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Cancer of Unknown Primary pp 5–25Cite as

Epidemiology, Risk Factors, and Survival in CUP: Pointers to Disease Mechanisms

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Abstract

Epidemiology on cancer of unknown primary (CUP) has been a neglected area. Much of the related literature was based on hospital series which did not capture the dismal survival rates for CUP, now established in population-based series. The recent data also show differential survival by the location of metastases. Even though the incidence of CUP has declined in many countries, it still ranks as one of the leading cancer deaths. Immigrant studies from Sweden showed incidence rates less than half of the Swedish rates for some non-European immigrant populations, suggesting that the rates are also low in immigrants’ countries of origin. Among risk factors, heavy smoking conveys a risk of 3.7 and any level of smoking increased the risk for CUP with respiratory system metastases to 4.9. Alcohol consumption, body mass index, waist circumference, diabetes, and low educational level or socioeconomic status may be other risk factors. Familial risk is another established risk factor with important implications for disease mechanisms. CUP associated with many cancers in family members, including cancers of the lung, liver, and kidney. The cause of death for many CUP patients was apparently the metastatic location which the death registrar judged to be fatal. Curiously, cancers in this location were in excess in family members, which lead us to speculate that the cause of death in some CUP patients pointed to the tissue of origin. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These data, together with the fact that smoking caused preferably CUP with lung metastases, suggest that some CUP cases are phenotypically modified primary cancers, rather than cancers of unknown primaries.

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Acknowledgments

Jan Sundquist, Kristina Sundquist, Jianguang Ji, Hao Liu, Akseli Hemminki, Matias Riihimäki, Melanie Bevier, and Xiaochen Shu contributed to various stages of the reported studies.

Financial Support

KH received support to these studies by Deutsche Krebshilfe and the Swedish Council for Working Life and Social Research.

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Authors and Affiliations

  1. Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Kari Hemminki

  2. Lund University, Malmö, Sweden

    Kari Hemminki

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Correspondence to Kari Hemminki .

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Editors and Affiliations

  1. German Cancer Research Center (DKFZ) and University of Heidelberg, Clinical Cooperation Unit Molecular, Hematology/Oncology, Heidelberg, Germany

    Alwin Krämer

  2. German Cancer Research Center (DKFZ) and University of Heidelberg, Clinical Cooperation Unit Molecular, Hematology/Oncology, Heidelberg, Germany

    Harald Löffler

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Hemminki, K. (2016). Epidemiology, Risk Factors, and Survival in CUP: Pointers to Disease Mechanisms. In: Krämer, A., Löffler, H. (eds) Cancer of Unknown Primary. Springer, Cham. https://doi.org/10.1007/978-3-319-22581-4_2

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  • DOI: https://doi.org/10.1007/978-3-319-22581-4_2

  • Publisher Name: Springer, Cham

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  • Online ISBN: 978-3-319-22581-4

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