Genetic Disorders Requiring Risk-Reducing Surgical Management in Our Gynecological Oncology Practice

Yıl 2022, Cilt: 31 Sayı: 2, 132 - 146, 30.06.2022

Ferah Kazancı , Feride İffet Şahin

https://doi.org/10.17827/aktd.1059207

Öz

Cancer occurs as a result of the mutations in genes that are responsible for cell development and DNA integrity. Mutations can occur in germ cells (germline) (GLM) as well as others (somatic) (SM). GLM are responsible for 5-10% of cancers. Early detection of GLMs is critical for identifying at-risk individuals, following up, and designing risk-reducing procedures. Furthermore, the detection of SM in tumor tissue has recently been used to determine the necessity for extra adjuvant and targeted therapy. Although familial clustering is observed in 10-30% of ovarian (OC) and breast (BC) cancer cases. GLM in the BRCA1/2, which cause DNA repair deficiencies, are responsible for 65-85% of genetic anomalies in hereditary OC. Risk-reducing mastectomy (RRM) reduces the risk of BC by about % 90-95 in cases with pathogenic mutations (PMs) in the BRCA1/2 genes, while risk-reducing salpingo-oophorectomy (RRSO) reduces the incidence of BC (%50 ) and OC(%70-96 ), as well as a decrease in overall cancer-specific mortality. Except for BRCA1/2, OC is caused by PMs in genes like RAD51C, RAD51D and BRIP1, which affect DNA repair process. RRSO is indicated among carriers of PMs in these genes. Lynch syndrome (LS) is associated with a higher risk of colorectal and endometrial cancer. After completing their fertility, hysterectomy and bilateral RRSO are recommended for carriers of PMs in the MLH1, MSH2, and MSH6 genes. Based on the most recent guidelines, our goal in this review is to highlight the genetic alterations that necessitate risk-reducing prophylactic surgical procedures, which are becoming more common in our gynecological oncology practice. 

Anahtar Kelimeler

Hereditary cancer syndrome, Risk reducing surgery, BRCA1/2, RAD51 genes, PALB2, BIRP1

Destekleyen Kurum

No

Proje Numarası

No

Teşekkür

None

Jinekolojik Onkoloji Pratiğimizde Risk Azaltıcı Cerrahi Yönetimi Gerektiren Genetik Değişiklikler

Öz

Kanser, fonksiyonu hücre büyümesi ve DNA’nın bütünlüğünü koruma olan genlerdeki mutasyonlar sonucu gelişir. Mutasyonlar, germ hücrelerinde(germline)(GLM) ve diğer hücrelerde (somatik)(SM) olabilir. Kanserlerin %5-10’undan germline mutasyonlar sorumludur. Erken dönemde GLM’ların tespit edilmesi; risk altındaki bireylerin belirlenmesi, takibinin yapılması ve risk azaltıcı koruyucu stratejilerin geliştirilmesi açısından önemlidir. Ayrıca son zamanlarda tümör dokusunda SM’ların tespiti, hedefe yönelik ve adjuvan tedaviyi düzenlemede rehber olmaktadır. Over ve meme kanserlerinin yaklaşık %10-30’u ailesel kümelenme göstermekle birlikte vakaların sadece %5-10’u kalıtsaldır. Özellikle, kalıtsal over kanserlerinin yaklaşık %65-85’ini DNA onarım kusurlarına neden olan BRCA1/2 genlerinde GLM’lar sonucu oluşmaktadır. BRCA1/2 genlerinde patojenik mutasyonu olan bireyler için risk azaltıcı mastektomi (RRM) meme kanseri riskini %90-95 oranında azaltırken, salpingo-ooferektomi (RRSO) ile meme ( %50), over ve fallop tüpü kanseri insidansı da ( %70-96) azalmaktadır. Ayrıca RRSO, kansere özgü genel mortaliteyi azaltmakla ve over kanserini önlemede en etkili seçenek olarak kabul edilmektedir. BRCA1/2 dışında homolog rekombinasyon yolu DNA tamirinde rol oynayan RAD51C, RAD51D ve BRIP1 genlerdeki patojenik mutasyonlar over kanserinde rol oynamaktadır. RAD51C, RAD51D ve BRIP1, genlerinin patojenik mutasyon taşıyıcılarında rehberler, RRSO’i önermektedir. Lynch sendromu (LS), kolorektal ve endometriyal kanser gelişme riskinde artış ile karakterize otozomal dominant bir hastalıktır. LS’da endometrium ve over kanseri risk artışı en fazla olan MLH1, MSH2 ve MSH6 genlerinde patojenik mutasyon taşıyıcılarında fertilitesini tamamladıktan sonra risk azaltıcı cerrahi olarak histerektomi ve RRSO önerilmektedir. Bu derlemede amacımız, jinekolojik onkoloji pratiğimizde son zamanlarda kullanımı gittikçe artan risk azaltıcı profilaktik cerrahi uygulamaları gerektiren genetik hastalıkları son rehberler eşliğinde özetlemektir. 

Anahtar Kelimeler

BRCA1/2, PALB2, Kalıtsal kanser sendromu, Risk azaltıcı cerrahi, BRCA1/2, RAD51 genleri, PALB2, BIRP1.

Proje Numarası

No

Kaynakça

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