Risks to Relatives

John L Hopper, The University of Melbourne, Victoria, Australia
Gillian S Dite, The University of Melbourne, Victoria, Australia
Graham B Byrnes, The University of Melbourne, Victoria, Australia

Published online: March 2008

DOI: 10.1002/9780470015902.a0005423

Studying risks to relatives can reveal important information on the likely causes of diseases. Even a modest increased risk for relatives of individuals with the disease (affected probands) compared with relatives of individuals without the disease (unaffected probands) cannot exist without there being strong underlying familial risk factors. Studying risks to relatives as a function of the strength of genetic, environmental and cohabitational relationships to the probands can help resolve whether the familial risk factors are likely to have a genetic and/or environmental aetiology, the more so if specific genes and environmental exposures are measured for one or more of the family members. Because only a small proportion of the familial aggregations of common diseases can be explained by known genes and other familial causes, there is scope for greatly expanding our knowledge of disease aetiology through information that can be gained from studying risks to relatives.

Keywords: diseases; familial aggregation; genes; probands; shared environmental factors

Figure 1. Cumulative risk (%) and 95% confidence interval (95% CI) of breast cancer in the sisters, mothers and aunts of the case probands diagnosed with breast cancer before the age of 40 years, 40–49 years and 50–59 years. Cumulative risk=bold line, 95% CI limits=thin line and cumulative risk in the population=dotted line. Note that, in each category of relatives, the risks decrease as the age at onset of the case proband increases. Reproduced from Dite et al. (2003).
Figure 2. Cumulative risk (%) and 95% confidence interval (95% CI) of breast cancer in the sisters, mother and aunts of the case probands who were diagnosed with breast cancer before the age of 40 years and not identified to a carrier of a BRCA1 or BRCA2 mutation. These risks are shown for all relatives of that group, for those with another affected first-degree relative (other than the case proband) and for those without an affected first-degree relative (other than the case proband). Cumulative risk=bold line, 95% CI limits=thin line and cumulative risk in the population=dotted line. Reproduced from Dite et al. (2003).
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 References
    Baglietto L, Jenkins MA, Severi G et al. (2006) Measures of familial aggregation depend on definition of family history: meta-analysis for colorectal cancer. Journal of Clinical Epidemiology 59: 114–124.
    Becker N and Hopper JL (1983) The infectiousness of a disease in a community of households. Biometrika 70: 29–39.
    Bonney GE (1986) Regressive logistic models for familial disease and other binary traits. Biometrics 42: 611–625.
    book Cavalli-Sforza LL and Feldman MW (1981) Cultural Transmission and Evolution: A Quantitative Approach. Princeton, NJ: Princeton University Press.
    Dite G, Jenkins MA, Southey MC et al. (2003) Familial risks, early-onset breast cancer and BRCA1 and BRCA2 germline mutations. Journal of the National Cancer Institute 95(6): 448.
    Elston RC and Stewart J (1971) A general model for the genetic analysis of pedigree data. Human Heredity 21: 523–542.
    Fisher RA (1918) The correlation between relatives on the supposition of Mendelian inheritance. Transactions of the Royal Society of Edinburgh 52: 399–433.
    Goldgar DE, Easton DF, Cannon-Albright LA and Skolnick MH (1994) Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. Journal of the National Cancer Institute 86: 1600–1608.
    Hopper JL, Bishop DT and Easton DF (2005) Genetic epidemiology 6. Population-based family studies in genetic epidemiology. Lancet Series 366: 1397–1406.
    Hopper JL and Carlin JB (1992) Familial aggregation of a disease consequent upon correlation between relatives in a risk factor measured on a continuous scale. American Journal of Epidemiology 136: 1138–1147.
    Hopper JL, Jenkins MA, Macaskill GT and Giles GG (1997) Regressive logistic modelling of familial aggregation for smoking in a population-based sample of nuclear families. Journal of Epidemiology and Biostatistics 2: 45–52.
    Hopper JL, Southey MC, Dite GS et al. (1999) Venter DJ for the Australian Breast Cancer Family Study. Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Cancer Epidemiology, Biomarkers & Prevention 8: 741–747.
    book Lange K (2002) Mathematical and Statistical Methods for Genetic Analysis, chap. 8.9, 2nd edn. New York: Springer.
    Mathews JD (1967) A transmission model for kuru. Lancet 7494: 821–825.
    book Peto J (1980) "Genetic predisposition to cancer". In: Cairns J, Lyon JL and Skolnick M (eds) Banbury Report 4: Cancer Incidence in Defined Populations, pp. 203–213. New York: Cold Spring Harbor Laboratory.
    Pharoah PD, Antoniou A, Bobrow M et al. (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nature Genetics 31: 33–36.
    Risch N (2001) The genetic epidemiology of cancer: interpreting family and twin studies and their implications for molecular genetic approaches. Cancer Epidemiology, Biomarkers & Prevention 10: 733–741.
    Scurrah KJ, Palmer LJ and Burton PR (2000) Variance components analysis for pedigree-based censored survival data using generalized linear mixed models (GLMMs) and Gibbs sampling in BUGS. Genetic Epidemiology 19: 127–148.
    Struewing JP, Hartge P, Wacholder S et al. (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. The New England Journal of Medicine 336: 1401–1408.
    Susser E and Susser M (1987) Indicators and designs in genetic epidemiology: separating heredity and environment. Revue d’ Epidemiologie et de Sante Publique 35: 54–77.
    Susser E and Susser M (1989) Familial aggregation studies. A note on their epidemiologic properties. American Journal of Epidemiology 129: 23–30.
 Further Reading
    book Elston RC, Olson JM and Palmer L (2002) Biostatistical Genetics and Genetic Epidemiology. Chichester: Wiley.
    book Thomas DC (2004) Statistical Methods in Genetic Epidemiology, chap. 5. New York: Oxford University Press.

Related Sub-Topics:

Linkage Analysis | Statistical Methodology in Genetics
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Article Title: Risks to Relatives
 
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Hopper, John L, Dite, Gillian S, and Byrnes, Graham B(Mar 2008) Risks to Relatives. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005423]