The Swedish Family-Cancer Database: Update, Application to Colorectal Cancer and Clinical Relevance

Kari Hemminki,Charlotta Granström,Bowang Chen

doi:10.1186/1897-4287-3-1-7

Abstract

The Swedish Family-Cancer Database has been used for almost 10 years in the study of familial risks at all common sites. In the present paper we describe some main features of version VI of this Database, assembled in 2004. This update included all Swedes born in 1932 and later (offspring) with their biological parents, a total of 10.5 million individuals. Cancer cases were retrieved from the Swedish Cancer Registry from 1958-2002, including over 1.2 million first and multiple primary cancers and in situ tumours. Compared to previous versions, only 6.0% of deceased offspring with a cancer diagnosis lack any parental information. We show one application of the Database in the study of familial risks in colorectal adenocarcinoma, with defined age-group and anatomic site specific analyses. Familial standardized incidence ratios (SIRs) were determined for offspring when parents or sibling were diagnosed with colon or rectal cancer. As a novel finding it was shown that risks for siblings were higher than those for offspring of affected parents. The excess risk was limited to colon cancer and particularly to right-sided colon cancer. The SIRs for colon cancer in age matched populations were 2.58 when parents were probands and 3.81 when siblings were probands; for right-sided colon cancer the SIRs were 3.66 and 7.53, respectively. Thus the familial excess (SIR-1.00) was more than two fold higher for right-sided colon cancer. Colon and rectal cancers appeared to be distinguished between high-penetrant and recessive conditions that only affect the colon, whereas low-penetrant familial effects are shared by the two sites. Epidemiological studies can be used to generate clinical estimates for familial risk, conditioned on numbers of affected family members and their ages of onset. Useful risk estimates have been developed for familial breast and prostate cancers. Reliable risk estimates for other cancers should also be seriously considered for routine clinical recommendations, because practically all cancers show a familial effect and the risks are high for some of the rare neoplasms. The implementation of a unified management plan for familial cancers at large will be a major challenge to the clinical genetic counselling community.

Highlights

The majority of cancers are sporadic and some 1-5% are due to single-gene, dominant traits [1]
In low-penetrant cancers, familial aggregation is present, but Mendelian patterns cannot be ascertained, genetic mechanisms have not been worked out and the only types of available risk estimates are derived from epidemiological studies
For some cancers, screening tests are available and they may be recommendable in familial cases, irrespective of whether the genetic background of the disease is known

Summary

Introduction

The majority of cancers are sporadic and some 1-5% are due to single-gene, dominant traits [1]. The Family-Cancer Database (version V) covered years 1958 to 2000 from the Swedish Cancer Registry and included 11,921 offspring and 80,196 parents with CRCs of adenocarcinoma histology. When parents were not affected, the median diagnostic age for sibling with concordant colon and rectal cancer was 54.3 and 55.9 years, respectively.

Results

Conclusion