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Familial risk of early and late onset cancer: nationwide prospective cohort study

BMJ 2012; 345 doi: (Published 20 December 2012) Cite this as: BMJ 2012;345:e8076
  1. E Kharazmi, scientist1,
  2. M Fallah, scientist1,
  3. K Sundquist, professor23,
  4. K Hemminki, professor and head of the division12
  1. 1Division of Molecular Genetic Epidemiology, German Cancer Research Centre, 69120 Heidelberg, Germany
  2. 2Centre for Primary Health Care Research, Lund University, Malmö, Sweden
  3. 3Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California 94305-5705, USA
  1. Correspondence to: E Kharazmi E.Kharazmi{at}
  • Accepted 20 November 2012


Objective To determine whether familial risk of cancer is limited to early onset cases.

Design Nationwide prospective cohort study.

Setting Nationwide Swedish Family-Cancer Database.

Participants All Swedes born after 1931 and their biological parents, totalling >12.2 million individuals, including >1.1 million cases of first primary cancer.

Main outcome measures Familial risks of the concordant cancers by age at diagnosis.

Results The highest familial risk was seen for offspring whose parents were diagnosed at an early age. Familial risks were significantly increased for colorectal, lung, breast, prostate, and urinary bladder cancer and melanoma, skin squamous cell carcinoma, and non-Hodgkin’s lymphoma, even when parents were diagnosed at age 70-79 or 80-89. When parents were diagnosed at more advanced ages (≥90), the risk of concordant cancer in offspring was still significantly increased for skin squamous cell carcinoma (hazard ratio 1.9, 95% confidence interval 1.4 to 2.7), colorectal (1.6, 1.2 to 2.0), breast (1.3, 1.0 to 1.6), and prostate cancer (1.3, 1.1 to 1.6). For offspring with a cancer diagnosed at ages 60-76 whose parents were affected at age <50, familial risks were not significantly increased for nearly all cancers.

Conclusion Though the highest familial risks of cancer are seen in offspring whose parents received a diagnosis of a concordant cancer at earlier ages, increased risks exist even in cancers of advanced ages. Familial cancers might not be early onset in people whose family members were affected at older ages and so familial cancers might have distinct early and late onset components.


  • Contributors: EK and KH planned and designed the study, interpreted the results, and wrote the paper. All authors approved the final manuscript. KS provided the study materials. EK and MF analysed the data. KH is guarantor.

  • Funding: This study was supported by the Swedish Council for Working Life and Social Research and the German Cancer Aid (Deutsche Krebshilfe).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by the Lund regional ethics committee. Consent was not obtained but the presented data are anonymised and there is no risk of identification.

  • Data sharing: No additional data available.

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