Tuesday, July 31, 2001

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""All happy families are more or less like one another: every unhappy family is unhappy in its own particular way." In his opening line to Anna Karenina, Tolstoy might well have been referring to breast cancer families. While two genes responsible for about 15% of hereditary breast cancer, BRCA1 and BRCA2, have been found, researchers have had little success finding a single gene that is responsible for the bulk of hereditary breast cancer. And prospects remain gloomy, according to Doug Easton, co-discoverer of BRCA2, speaking last week at the 25th Annual Meeting of the Human Genetics Society of Australasia in Cairns."

"In other words, the intrinsic problem may be akin to that which Tolstoy identified. Each different family may have a different collection of predisposing genes, and when family studies are combined, the separate findings merely obliterate each other."

"This line of thinking suggests family studies may not be able to yield more predisposition genes. An alternative approach is to sift through the genomes of huge numbers of breast cancer cases and controls, looking for those gene variants that clearly differ in the two populations. Gene variants under-represented in the cases might be protective; those over-represented could be risk genes."

redux [03.20.01]
BreastLink Both Genes and Environment Play Role in Causing Cancer

"The study?s analysis suggests that having a gene associated with a particular cancer does not mean that the individual carrying that gene will inevitably develop cancer. Even a person whose identical twin develops cancer has less than a 15 percent chance of having the same kind of cancer. This study thus introduces a much needed shot of reality into the media portrayal of fatalism and inevitability surrounding the issue of genetic heritage.

The study also points to a need for accelerated research into the extent to which genes interact with the environment to affect an individual?s susceptibility to disease. Most importantly, this and similar studies make it abundantly clear that the nature-versus-nurture argument is based on a false and arbitrary separation."

redux [05.26.00]
British Medical Journal Both Genes and Environment Play Role in Causing Cancer

"Research in disease aetiology has shifted towards investigating genetic causes, powered by the human genome project. Successful identification of genes for monogenic disease has led to interest in investigating the genetic component of diseases that are often termed complex, that is, they are known to aggregate in families but do not segregate in a mendelian fashion. Genetic epidemiology has permitted identification of genes affecting people's susceptibility to disease, although progress has been much slower than many people expected. While the role of genetic factors in diseases such as hypertension, asthma, and depression is being intensively studied, family studies and the large geographical and temporal variation in the occurrence of many diseases indicate a major role of the environment. Thus, it is necessary to consider findings about susceptibility genes in the context of a population and evaluate the role of genetic factors in relation to other aetiological factors. This article discusses some approaches used to resolve the genetic architecture of disease and to study the relation of genes to environmental factors in the population."

redux [11.16.00]
The Centers for Disease Control The Future of Genetic Studies of Complex Human Diseases: An Epidemiologic Perspective

"With advances in the human genome project and the increasing availability of DNA markers scattered throughout the genome such as simple sequence polymorphisms, variable number tandem repeats, and short sequence repeat polymorphisms, it has become increasingly possible to search for the genetic basis of complex human diseases using genomic wide screening methods. Linkage analysis using LOD score analysis in large pedigrees has been the traditional tool to identify gene loci for human disorders both for single gene disorders (e.g. Huntington) and for complex chronic diseases (e.g. bipolar disease). Recently, Risch and Merikangas have argued that the future of genetic studies of complex human disease may depend, to a large extent, on applications of new "association" type methods to family-based data. The main method of interest is the transmission disequilibrium test (TDT) in which alleles at a given locus for a person with a specific disease are compared with parental non transmitted alleles, to look for evidence of deviation from expectations in the absence of linkage. The TDT has been shown to be a valid test of linkage in the presence of linkage disequilibrium (which creates associations with specific alleles). They showed that the TDT has more power than traditional linkage analysis for disease genes with weak to moderate effects on disease risks.

In this paper, we argue that the future of the genetic study of complex disorders will rely increasingly on the classical epidemiologic "association" paradigm. We show that on the long run, improvements in study designs and in adjusting for population stratification using interviews and genetics markers will lead to a new era of population-based incident case-control studies that could have more power and lead to more detailed information not only on the presence or absence of a disease susceptibility gene but define the magnitude of risks and gene-environment interaction- a crucial first step to disease prevention and health promotion."