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Familial colorectal cancer risk in half siblings and siblings: nationwide cohort study

BMJ 2019; 364 doi: (Published 14 March 2019) Cite this as: BMJ 2019;364:l803
  1. Yu Tian, PhD student1 2 *,
  2. Elham Kharazmi, group coleader1 3 *,
  3. Kristina Sundquist, professor3 4 5,
  4. Jan Sundquist, professor and director3 4 5,
  5. Hermann Brenner, professor and head of division1 6 7,
  6. Mahdi Fallah, group leader1 3
  1. 1Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany
  2. 2Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
  3. 3Center for Primary Health Care Research, Lund University, Malmö, Sweden
  4. 4Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  5. 5Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan
  6. 6Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  7. 7German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
  8. *Contributed equally
  1. Correspondence to: M Fallah m.fallah{at} (or @DrFallah1 on Twitter)
  • Accepted 11 February 2019


Objective To explore the risk of colorectal cancer in family members of patients with colorectal cancer, with an emphasis on subtypes of second degree relatives, especially half siblings, which were lacking in the literature.

Design Ambidirectional cohort study.

Setting Nationwide Swedish Family Cancer Data (record linkage).

Participants All people residing in Sweden and born after 1931, with their biological parents, totalling >16 million individuals (follow-up: 1958-2015); of those with clear genealogy, 173 796 developed colorectal cancer.

Main outcome measures Lifetime (0-79 years) cumulative risk and standardised incidence ratio of colorectal cancer among first degree relatives and second degree relatives.

Results The overall lifetime cumulative risk of colorectal cancer in siblings of patients was 7%, which represents a 1.7-fold (95% confidence interval 1.6 to 1.7; n=2089) increase over the risk in those without any family history of colorectal cancer. A similarly increased lifetime cumulative risk (6%) was found among half siblings (standardised incidence ratio 1.5, 95% confidence interval 1.3 to 1.8; n=140). The risk in people with colorectal cancer in both a parent and a half sibling (standardised incidence ratio 3.6, 2.4 to 5.0; n=32) was close to the risk in those with both an affected parent and an affected sibling (2.7, 2.4 to 3.0; n=396). Family history of colorectal cancer in only one second degree relative other than a half sibling (without any affected first degree relatives), such as a grandparent, uncle, or aunt, showed minor association with the risk of colorectal cancer.

Conclusion Family history of colorectal cancer in half siblings is similarly associated with colorectal cancer risk to that in siblings. The increase in risk of colorectal cancer among people with one affected second degree relative was negligible, except for half siblings, but the risk was substantially increased for a combination of family history in one affected second degree relative and an affected first degree relative (or even another second degree relative). These evidence based findings provide novel information to help to identify people at high risk with a family history of colorectal cancer that can potentially be used for risk adapted screening.


  • Contributors: YT and EK did the analysis, interpreted the results, and wrote the paper with equal contribution. EK and MF planned and designed the study. All authors approved the final manuscript. KS and JS provided the study material. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. MF is the guarantor.

  • Funding: YT has been supported by the China Scholarship Council. The funder had no role in the design, implementation, or interpretation of results of this study.

  • 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 (other than that described above); 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: The study was approved by the Lund Regional Ethics Committee (2012/795). Consent was not obtained, but the presented secondary data are pseudonymised and there is no risk of identification.

  • Data sharing: No additional data available.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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