Investigation of effects of PALB2 genetic variations on breast cancer predisposition

Year 2020, Volume: 45 Issue: 1, 186 - 194, 31.03.2020

Müge Yüksel Bilen Mehmet Berköz , Ali Erdinç Yalın , Züleyha Çalıkuşu Pelin Eroğlu Ülkü Çömelekoğlu , Serap Yalın

https://doi.org/10.17826/cumj.634598

Cited By: 1

Abstract

Purpose: In this study, the effects of three different single nucleotide polymorphisms (rs249954, rs249935, and rs16940342) of partner and localizer of breast cancer gene 2 (PALB2) on breast cancer predisposition have been investigated.
Materials and Methods: For this purpose, 150 patients diagnosed to have breast cancer and 150 healthy individuals have been included. By using real time polymerase chain reaction (PCR) method isolated deoxyribonucleic acid (DNA) from each case has been investigated for the PALB2 genetic variations.
Results: The distribution of homozygote wild type (AA) and heterozygote (AG) genotypes at rs16940342 polymorphism has been observed to be 44.7% and 55.3% in breast cancer group and 32.7% and 67.3% in control group. The homozygote polymorphic (GG) genotype was not observed in both groups. The discrepancy between the groups in terms of genotype distribution regarding rs16940342 polymorphism has been found statistically significant. However, there was no significant difference in the frequencies of rs249954 and rs249935 polymorphisms comparing both groups.
Conclusion: These results show that rs16940342 polymorphism may be an important determinant in terms of breast cancer predisposition in the Turkish population.

Keywords

Breast cancer, genetic polymorphism, breast cancer gene 2

Supporting Institution

Mersin Üniversitesi BAP Birimi

Project Number

(BAP-SBE BK (MYB) 2010-5 YL)

Thanks

This study was supported by Mersin University Research Foundation (BAP-SBE BK (MYB) 2010-5 YL).

PALB2 genetik varyasyonlarının meme kanseri yatkınlığı üzerindeki etkilerinin araştırılması

Abstract

Amaç: Bu çalışmada, meme kanseri geni partner ve lokalizeri-2’nin (PALB2) üç farklı tek nükleotid polimorfizminin (rs249954, rs249935 ve rs16940342) meme kanseri predispozisyonu üzerindeki etkileri araştırılmıştır.
Gereç ve Yöntem: Bu amaçla, çalışmamıza meme kanseri tanısı almış 150 hasta ve 150 sağlıklı birey dahil edilmiştir. Gerçek zamanlı polimeraz zincir reaksiyonu (PCR) yöntemi kullanılarak, her bir vakadan izole edilmiş deoksiribonükleik asit (DNA), PALB2 genetik varyasyonları için araştırılmıştır.
Bulgular: rs16940342 polimorfizminin homozigot yabanıl tip (AA) ve heterozigot (AG) genotip dağılımı meme kanseri grubunda sırasıyla % 44,7 ve % 55,3, kontrol grubunda ise % 32,7 ve % 67,3 olarak bulunmuştur. Her iki grupta da homozigot polimorfik (GG) genotip gözlenmemiştir. rs16940342 polimorfizmi için gruplar arasındaki genotip dağılımı açısından fark istatistiksel olarak anlamlı bulunmuştur. Bununla birlikte, her iki grup karşılaştırıldığında rs249954 ve rs249935 polimorfizmlerinin sıklığı bakımından istatistiksel olarak anlamlı bir fark bulunamamıştır.
Sonuç: Bu sonuçlar rs16940342 polimorfizminin Türk popülasyonunda meme kanseri yatkınlığı açısından önemli bir belirleyici rol üstlenebileceğini göstermektedir.

Keywords

Meme kanseri, genetik polimorfizm, PALB2

Project Number

(BAP-SBE BK (MYB) 2010-5 YL)

References

• 1. Tyagi NK, Dhesy-Thind S. Clinical practice guidelines in breast cancer. Curr Oncol. 2018; 25: 151-60.
• 2. Lammert J, Grill S, Kiechle M. Modifiable Lifestyle Factors: Opportunities for (Hereditary) Breast Cancer Prevention - a Narrative Review. Breast Care (Basel). 2018;13:109-14.
• 3. Soguel L, Durocher F, Tchernof A, Diorio C. Adiposity, breast density, and breast cancer risk: epidemiological and biological considerations. Eur J Cancer Prev. 2017;26:511-20.
• 4. Dandamudi A, Tommie J, Nommsen-Rivers L, Couch S. Dietary Patterns and Breast Cancer Risk: A Systematic Review. Anticancer Res. 2018;38:3209-22.
• 5. Shrivastava SR, Shrivastava PS, Ramasamy J. Exploring the role of dietary factors in the development of breast cancer. J Cancer Res Ther. 2016;12:493-7.
• 6. Croce CM. Oncogenes and cancer. N Engl J Med. 2008;385:503-11.
• 7. Peairs KS, Choi Y, Stewart RW, Sateia HF. Screening for breast cancer. Semin Oncol. 2017;44:60-72.
• 8. Zhang W, Luo J, Chen F, Yang F, Song W, Zhu A et al. BRCA1 regulates PIG3-mediated apoptosis in a p53-dependent manner. Oncotarget. 2015;6:7608-18.
• 9. Gómez-Flores-Ramos L, Álvarez-Gómez RM, Villarreal-Garza C, Wegman-Ostrosky T, Mohar A. Breast cancer genetics in young women: What do we know? Mutat Res. 2017;774:33-45.
• 10. Paul A, Paul S. The breast cancer susceptibility genes (BRCA) in breast and ovarian cancers. Front Biosci (Landmark Ed). 2014;19:605-18.
• Hernandez-Aya LF, Gonzalez-Angulo AM. Targeting the phosphatidylinositol 3-kinase signaling pathway in breast cancer. Oncologist. 2011;16:404-14.
• 12. Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet. 2007;39:162-4.
• 13. Zhang F, Ma J, Wu J, Ye L, Cai H, Xia B et al. PALB2 links BRCA1 and BRCA2 in the DNA-damage response. Curr Biol. 2009;19:524-9.
• 14. Xia B, Sheng Q, Nakanishi K, Ohashi A. Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell. 2007;22:719-29.
• 15. Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet. 2007;39:165-7.
• 16. Cao AY, Huang J, Hu Z, Li WF, Ma ZL, Tang LL et al. The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat. 2009;114:457-62.
• 17. Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature. 2007;446:316-9.
• 18. U.S. National Library of Medicine. National Center for Biotechnology Information. dbSNP Short Genetic Variations. https://www.ncbi.nlm.nih.gov/snp/rs249954 (accessed Feb 2012).
• 19. U.S. National Library of Medicine. National Center for Biotechnology Information. dbSNP Short Genetic Variations. https://www.ncbi.nlm.nih.gov/snp/rs249935 (accessed Feb 2012).
• 20. U.S. National Library of Medicine. National Center for Biotechnology Information. dbSNP Short Genetic Variations. https://www.ncbi.nlm.nih.gov/snp/rs249954 (accessed Feb 2012).
• 21. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. Cancer J Clin. 2011;61:69-70.
• 22. Kamińska M, Ciszewski T, Łopacka-Szatan K, Miotła P, Starosławska E. Breast cancer risk factors. Prz Menopauzalny. 2015;14:196-202.
• 23. van Veldhoven K, Rahman S, Vineis P. Epigenetics and epidemiology: models of study and examples. Cancer Treat Res. 2014;159:241-55.
• 24. Nasir A, Shackelford RE, Anwar F. Genetic risk of breast cancer. Minerva Endocrinol. 2009;34:295-310.
• 25. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374-403.
• Chen CF, Li S, Chen Y, Chen PL, Sharp ZD, Lee WH. The nuclear localization sequences of the BRCA1 protein interact with the importin-alpha subunit of the nuclear transport signal receptor. J Biol Chem. 1996;271:32863-8.
• 27. Santen R, Cavalieri E, Rogan E, Russo J, Guttenplan J, Ingle J et al. Estrogen mediation of breast tumor formation involves estrogen receptor-dependent, as well as independent, genotoxic effects. Ann N Y Acad Sci. 2009;1155:132-40.
• 28. Dansonka-Mieszkowska A, Kluska A, Moes J, Dabrowska M, Nowakowska D, Niwinska A et al. A novel germline PALB2 deletion in Polish breast and ovarian cancer patients. BMC Med Genet. 2010;11:20-8.
• 29. Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G et al. Analysis of PALB2/FANCN-associated breast cancer families. Proc Natl Acad Sci USA. 2007;104:6788-93.
• 30. Foulkes WD, Ghadirian P, Akbari MR, Hamel N, Giroux S, Sabbaghian N et al. Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French- Canadian women. Breast Cancer Res. 2007;9:83-9.