 girls (M = 4.85, SD = 1.47) from a community sample of high-risk families and controls. Results:, When compared to their counterparts, those with trouble sleeping in childhood were twice as likely to have the same problem in adolescence. Childhood overtiredness predicted poor response inhibition in adolescence. Persistent trouble sleeping from childhood to adolescence and response inhibition in adolescence mediated the relationship between childhood sleep problems and drug outcomes in young adulthood, whereas overtiredness in childhood directly predicted alcohol use outcomes and alcohol-related problems in young adulthood. Conclusions:, This is the first study showing a long-term relationship between childhood sleep measures and subsequent alcohol and drug outcomes. The developmental and clinical implications of these findings were discussed. Prevention and intervention programs may want to consider the role of sleep problems and response inhibition on substance use and abuse. [source] Sleep Problems in Early Childhood and Early Onset of Alcohol and Other Drug Use in AdolescenceALCOHOLISM, Issue 4 2004Maria M. Wong Abstract: Background: No prospective studies exist on the relationship between sleep problems early in life and subsequent alcohol use. Stimulated by the adult literature linking sleep problems to the subsequent onset of alcohol use disorders in some adults, we examined whether sleep problems in early childhood predicted the onset of alcohol and other drug use in adolescence and whether such a relationship was mediated by other known predictors of this relationship, namely, attention problems, anxiety/depression, and aggression in late childhood. Methods: This study is part of an ongoing longitudinal study of the development of risk for alcohol and other substance use disorders. Study participants were 257 boys from a community-recruited sample of high-risk families. Results: Mothers' ratings of their children's sleep problems at ages 3 to 5 years significantly predicted an early onset of any use of alcohol, marijuana, and illicit drugs, as well as an early onset of occasional or regular use of cigarettes by age 12 to 14. Additionally, although sleep problems in early childhood also predicted attention problems and anxiety/depression in later childhood, these problems did not mediate the relationship between sleep problems and onset of alcohol and other drug use. Conclusions: This is, to our knowledge, the first study that prospectively examines the relationship between sleep problems and early onset of alcohol use, a marker of increased risk for later alcohol problems and alcohol use disorders. Moreover, early childhood sleep problems seem to be a robust marker for use of drugs other than alcohol. Implications for the prevention of early alcohol and other drug use are discussed. [source] | ||||||||||