Nationwide registry-based analysis of cancer clustering detects strong familial occurrence of Kaposi sarcoma
Kaasinen, Eevi; Aavikko, Mervi; Vahteristo, Pia; Patama, Toni; Li, Yilong; Saarinen, Silva; Kilpivaara, Outi; Pitkänen, Esa; Knekt, Paul; Laaksonen, Maarit; Artama, Miia; Lehtonen, Rainer; Aaltonen, Lauri; Pukkala, Eero (2013)
Plos ONE 8 1
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Julkaisun pysyvä osoite on
Public Library of Science open access
Many cancer predisposition syndromes are rare or have incomplete penetrance, and traditional epidemiological tools are not well suited for their detection. Here we have used an approach that employs the entire population based data in the Finnish Cancer Registry (FCR) for analyzing familial aggregation of all types of cancer, in order to find evidence for previously unrecognized cancer susceptibility conditions. We performed a systematic clustering of 878,593 patients in FCR based on family name at birth, municipality of birth, and tumor type, diagnosed between years 1952 and 2011. We also estimated the familial occurrence of the tumor types using cluster score that reflects the proportion of patients belonging to the most significant clusters compared to all patients in Finland. The clustering effort identified 25,910 birth name-municipality based clusters representing 183 different tumor types characterized by topography and morphology. We produced information about familial occurrence of hundreds of tumor types, and many of the tumor types with high cluster score represented known cancer syndromes. Unexpectedly, Kaposi sarcoma (KS) also produced a very high score (cluster score 1.91, p-value <0.0001). We verified from population records that many of the KS patients forming the clusters were indeed close relatives, and identified one family with five affected individuals in two generations and several families with two first degree relatives. Our approach is unique in enabling systematic examination of a national epidemiological database to derive evidence of aberrant familial aggregation of all tumor types, both common and rare. It allowed effortless identification of families displaying features of both known as well as potentially novel cancer predisposition conditions, including striking familial aggregation of KS. Further work with high-throughput methods should elucidate the molecular basis of the potentially novel predisposition conditions found in this study.
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