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Do discordant cancers share familial susceptibility?

Hemminki, Kari LU ; Sundquist, Jan LU and Brandt, Andreas LU (2012) In European Journal of Cancer 48. p.1200-1207
Abstract
AIMS: Cancer syndromes manifest at many sites albeit with variable penetrance. Genome-wide association (GWA) studies have identified susceptibility loci shared by many types of cancer. Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes. METHODS: Over 1.1million patients in the nation-wide Swedish Family-Cancer Database were analysed for discordant familial cancers covering 33 sites. Standardised incidence ratios (SIRs) were calculated for patients whose family members had a defined cancer compared to those whose family members did not have that cancer. Three independent tests for each pair of cancer sites were done using different family relationships.... (More)
AIMS: Cancer syndromes manifest at many sites albeit with variable penetrance. Genome-wide association (GWA) studies have identified susceptibility loci shared by many types of cancer. Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes. METHODS: Over 1.1million patients in the nation-wide Swedish Family-Cancer Database were analysed for discordant familial cancers covering 33 sites. Standardised incidence ratios (SIRs) were calculated for patients whose family members had a defined cancer compared to those whose family members did not have that cancer. Three independent tests for each pair of cancer sites were done using different family relationships. RESULTS: Lung cancer showed 13 significant discordant associations but most of them were with sites for which smoking is a risk factor. An exception was the clustering of lung cancer and endocrine cancers. Four discordant associations reached a minimal significance level of 5×10(-6): colorectum-endometrium, breast-ovary, breast-prostate and melanoma-squamous cell carcinoma of the skin. The association of melanoma and nervous system cancer reached a minimal significance of 10(-4). Discarding lung cancer, all other associations were based on a single test whereby they were liable to be chance associations. CONCLUSIONS: This study showed the extraordinary requirements for statistical power in study of multiple cancer sites. In addition to the smoking related sites, associations between breast and prostate cancers, melanoma and nervous system tumours and lung and endocrine tumours found strong statistical support. Within the present sample size limits, we found no evidence of an overall susceptibility to cancer. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Cancer
volume
48
pages
1200 - 1207
publisher
IFAC & Elsevier Ltd.
external identifiers
  • wos:000303448200012
  • pmid:22033325
  • scopus:84860497802
ISSN
1879-0852
DOI
10.1016/j.ejca.2011.09.017
language
English
LU publication?
yes
id
e49a28ac-8d98-4e64-bbbb-ca4bbde4fe4d (old id 2200091)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22033325?dopt=Abstract
date added to LUP
2011-11-02 21:41:09
date last changed
2017-10-22 04:55:21
@article{e49a28ac-8d98-4e64-bbbb-ca4bbde4fe4d,
  abstract     = {AIMS: Cancer syndromes manifest at many sites albeit with variable penetrance. Genome-wide association (GWA) studies have identified susceptibility loci shared by many types of cancer. Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes. METHODS: Over 1.1million patients in the nation-wide Swedish Family-Cancer Database were analysed for discordant familial cancers covering 33 sites. Standardised incidence ratios (SIRs) were calculated for patients whose family members had a defined cancer compared to those whose family members did not have that cancer. Three independent tests for each pair of cancer sites were done using different family relationships. RESULTS: Lung cancer showed 13 significant discordant associations but most of them were with sites for which smoking is a risk factor. An exception was the clustering of lung cancer and endocrine cancers. Four discordant associations reached a minimal significance level of 5×10(-6): colorectum-endometrium, breast-ovary, breast-prostate and melanoma-squamous cell carcinoma of the skin. The association of melanoma and nervous system cancer reached a minimal significance of 10(-4). Discarding lung cancer, all other associations were based on a single test whereby they were liable to be chance associations. CONCLUSIONS: This study showed the extraordinary requirements for statistical power in study of multiple cancer sites. In addition to the smoking related sites, associations between breast and prostate cancers, melanoma and nervous system tumours and lung and endocrine tumours found strong statistical support. Within the present sample size limits, we found no evidence of an overall susceptibility to cancer.},
  author       = {Hemminki, Kari and Sundquist, Jan and Brandt, Andreas},
  issn         = {1879-0852},
  language     = {eng},
  pages        = {1200--1207},
  publisher    = {IFAC & Elsevier Ltd.},
  series       = {European Journal of Cancer},
  title        = {Do discordant cancers share familial susceptibility?},
  url          = {http://dx.doi.org/10.1016/j.ejca.2011.09.017},
  volume       = {48},
  year         = {2012},
}