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- Hemminki, Kari, et al.
(författare)
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Do discordant cancers share familial susceptibility?
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 48, s. 1200-1207
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Roudgari, Hassan, et al.
(författare)
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Prostate cancer risk assessment model: a scoring model based on the Swedish Family-Cancer Database
- 2012
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:5, s. 345-352
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Tidskriftsartikel (refereegranskat)abstract
- Background Many prostate cancer (PC) risk assessment models have been developed, however almost none include familial history. Aim To produce a risk assessment model for PC based on familial background of related cancers. Method 976 859 independent index men aged >= 30 in year 1998 and their family members in the Swedish Family-Cancer Database (FCD2010) were randomly divided into development (60%) and validation (40%) datasets (follow-up 10 years). The HR from Cox model was used to extrapolate risk scores. Results Specified scores were: for PC in situ at age <60 years in index man, 5; for PC at age <60 years in each first-degree relative (FDR), 15; for PC at age >= 60 years in each FDR, 10; for PC at age <60 years in each second-degree relative, 5; for breast cancer in each FDR, 2; for oesophageal carcinoma in situ in index man, 2; and for oesophagus cancer in each FDR, 2. Based on the findings, if the milestone age for a PC screening programme was 60 years or more, the recommended starting age for the men with the score-group 6-10 would be 54 years; score-group 11-15, 52 years; score-group 16-20, 50 years; score-group 21-25, 44 years; and for the score-group 26+ it should start before age 40. The concordance index in development and validation sets was 0.885 (95% CI 0.883 to 0.888). No significant difference was found between curves from development and validation datasets (internally validated using twofold validation and bootstrapping). Conclusion Familial history of relevant malignancies can be used as risk factors to estimate a man's prior risk of developing PC. The prostate cancer risk assessment model could satisfactorily assess risk of developing prostate cancer.
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