Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms: Application to the Genetics of Breast Cancer

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Genetic studies often collect family histories from diagnosed individuals. Some diseases exhibit inter-lineage asymmetry: mothers and their progenitors have higher (or lower) risk than fathers and their progenitors, and descendants of female cases have higher (or lower) risk than descendants of male cases. We describe how certain non-standard genetic mechanisms might underlie that asymmetry and make substantial contributions to disease susceptibility. Besides variants on sex chromosomes, these mechanisms include variants in the mother's genome that influence fetal development and hence later risk, variants in the mitochondria that modulate risk, and susceptibility variants in particular inherited genes whose expression depends on whether the variant came from the mother or the father. Applying our ideas to a study of more than 30,000 families with breast cancer, we found that more maternal grandmothers of cases than paternal grandmothers of cases had breast cancer, giving evidence that such non-standard mechanisms may be important contributors to breast cancer risk.

Vyšlo v časopise: Asymmetry in Family History Implicates Nonstandard Genetic Mechanisms: Application to the Genetics of Breast Cancer. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004174
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004174

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Zdroje

1. National Human Genome Research Institute, National Institutes of Health, “A Catalog of Published Genome-wide Association Studies,” Available:, http://www.genome.gov/GWAStudies, last updated 10 January 2014.

2. ParkJH, GailMH, WeinbergCR, CarrollRJ, ChungCC, et al. (2011) Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants. Proc Natl Acad Sci U S A 108: 18026–18031.

3. WacholderS, HartgeP, PrenticeR, Garcia-ClosasM, FeigelsonHS, et al. (2010) Performance of common genetic variants in breast-cancer risk models. N Engl J Med 362: 986–993.

4. RaskinL, RennertG, GruberSB (2009) FOXP3 germline polymorphisms are not associated with risk of breast cancer. Cancer Genet Cytogenet 190: 40–42.

5. Hill, M.A. Abnormal Development - Fetal Origins Hypothesis. Available: http://embryology.med.unsw.edu.au/embryology/index.php?title=Abnormal_Development_-_Fetal_Origins_Hypothesis, last updated 3 April, 2012.

6. WilcoxAJ, WeinbergCR, LieRT (1998) Distinguishing the effects of maternal and offspring genes through studies of “case-parent triads”. Am J Epidemiol 148: 893–901.

7. LupoPJ, NousomeD, OkcuMF, ChintagumpalaM, ScheurerME (2012) Maternal variation in EPHX1, a xenobiotic metabolism gene, is associated with childhood medulloblastoma: an exploratory case-parent triad study. Pediatr Hematol Oncol 29: 679–685.

8. MichelsKB, TrichopoulosD, RobinsJM, RosnerBA, MansonJE, et al. (1996) Birthweight as a risk factor for breast cancer. Lancet 348: 1542–1546.

9. CanterJA, KallianpurAR, ParlFF, MillikanRC (2005) Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women. Cancer Res 65: 8028–8033.

10. KongA, SteinthorsdottirV, MassonG, ThorleifssonG, SulemP, et al. (2009) Parental origin of sequence variants associated with complex diseases. Nature 462: 868–874.

11. Romano-ZelekhaO, HirshR, BliedenL, GreenM, ShohatT (2001) The risk for congenital heart defects in offspring of individuals with congenital heart defects. Clin Genet 59: 325–329.

12. WeinbergCR, ShoreDL, UmbachDM, SandlerDP (2007) Using risk-based sampling to enrich cohorts for endpoints, genes, and exposures. Am J Epidemiol 166: 447–455.

13. NewschafferCJ, CroenLA, FallinMD, Hertz-PicciottoI, NguyenDV, et al. (2012) Infant siblings and the investigation of autism risk factors. J Neurodev Disord 4: 7.

14. VikanesA, SkjaervenR, GrjibovskiAM, GunnesN, VangenS, et al. (2010) Recurrence of hyperemesis gravidarum across generations: population based cohort study. BMJ 340: c2050.

15. CarterCO, EvansK, CoffeyR, RobertsJA, BuckA, et al. (1982) A three generation family study of cleft lip with or without cleft palate. J Med Genet 19: 246–261.

16. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, et al.. (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45: : 353–361, 361e351–352.

17. National Institute of Environmental Health Sciences, National Institutes of Health, The Sister Study. Available: http://sisterstudy.niehs.nih.gov/English/index1.htm.

18. CampbellMK, FeuerEJ, WunLM (1994) Cohort-specific risks of developing breast cancer to age 85 in Connecticut. Epidemiology 5: 290–296.

19. HoffmanE, SenP, WeinbergC (2001) Within-cluster resampling. Biometrika 88: 1121–1134.

20. LipsitzSR, LairdNM, HarringtonDP (1991) Generalized estimating equations for correlated binary data: Using the odds ratio as a measure of association. Biometrika 78: 153–160.

21. JensenMS, ToftG, ThulstrupAM, HenriksenTB, OlsenJ, et al. (2010) Cryptorchidism concordance in monozygotic and dizygotic twin brothers, full brothers, and half-brothers. Fertil Steril 93: 124–129.

22. CoutoE, HemminkiK (2007) Estimates of heritable and environmental components of familial breast cancer using family history information. Br J Cancer 96: 1740–1742.

23. BevierM, SundquistK, HemminkiK (2012) Risk of breast cancer in families of multiple affected women and men. Breast Cancer Res Treat 132: 723–728.

24. OzanneEM, O'ConnellA, BouzanC, BosinoffP, RourkeT, et al. (2012) Bias in the reporting of family history: implications for clinical care. J Genet Couns 21: 547–556.

25. National Institute of Environmental Health Sciences, National Institutes of Health, The Two Sister Study, Available: http://sisterstudy.niehs.nih.gov/English/2sis.htm.

26. WeinbergCR, WilcoxAJ, LieRT (1998) A log-linear approach to case-parent triad data: Assessing effects of disease genes that act directly or through maternal effects, and may be subject to parental imprinting. Am J Hum Gen 62: 969–978.

27. WilcoxA, WeinbergC, LieR (1998) Distinguishing the effects of maternal and offspring genes through studies of “case-parent triads”. Am J Epid 148: 893–901.