Breast Cancer in Monozygotic Twins

Česká verzia

Authors: A. Hladíková ¹; P. Plevová ¹; E. Macháčková ²
Authors place of work: Oddělení lékařské genetiky, FN Ostrava ¹; Oddělení epidemiologie a genetiky nádorů, Masarykův onkologický ústav, Brno ²
Published in the journal: Klin Onkol 2013; 26(3): 213-217
Category: Case Report

Summary

Summary:
Breast cancer is a multifactorial disease. Twin studies comparing the disease concordance rate in identical twin pairs serve to differentiate the influence of genetic and environmental factors in the disease development.

Aim of the study:
To assess breast cancer risk for an identical twin sister of a patient with breast cancer.

Patients and Methods:
Five monozygotic twin families were examined during 2005– 2011 in which at least one of the monozygotic sisters developed breast cancer.In 4 breast cancer women from 4 families, molecular genetic analysis of BRCA1 and BRCA2 genes was performed.

Results:
The median follow‑up period was 12.6 years (7 to 24 years). No pair of monozygotic sisters was concordant for breast cancer. Familial breast/ ovarian cancer syndrome due to BRCA1 gene mutation was confirmed in one pair. These twins were phenotypically discordant, the first one developing breast cancer at the age of 54 years, her co‑ sister suffering from ovarian cancer at the age of 43 years. In the other 4 non‑BRCA families, breast cancer was diagnosed at the age of 38– 50 years (median 44 years) in one of the sisters; the other twins remain healthy through the follow‑up period.

Conclusion:
We did not observe concordance for breast cancer in 5 pairs of monozygotic twins. Based on results of published studies, the life‑ time breast cancer risk for a healthy identical twin of a breast cancer non‑BRCA woman is around 20– 30 %. Other non‑hereditary risk factors must exist to explain the discordant phenotype. This highlights that environmental factors play an important role in breast cancer development. In case of BRCA‑associated breast cancer, breast cancer risk for the healthy co‑ twin is the same as that for other BRCA mutation carriers, i.e. 45– 85%.

Key words:
breast cancer – BRCA1 gene – BRCA2 gene – monozygotic twins – risk factors

Zdroje

1. Foretová L, Petráková K, Palácová M et al. Genetické testování a prevence hereditárních nádorů v MOÚ – více než desetiletá zkušenost. Klin Onkol 2010; 23(6): 388– 400.

2. Rowell S, Newman B, Boyd J et al. Inherited predisposition to breast and ovarian cancer. Am J Hum Genet 1994; 55(5): 861– 865.

3. Peto J, Collins N, Barfoot R et al: Prevalence of BRCA1 and BRCA2 gene mutations in patients with early‑ onset breast cancer. J Natl Cancer Inst 1999; 91(11): 943– 949.

4. Cui J, Antoniou AC, Dite GS et al. After BRCA1 and BRCA2 – what next? Multifactorial segregation analyses of three‑ generation, population‑based Australian families affected by female breast cancer. Am J Hum Genet 2001; 68(2): 420– 431.

5. Ford D, Easton DF, Peto J et al. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet 1995; 57(6): 1457– 1462.

6. Feigelson HS, Ross RK, Yu MC et al. Genetic susceptibility to cancer from exogenous and endogenous exposures. J Cell Biochem 1996; 25 (Suppl): 15– 22.

7. Bartoňková H, Foretová L, Helmichová E et al. Doporučené zásady péče o nemocné s nádory prsu a vaječníků se zárodečnými mutacemi genů BRCA1 nebo BRCA2. Klin Onkol 2003; 16(1): 28– 34.

8. Bruder CE, Piotrowski A, Gijsbers AA et al. Phenotypically concordant and discordant monozygotic twins display different DNA copy‑ number‑ variation profiles. Am J Hum Genet 2008; 82(3): 763– 771.

9. Machin GA. Some causes of genotypic and phenotypic discordance in monozygotic twin pairs. Am J Med Genet 1996; 61(3): 216– 228.

10. Kato T, Iwamoto K, Kakiuchi C et al. Genetic or epigenetic difference causing discordance between monozygotic twins as a clue to molecular basis of mental disorders. Mol Psychiatry 2005; 10(7): 622– 630.

11. Petronis A, Kennedy JL. Unstable genes – unstable mind? Am J Psychiatry 1995; 152(2): 164– 172.

12. Helderman van den Enden AT, Maaswinkel‑ Mooij PD, Hoogendoorn E et al. Monozygotic twin brothers with the fragile X syndrome: different CGG repeats and different mental capacities. J Med Genet 1999; 36(3): 253– 257.

13. Kaminsky ZA, Tang T, Wang SC et al. DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 2009; 41(2): 240– 245.

14. Ahlbom A, Lichtenstein P, Malmström H et al. Cancer in twins: Genetic and nongenetic familial risk factors. J Natl Cancer Inst 1997; 89(4): 287– 293.

15. Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet 2000; 26(4): 411– 414.

16. Mack TM, Hamilton AS, Press MF et al. Heritable breast cancer in twins. Br J Cancer 2002; 87(3): 294– 300.

17. Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 1998; 62(3): 676– 689.

18. Thompson D, Easton DF. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002; 94(18): 1358– 1365.

19. Antoniou A, Pharoah PD, Narod S et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 2003; 72(5): 1117– 1130.

20. Evans DG, Shenton A, Woodward E et al. Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: Risks of breast/ ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer 2008; 8: 155.

21. Cancer Research.uk [homepage on the Internet]. Breast cancer risk in twins. Available from: http:/ / www.cancerresearchuk.org/ cancer‑ help/ about‑ cancer/ cancer‑ questions/ breast‑ cancer‑ risk‑in‑twins#cancel.

22. Försti A, Luo L, Vorechovsky I et al. Allelic imbalance on chromosomes 13 and 17 mutation analysis of BRCA1 and BRCA2 genes in monozygotic twins concordant for breast cancer. Carcinogenesis 2001; 22(1): 27– 33.

23. Miesfeldt S, Turner BL, Lovell MA et al. A novel BRCA1 mutation in an identical twin pair with similar clinical histories. Cancer Genet Cytogenet 1998; 100(1): 43– 48.

24. Delgado L, Fernandéz G, González A et al. Hereditary breast cancer associated with germline BRCA2 mutation in identical female twins with similar disease expression. Cancer Genet Cytogenet 2002; 133(1): 24– 28.

25. Wistuba II, Tomlison GE, Behrens C et al. Two identical triplet sisters carrying a germline BRCA1 gene mutation acquire very similar breast cancer somatic mutations at multiple other sites throughout the genome. Genes Chromosomes and Cancer 2000; 28(4): 359– 369.

26. Diez O, Brunet J, Sanz E et al. Differences in phenotypic expression of a new BRCA1 mutation in identical twins. Lancet 1997; 350(9079): 713.

27. Lasa A, Ramón y Cajal T, Llort G et al. Copy number variations are not modifiers of phenotypic expression in pair of identical twins carrying a BRCA1 mutation. Breast Cancer Res Treat 2010; 123(3): 901– 905.