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Do discordant cancers share familial susceptibility?
Kari Hemminki1, Jan Sundquist, Andreas Brandt
1Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Im NeuenheimerFeld 580,Heidelberg, Germany. k.hemminki@dkfz.de
European Journal of Cancer (Oxford, England : 1990)
|October 29, 2011
Summary
This study analyzed over 1.1 million cancer cases to find shared genetic links between different cancer types. While some associations were found, like breast and prostate cancer, no overall cancer susceptibility was identified.
Area of Science:
- Cancer genetics
- Epidemiology
- Population health
Background:
- Cancer syndromes can affect multiple sites with varying penetrance.
- Genome-wide association studies (GWAS) have identified shared cancer susceptibility loci.
- Previous population-level studies of discordant cancers were limited by sample size.
Purpose of the Study:
- To investigate shared genetic susceptibility between discordant cancer types using a large population database.
- To identify specific cancer site pairs with statistically significant familial associations.
Main Methods:
- Analysis of over 1.1 million patients from the Swedish Family-Cancer Database.
- Calculation of standardized incidence ratios (SIRs) for discordant familial cancers across 33 sites.
- Utilized three independent tests per cancer pair, varying family relationships.
Main Results:
- Lung cancer showed 13 significant discordant associations, many related to smoking.
- Notable exceptions included lung cancer with endocrine cancers.
- Significant associations (p < 5x10^-6) found for colorectum-endometrium, breast-ovary, breast-prostate, and melanoma-squamous cell carcinoma of the skin.
Conclusions:
- Studying multiple cancer sites requires substantial statistical power.
- Strong statistical support was found for associations between breast and prostate cancers, melanoma and nervous system tumors, and lung and endocrine tumors.
- No evidence of overall cancer susceptibility was detected within the study's sample size limitations.
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