Albina A Avanesyan1,2, Anna P Sokolenko3,4, Alexandr O Ivantsov5, Maxim A Kleshchev5, Mikhail A Maydin6, Ilya V Bizin5, Grigory A Raskin7, Ksenia V Shelekhova8, Tatiana V Gorodnova9, Alexandr A Bessonov10, Elena I Anisimova11, Olga A Volynshchikova12, Alexandr A Romanko5, Valeria I Ni5, Robert V Broyde1, Oleg B Tkachenko2, Aldon J Whitehead13, Alexandr M Scherbakov2, Evgeny N Imyanitov5,14,15. 1. Department of Endoscopy, City Cancer Center, Saint Petersburg, Russian Federation. 2. Department of Endoscopy, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 3. Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation, annasokolenko@mail.ru. 4. Department of Medical Genetics, St. Petersburg Pediatric Medical University, Saint Petersburg, Russian Federation, annasokolenko@mail.ru. 5. Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 6. Department of Carcinogenesis and Oncogerontology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 7. A.M. Granov Center for Radiology and Surgical Technologies, Saint Petersburg, Russian Federation. 8. Department of Pathology, City Cancer Center, Saint Petersburg, Russian Federation. 9. Department of Oncogynecology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 10. Department of Mammology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 11. Leningrad Regional Oncology Hospital, Saint Petersburg, Russian Federation. 12. Department of Clinical Management and Control, N.N. Petrov Institute of Oncology, Saint Petersburg, Russian Federation. 13. Medicine Internal Medicine Residency Program, The University of Illinois College of Medicine, Chicago, Illinois, USA. 14. Department of Medical Genetics, St. Petersburg Pediatric Medical University, Saint Petersburg, Russian Federation. 15. Department of Oncology, I.I. Mechnikov North-Western Medical University, Saint Petersburg, Russian Federation.
Abstract
INTRODUCTION: There is some evidence suggesting a link between BRCA1/2 germline mutations and increased risk of gastric cancer. METHODS: Endoscopic screening for stomach malignancies was performed in 120 BRCA1 mutation carriers in order to evaluate the probability of detecting the tumor disease. RESULTS: No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I-IV alterations were observed in 26 of 41 (63%) subjects aged >50 years as compared to 29 of 79 (37%) in younger subjects (p = 0.007, χ2 test). One BRCA1 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from BRCA1/2 mutation carriers. Somatic loss of the remaining BRCA1/2 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained BRCA1/2 copy, showed chromosomal instability. CONCLUSION: Taken together, these data justify further studies on the relationships between the BRCA1/2 and gastric cancer.
INTRODUCTION: There is some evidence suggesting a link between BRCA1/2 germline mutations and increased risk of gastric cancer. METHODS: Endoscopic screening for stomach malignancies was performed in 120 BRCA1 mutation carriers in order to evaluate the probability of detecting the tumor disease. RESULTS: No instances of gastric cancer were revealed at the first visit. The analysis of atrophic changes performed by OLGA (Operative Link for Gastritis Assessment) criteria revealed that OLGA stages I-IV alterations were observed in 26 of 41 (63%) subjects aged >50 years as compared to 29 of 79 (37%) in younger subjects (p = 0.007, χ2 test). One BRCA1 mutation carrier developed gastric cancer 4 years after the first visit for endoscopic examination. We performed next-generation sequencing analysis for this tumor and additional 4 archival gastric cancers obtained from BRCA1/2 mutation carriers. Somatic loss of the remaining BRCA1/2 allele was observed in 3 out of 5 tumors analyzed; all of these carcinomas, but none of the malignancies with the retained BRCA1/2 copy, showed chromosomal instability. CONCLUSION: Taken together, these data justify further studies on the relationships between the BRCA1/2 and gastric cancer.