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Familial Risk for Colorectal Cancers Are Mainly Due to Heritable Causes

Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany and Department of Bioscience, Karolinska Institute, Huddinge, Sweden.

Requests for reprints: Kari Hemminki, Division of Molecular Genetic Epidemiology C050, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany. Phone: 49-62-21/42-1800; Fax: 49-62-21/42-1810. E-mail: K.Hemminki{at}dkfz-heidelberg.de

A family history is an identified risk factor for colorectal cancer (CRC). However, it is not known to what extent the risk is due to environmental or heritable genetic factors. We wanted to examine this question for familial CRC adenocarcinoma based on the nationwide Swedish Family-Cancer Database on 10.3 million individuals whose invasive cancers were followed up to year 2000. Standardized incidence ratios (SIRs) for offspring, siblings, and spouses were calculated based on 5-year age, sex, period (10-year bands), area (county), and socioeconomic status standardized rates. A significant risk was observed in the parent-offspring comparison among different subsites (left-sided and right-sided colon, rectum, and all CRC), the SIRs ranging from 1.74 to 1.84. When husbands were probands, the SIR in wives was 0.92 for colon cancer (left-sided 0.67 and right-sided 1.07), 0.98 for rectal cancer, and 0.96 for CRC. The risks for husbands when wives were probands were quite similar. None of the SIRs between spouses were significant, indicating lack of concordance between spouses that resided together for a minimum of 30 years. The risks between siblings were also increased particularly for cancer in the right-sided colon (SIR 6.89). The effect of shared childhood environmental effects were probed by analyzing the risks by age difference between the siblings. However, the risks were independent of the age difference. Data among spouses and siblings consistently point to the importance of heritable factors in familial CRC.

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