BRCA1/2 normal meme kanserli kadınlarda genotip-fenotip ilişkisinin araştırılması: Türkiye'den tek merkez deneyimi

Year 2021, Volume: 12 Issue: 3, 349 - 356, 29.09.2021

Neslihan Duzkale , Aysun Gökce , Tülay Eren , Gökşen İnanç İmamoğlu , Mustafa Altınbaş

https://doi.org/10.18663/tjcl.948240

Abstract

Amaç: Meme kanserlerinin yaklaşık %10'unun kalıtsal olduğu ve bunların yaklaşık %20'sinden BRCA1/2 genlerinin sorumlu olduğu bilinmektedir. Yapılan araştırmalar, meme kanserinde BRCA1/2 dışındaki birçok genin mutasyonlarının da yatkınlığa neden olduğunu göstermiştir. Bu çalışmada meme kanserli Türk kadınlarda diğer kanser yatkınlık genlerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Bu retrospektif çalışmaya Ankara Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi Genetik Bölümü'nde 2016-2021 yılları arasında değerlendirilen 66 kadın hasta dahil edildi. Hastaların kansere yatkınlık genleri, yeni nesil dizileme tekniği (NGS) kullanılarak incelendi.
Bulgular: Hastaların ortalama tanı yaşı 43 ± 8.0 idi. Genetik analiz ile 66 hastanın 9'unda (%13,63) nedensel gen tespit edildi. Bu genler ATM (%13), CHEK2 (%36), FANCC (%13), MUTYH (%13) ve PALB2'dir (%25). Nedensel varyantı olan hastalar ve diğerleri gruplandırılarak tanı yaşı, tümör lokalizasyonu, tümörün histopatolojik tipi, östrojen/progesteron reseptör durumu, cerbb2, evre, tanı anındaki metastaz ve kanserli akraba sayısı gibi parametreler açısından karşılaştırıldı. Gruplar arasında istatistiksel bir ilişki bulunamadı.
Sonuç: Bu çalışmada meme kanserli Türk kadınlarında BRCA1/2 dışındaki kansere yatkınlık genlerinin nedensel varyantlarının saptanma oranı %13,63 olarak belirlendi. Kanserli bireylerde NGS ile çoklu gen testlerinin yapılması, taşıyıcı bireylerin doğru tanı ve uygun tedavi almalarını ve gerekli taramalara yönlendirilmelerini sağlayacaktır.

Keywords

Meme kanseri , BRCA1/2 , kalıtsal kanser yatkınlık genleri , yeni nesil dizileme , çoklu gen paneli

Investigation of genotype-phenotype relationship in women with BRCA1/2 normal breast cancer: A single-center experience from Turkey

Abstract

Aim: It is known that approximately 10% of breast cancers are hereditary, and BRCA1/2 genes are responsible for
approximately 20% of these. Studies have shown that mutations of many genes other than BRCA1/2 in breast cancer also
cause this predisposition. In this study, it was aimed to investigate other causative cancer susceptibility genes in women
with breast cancer.
Material and Methods: In this retrospective study, 66 female patients who were evaluated in Ankara Dışkapı Yıldırım
Beyazıt Training and Research Hospital Genetics Department between 2016-2020 were included. Cancer susceptibility
genes of the patients were examined using next-generation sequencing technique (NGS).
Results: Mean age at diagnosis of the patients was 43 ± 8.0. By genetic analysis, causative genes were identified in 9
(13.63%) of 66 patients. These genes are ATM (%11), BRIP1 (%11), CHEK2 (%34), FANCC (%11), MUTYH (%11) and PALB2
(%22). Patients with a causal variant and others were grouped, and compared in terms of parameters such as age at
diagnosis, tumor localization, histopathological type of tumor, estrogen/progesterone receptor status, c-erbB2, stage,
metastasis at diagnosis, and number of relatives with cancer. No statistical relationship was found between the groups.
Conclusion: This study determined the rate of detection of causal variants of cancer susceptibility genes other than
BRCA1/2 in women with breast cancer who applied to the medical genetics department as 13.63%. Performing multiple
gene tests with the NGS in cancer individuals will allow carrier individuals to receive correct diagnosis and appropriate
treatment and to be directed to necessary screenings.

Keywords

Breast cancer , BRCA1/2 , hereditary cancer susceptibility genes , next generation sequencing , multi-gene panel

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