Combined associations of genetic and environmental risk factors: implications for prevention of breast cancer.
Genome-wide association studies (GWAS) have identified hundreds of genetic susceptibility loci for cancers and other complex diseases. However, the public health and clinical relevance of these discoveries is unclear. Evaluating the combined associations of genetic and environmental risk factors, particularly those that can be modified, will be critical in assessing the utility of genetic information for risk stratified prevention. In this commentary, using breast cancer as a model, we show that genetic information in combination with other risk factors can provide levels of risk stratification that could be useful for individual decision-making or population-based prevention programs. Our projections are theoretical and rely on a number of assumptions, including multiplicative models for the combined associations of the different risk factors, which need confirmation. Thus, analyses of epidemiological studies with high-quality risk factor information, as well as prevention trials, are needed to empirically assess the impact of genetics in risk stratified prevention.
Division of Genetics and Epidemiology and Breakthrough Breast Cancer Centre, Institute of Cancer Research, Sutton, Surrey, UK (MGC, NBG); Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (NC).
Montserrat
M
Garcia-Closas
Division of Genetics and Epidemiology and Breakthrough Breast Cancer Centre, Institute of Cancer Research, Sutton, Surrey, UK (MGC, NBG); Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (NC).
Necdet Burak
NB
Gunsoy
Division of Genetics and Epidemiology and Breakthrough Breast Cancer Centre, Institute of Cancer Research, Sutton, Surrey, UK (MGC, NBG); Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD (NC). chattern@mail.nih.gov.
Nilanjan
N
Chatterjee
D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control*; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage*; D006113:United Kingdom / Q000453:epidemiology
D016588:Anticarcinogenic Agents; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators