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Population-based relative risks for specific family history constellations of breast cancer

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Abstract

Purpose

Using a large resource linking genealogy with decades of cancer data, a non-traditional approach was used to estimate individualized risk for breast cancer (BC) based on specific family history extending to first cousins, providing a clearer picture of the contribution of various aspects of both close and distant combinations of affected relatives.

Methods

RRs for BC were estimated in 640,366 females for a representative set of breast cancer family history constellations that included number of first- (FDR), second-(SDR), and third-degree relatives (TDR), maternal and paternal relatives, and age at earliest diagnosis in a relative.

Results

RRs for first-degree relatives of BC cases ranged from 1.61 (= 1 FDR affected, CI 1.56, 1.67) to 5.00 (≥ 4 FDRs affected, CI 3.35, 7.18). RRs for second-degree relatives of probands with 0 affected FDRs ranged from 1.04 (= 1 SDR affected, CI 1.00, 1.08) to 1.71 (≥ 4 SDRs affected, CI 1.26, 2.27) and for second-degree relatives of probands with exactly 1 FDR from 1.54 (0 SDRs affected, CI 1.47, 1.61) to 4.78 (≥ 5 SDRs; CI 2.47, 8.35). RRs for third-degree relatives with no closer relatives affected were significantly elevated over population risk for probands with ≥ 5 affected TDRs RR = 1.32, CI 1.11, 1.57).

Conclusions

The majority of females in the Utah resource had a positive family history of BC in FDRs to TDRs. Presence of any number of affected FDRs or SDRs significantly increased risk for BC over population risk; and more than four TDRs, even with no affected FDRs or SDRs, significantly increased risk over population risk. Risk prediction derived from the specific and extended family history constellation of affected relatives allows identification of females at increased risk even when they do not have a conventionally defined high-risk family; these risks could be a powerful, efficient tool to individualize cancer screening and prevention.

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Abbreviations

FDR:

first-degree relative

RR:

relative risk

SDR:

second-degree relative

SEER:

Surveillance, Epidemiology, and End Results

TDR:

third-degree relative

UCR:

Utah Cancer Registry

UPDB:

Utah Population Database

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Acknowledgments

Research was supported by the Utah Cancer Registry, which is funded by Contract No. HHSN261201000026C from the National Cancer Institute’s SEER Program with additional support from the Utah State Department of Health and the University of Utah. Partial support for all datasets within the Utah population database (UPDB) was provided by Huntsman Cancer Institute, Huntsman Cancer Foundation, University of Utah, and the Huntsman Cancer Institute’s shared resources (UPDB and Genetic Counseling Shared Resource) Cancer Center Support grant, P30 CA42014, from National Cancer Institute. LACA received support from the George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, and the Huntsman Cancer Foundation. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA042014. These funding bodies played no role in the design of the study nor in collection, analysis, and interpretation of data.

Author information

Authors and Affiliations

  1. Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA

    Frederick S. Albright

  2. Huntsman Cancer Institute, University of Utah Health Sciences Center, 391 Chipeta Way, Suite D, Salt Lake City, UT, 84108, USA

    Wendy Kohlmann, Saundra S. Buys, Cindy B. Matsen, Kimberly A. Kaphingst & Lisa A. Cannon-Albright

  3. Department of Surgery, University of Utah School of Medicine, Salt Lake City, USA

    Leigh Neumayer

  4. Department of Surgery, University of Arizona College of Medicine, Tucson, AZ, USA

    Leigh Neumayer

  5. Division of Oncology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

    Saundra S. Buys & Cindy B. Matsen

  6. Department of Communication, University of Utah College of Humanities, Salt Lake City, UT, USA

    Kimberly A. Kaphingst

  7. Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA

    Lisa A. Cannon-Albright

  8. George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA

    Lisa A. Cannon-Albright

Authors
  1. Frederick S. Albright
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  2. Wendy Kohlmann
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  4. Saundra S. Buys
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  7. Lisa A. Cannon-Albright
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Contributions

FSA contributed to study design, analyzed and interpreted data, and was a major contributor in writing. WK, LN, SSB, CBM, and KAK were major contributors in writing and consideration of clinical implications. LACA conceived of the study design and developed the analysis methods and was a major contributor in writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lisa A. Cannon-Albright.

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Conflict of interest

The authors declare no potential conflicts of interest or competing interests.

Availability of data and materials

The datasets generated and analyzed during the current study are not publicly available. The Utah Resource for Genetic and Epidemiologic Research (RGE) and Institutional Review Boards (IRB) administer access to the UPDB resource (https://uofuhealth.utah.edu/huntsman/utah-population-database) through a review process.

Consent for publication

Not applicable.

Ethics approval and consent to participate

Approval for this research was received from the University of Utah School of Medicine Institutional Review Board and from the Resource for Genetic and Epidemiologic Research which oversees the UPDB.

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Albright, F.S., Kohlmann, W., Neumayer, L. et al. Population-based relative risks for specific family history constellations of breast cancer. Cancer Causes Control 30, 581–590 (2019). https://doi.org/10.1007/s10552-019-01171-5

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  • DOI: https://doi.org/10.1007/s10552-019-01171-5

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