Skip to main content

Advertisement

Log in

Sex Ratio Distortion in Offspring of Families with BRCA1 or BRCA2 Mutant Alleles: An Ascertainment Bias Phenomenon?

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Background. There has been controversy regarding whether BRCA1 germline mutations favor female births or whether the sex imbalances observed are attributable to ascertainment bias. Our aims were to compare the sex ratios among offspring of BRCA1-positive, BRCA2-positive, and BRCA-negative families undergoing genetic testing in clinical programs, and to determine whether ascertainment bias is responsible for the observed preponderance of female offspring.

Patients and methods. A total of 145 breast and/or ovarian cancer families with mutations in BRCA1 (n = 83) or BRCA2 (n = 62), and 90 families without identifiable mutation were collected for the study from familial cancer clinics in Barcelona, Spain, and Boston, US. Sex ratio was analyzed among all births in the families and offspring of all (tested and obligate) carriers. In order to minimize the effect of family history of cancer, the analysis was also performed among offspring of the most recent generation of mutation-positive carriers who did not have affected children and compared with a control group comprised of the offspring of the most recent adult generation of non-carriers from families with a known mutation.

Results. There was a statistically higher proportion of female births in all groups (BRCA1 59% (95% CI = 57–61%), BRCA2 58% (56–61%), and BRCA-negative 59% (56–61%), respectively). The female preponderance persisted in analyses limited to offspring of BRCA1 and BRCA2 carriers (61% (57–65%), and 62% (58–66%), respectively), with no differences between the two mutation groups. In contrast, the excess of female offspring disappeared when ascertainment or recall biases were minimized, 44% (37–52%), and 39% (26–53%) for BRCA1; 51% (44–58%), and 46% (33–60%) for BRCA2.

Conclusions. Our findings suggest that there is no asymmetry in birth outcomes among BRCA1 or BRCA2 mutations carriers. Rather ascertainment bias in families participating in genetic testing, or in the family history information they provide is likely to account for excess of female offspring previously reported.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. L Zheng S Li TG Boyer WH Lee (2000) ArticleTitleLessons learned from BRCA1 and BRCA2 Oncogene 19 6159–6175 Occurrence Handle10.1038/sj.onc.1203968 Occurrence Handle11156530

    Article  PubMed  Google Scholar 

  2. Statement of the American Society of Human Genetics on genetic testing for breast and ovarian cancer predisposition. Am J Hum Genet 55: i–iv, 1994

  3. Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, Adopted on February 20, 1996. J Clin Oncol 14: 1730–1736; discussion 1737–1740, 1996.

    Google Scholar 

  4. M Hoya Particlede la JM Fernandez A Tosar J Godino A Sanchezde Abajo JA Vidart P Perez-Segura E Diaz-Rubio T Caldes (2003) ArticleTitleAssociation between BRCA1 mutations and ratio of female to male births in offspring of families with breast cancer, ovarian cancer, or both Jama 290 929–931 Occurrence Handle10.1001/jama.290.7.929 Occurrence Handle12928470

    Article  PubMed  Google Scholar 

  5. JP Struewing P Hartge S Wacholder MA Tucker MH Greene (2004) ArticleTitleBRCA1 and sex ratio Eur J Hum Genet 12 663–667 Occurrence Handle10.1038/sj.ejhg.5201210 Occurrence Handle15114373

    Article  PubMed  Google Scholar 

  6. J Feunteun A Chompret A Helbling-Leclerc D Stoppa-Lyonnet M Belotti C Nogues C Bonaiti-Pellie (2004) ArticleTitleSex ratio among the offspring of BRCA mutation carriers Jama 292 687–688 Occurrence Handle10.1001/jama.292.6.687 Occurrence Handle15304464

    Article  PubMed  Google Scholar 

  7. A Agresti C BA (1998) ArticleTitleApproximate is better than “Exact” for interval estimation of binomial proportions Am Stat 52 119–126 Occurrence HandleMR1628435

    MathSciNet  Google Scholar 

  8. A Liede K Metcalfe D Hanna E Hoodfar C Snyder C Durham HT Lynch SA Narod (2000) ArticleTitleEvaluation of the needs of male carriers of mutations in BRCA1 or BRCA2 who have undergone genetic counseling Am J Hum Genet 67 1494–1504 Occurrence Handle10.1086/316907 Occurrence Handle11063672

    Article  PubMed  Google Scholar 

  9. I Gal S Sadetzki R Gershoni-Baruch B Oberman H Carp MZ Papa T Diestelman-Menachem S Eisenberg-Barzilai E Friedman (2004) ArticleTitleOffspring gender ratio and the rate of recurrent spontaneous miscarriages in jewish women at high risk for breast/ovarian cancer Am J Hum Genet 74 1270–1275 Occurrence Handle10.1086/421442 Occurrence Handle15116316

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Judy E. Garber.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balmaña, J., Díez, O., Campos, B. et al. Sex Ratio Distortion in Offspring of Families with BRCA1 or BRCA2 Mutant Alleles: An Ascertainment Bias Phenomenon?. Breast Cancer Res Treat 92, 273–277 (2005). https://doi.org/10.1007/s10549-005-3377-x

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-3377-x

Keywords:

Navigation