ViewpointMisconceptions about the use of genetic tests in populations
Section snippets
Genetic penetrance and environmental factors
The prospect of genetic screening for preventable or deferrable disease is becoming real. As the cataloguing of the human genome proceeds, the rate at which specific genes are being implicated in disease processes is increasing. Because of its genetic basis, much interest has centred on identification of genes for cancer and their usefulness in routine screening. Cost-benefit analysis is urgently needed for screening for single-gene diseases versus multigenetic diseases, and for genes of low
Numbers needed to screen
To assess the role of a gene-environment interaction and screening in a population we need to know the penetrance of the genetic trait and its frequency. A useful approach is to combine penetrance and frequency by computing the number needed to screen (NNS) in order to prevent one case of cancer. The calculation is explained with a worked example in the panel.
Table 1 contains a calculation of NNS in high-risk families for a high-penetrant gene (BRCA1). The cumulative (lifetime) risk of breast
Genetic testing or reduction of exposures
The major diseases in western societies are multifactorial. Thus, lung cancer is not wholly attributable to smoking, but to many linked factors of which smoking is one.
Conversely, smoking also contributes to cardiovascular and other chronic diseases. Elimination of a single environmental exposure (eg, smoking) would reduce a large proportion18 of chronic diseases (table 2). Genetic traits, however, can have a different relation with disease; people with the NAT-2-slow genotype have an increased
False metaphors for DNA
Overall, the proportion of diseases attributable to low-penetrant genetic traits is clearly difficult to establish and is probably much lower than the burden of disease attributable to certain environmental agents. Workers generally agree that less than 5% of cancers are attributable to high-penetrant genes,2 although little is known for other chronic diseases. In general, we can expect little from genetic screening of the population, apart from limited groups (usually families) with a
References (24)
- et al.
Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women
Lancet
(1998) - et al.
Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial
Lancet
(1998) - et al.
BRCA1 and BRCA2 gene mutations and risk of breast cancer: public health perspectives
Am J Prev Med
(1999) - et al.
β2–adrenoceptor gene polymorphism, body weight, and physical activity
Lancet
(1999) The performance of a lifetime: a metaphor for the phenotype
Perspect Biol Med
(1999)- et al.
The genetic basis of human cancer
(1998) - et al.
Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review
J Natl Cancer Inst
(2000) - et al.
Polymorphisms in the DNA repair gene XPD: correlations with risk and age at onset of basal–cell carcinoma
Cancer Epidemiol Biomarkers Prev
(1999) - et al.
Metabolic polymorphisms and susceptibility to cancer—IARC Scientific Publication 148
(1999) Variable penetrance of breast cancer susceptibility genes
Gene–environment interaction and public health
Am J Hum Genet
The new genetics in clinical practice
BMJ
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2017, Environment InternationalCitation Excerpt :In his concept, the exposome encompasses lifetime environmental exposures that include lifestyle factors from the prenatal period onwards (Wild, 2005). From this view, an accurate assessment of a complete exposure history is required to understand the complex interplay with genetic susceptibility, since the majority of genetic alterations will contribute to population disease burden only in the presence of specific environmental exposures (Vineis et al., 2001; Wild, 2005). Rappaport and Smith refined the approach through emphasizing the role of the chemistry in the organism, defining the exposome as the totality of human exposures from all exogenous and endogenous sources in the “internal chemical environment” (Rappaport and Smith, 2010).
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