Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers

Janet R Vos, Jan C Oosterwijk, Cora M Aalfs, Matti A. Rookus, Muriel A Adank, Annemarie H. van der Hout, Christi J. van Asperen, Encarna B Gómez Garcia, Arjen R. Mensenkamp, Agnes Jager, Margreet G E M Ausems, Marian J Mourits, Geertruida H de Bock, Hereditary Breast and Ovarian Cancer Research Group Netherlands

Research output: Contribution to journalArticleAcademic

Abstract

BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias.

METHODS: A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history.

RESULTS: The mutation was of paternal origin in 330 (42%, P < 0.001) BRCA1 and 222 (42%, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95% confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95% CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95% CI, 0.25-1.71) and 1.14 (95% CI, 0.42-3.15), respectively.

CONCLUSION: A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear.

IMPACT: There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. ©2016 AACR.

Original languageEnglish
Pages (from-to)1251-8
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 2016

Cite this

Vos, J. R., Oosterwijk, J. C., Aalfs, C. M., Rookus, M. A., Adank, M. A., van der Hout, A. H., ... Hereditary Breast and Ovarian Cancer Research Group Netherlands (2016). Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers. Cancer Epidemiology Biomarkers and Prevention, 25(8), 1251-8. https://doi.org/10.1158/1055-9965.EPI-16-0182
Vos, Janet R ; Oosterwijk, Jan C ; Aalfs, Cora M ; Rookus, Matti A. ; Adank, Muriel A ; van der Hout, Annemarie H. ; van Asperen, Christi J. ; Gómez Garcia, Encarna B ; Mensenkamp, Arjen R. ; Jager, Agnes ; Ausems, Margreet G E M ; Mourits, Marian J ; de Bock, Geertruida H ; Hereditary Breast and Ovarian Cancer Research Group Netherlands. / Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers. In: Cancer Epidemiology Biomarkers and Prevention. 2016 ; Vol. 25, No. 8. pp. 1251-8.
@article{28cdcaf4250f4a4b9a4b3e83e3141468,
title = "Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers",
abstract = "BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias.METHODS: A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history.RESULTS: The mutation was of paternal origin in 330 (42{\%}, P < 0.001) BRCA1 and 222 (42{\%}, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95{\%} confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95{\%} CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95{\%} CI, 0.25-1.71) and 1.14 (95{\%} CI, 0.42-3.15), respectively.CONCLUSION: A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear.IMPACT: There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. {\circledC}2016 AACR.",
keywords = "Journal Article",
author = "Vos, {Janet R} and Oosterwijk, {Jan C} and Aalfs, {Cora M} and Rookus, {Matti A.} and Adank, {Muriel A} and {van der Hout}, {Annemarie H.} and {van Asperen}, {Christi J.} and {G{\'o}mez Garcia}, {Encarna B} and Mensenkamp, {Arjen R.} and Agnes Jager and Ausems, {Margreet G E M} and Mourits, {Marian J} and {de Bock}, {Geertruida H} and {Hereditary Breast and Ovarian Cancer Research Group Netherlands}",
note = "{\circledC}2016 American Association for Cancer Research.",
year = "2016",
month = "8",
doi = "10.1158/1055-9965.EPI-16-0182",
language = "English",
volume = "25",
pages = "1251--8",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "8",

}

Vos, JR, Oosterwijk, JC, Aalfs, CM, Rookus, MA, Adank, MA, van der Hout, AH, van Asperen, CJ, Gómez Garcia, EB, Mensenkamp, AR, Jager, A, Ausems, MGEM, Mourits, MJ, de Bock, GH & Hereditary Breast and Ovarian Cancer Research Group Netherlands 2016, 'Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers' Cancer Epidemiology Biomarkers and Prevention, vol. 25, no. 8, pp. 1251-8. https://doi.org/10.1158/1055-9965.EPI-16-0182

Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers. / Vos, Janet R; Oosterwijk, Jan C; Aalfs, Cora M; Rookus, Matti A.; Adank, Muriel A; van der Hout, Annemarie H.; van Asperen, Christi J.; Gómez Garcia, Encarna B; Mensenkamp, Arjen R.; Jager, Agnes; Ausems, Margreet G E M; Mourits, Marian J; de Bock, Geertruida H; Hereditary Breast and Ovarian Cancer Research Group Netherlands.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 8, 08.2016, p. 1251-8.

Research output: Contribution to journalArticleAcademic

TY - JOUR

T1 - Bias Explains Most of the Parent-of-Origin Effect on Breast Cancer Risk in BRCA1/2 Mutation Carriers

AU - Vos, Janet R

AU - Oosterwijk, Jan C

AU - Aalfs, Cora M

AU - Rookus, Matti A.

AU - Adank, Muriel A

AU - van der Hout, Annemarie H.

AU - van Asperen, Christi J.

AU - Gómez Garcia, Encarna B

AU - Mensenkamp, Arjen R.

AU - Jager, Agnes

AU - Ausems, Margreet G E M

AU - Mourits, Marian J

AU - de Bock, Geertruida H

AU - Hereditary Breast and Ovarian Cancer Research Group Netherlands

N1 - ©2016 American Association for Cancer Research.

PY - 2016/8

Y1 - 2016/8

N2 - BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias.METHODS: A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history.RESULTS: The mutation was of paternal origin in 330 (42%, P < 0.001) BRCA1 and 222 (42%, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95% confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95% CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95% CI, 0.25-1.71) and 1.14 (95% CI, 0.42-3.15), respectively.CONCLUSION: A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear.IMPACT: There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. ©2016 AACR.

AB - BACKGROUND: Paternal transmission of a BRCA mutation has been reported to increase the risk of breast cancer in offspring more than when the mutation is maternally inherited. As this effect might be caused by referral bias, the aim of this study was to assess the parent-of-origin effect of the BRCA1/2 mutation on the breast cancer lifetime risk, when adjusted for referral bias.METHODS: A Dutch national cohort including 1,314 proven BRCA1/2 mutation carriers and covering 54,752 person years. Data were collected by family cancer clinics, via questionnaires and from the national Dutch Cancer Registry. The parent-of-origin effect was assessed using Cox regression analyses, both unadjusted and adjusted for referral bias. Referral bias was operationalized by number of relatives with cancer and by personal cancer history.RESULTS: The mutation was of paternal origin in 330 (42%, P < 0.001) BRCA1 and 222 (42%, P < 0.001) BRCA2 carriers. Paternal origin increased the risk of prevalent breast cancer for BRCA1 [HR, 1.54; 95% confidence interval (CI), 1.19-2.00] and BRCA2 carriers (HR, 1.40; 95% CI, 0.95-2.06). Adjusted for referral bias by several family history factors, these HRs ranged from 1.41 to 1.83 in BRCA1 carriers and 1.27 to 1.62 in BRCA2 carriers. Adjusted for referral bias by personal history, these HRs were 0.66 (95% CI, 0.25-1.71) and 1.14 (95% CI, 0.42-3.15), respectively.CONCLUSION: A parent-of-origin effect is present after correction for referral bias by family history, but correction for the personal cancer history made the effect disappear.IMPACT: There is no conclusive evidence regarding incorporating a BRCA1/2 parent-of-origin effect in breast cancer risk prediction models. Cancer Epidemiol Biomarkers Prev; 25(8); 1251-8. ©2016 AACR.

KW - Journal Article

U2 - 10.1158/1055-9965.EPI-16-0182

DO - 10.1158/1055-9965.EPI-16-0182

M3 - Article

VL - 25

SP - 1251

EP - 1258

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 8

ER -