Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer |
| |
| Authors: | Simona Coco Simona Boccardo Marco Mora Vincenzo Fontana Irene Vanni Carlo Genova Angela Alama Sandra Salvi Maria Giovanna Dal Bello Silvia Bonfiglio Erika Rijavec Claudio Sini Giulia Barletta Federica Biello Franca Carli Zita Cavalieri Giovanni Burrafato Luca Longo Francesco Grossi |
| |
| Affiliation: | 1. Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;2. Department of Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;3. Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;4. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;5. Centre for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Milan, Italy;6. UOC Oncologia Medica, IRCCS Cà Granda Foundation, Ospedale Maggiore Policlinico, Milan, Italy;7. Oncologia Medica e CPDO, ASSL di Olbia-ATS Sardegna, Olbia, Italy;8. SCDU Oncologia, AOU Maggiore della Carità, Novara, Italy;1. Department of Surgical Oncology, Breast Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India;2. Breast Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India;3. Department of Pathology, Breast Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India;4. Department of Radiation Oncology, Breast Disease Management Group, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India;1. Department of Breast Oncology, Moffitt Cancer Center, Tampa, FL;2. Breast Care Center, Orlando Health - UF Health Cancer Center, Orlando, FL;3. Present affiliation: Department of Surgery, University Hospitals, Cleveland Medical Center, Cleveland, OH;4. Present affiliation: Tehran University of Medical Sciences, Tehran, Iran;1. Department of Radiology, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China;2. Deepwise AI Lab, Beijing, China;1. Faculty of Biotechnology, October University for Modern Sciences and Arts, Giza, Egypt;2. Department of Surgical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt;3. Department of Pathology, Baheya Centre for Early Detection and Treatment of Breast Cancer, Giza, Egypt;4. Clinical Pathology Department, National Cancer Institute, Cairo University, Cairo, Egypt;5. Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt;6. Breast Surgery Department, Baheya Centre for Early Detection and Treatment of Breast Cancer, Giza, Egypt;7. Center of Material Science Department, Zewail City of Science and Technology, Giza, Egypt;8. Clinical Pathology Department, Baheya Centre for Early Detection and Treatment of Breast Cancer, Giza, Egypt;9. Microbiology Department, College of Medicine, Taif University, Taif, Saudi Arabia;10. Virology Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef, Egypt;1. Houston Methodist Cancer Center, Houston, TX;2. Houston Methodist Research Institute, Houston, TX;1. Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;2. Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Shenzhen Center, Shenzhen, China |
| |
| Abstract: | IntroductionBreast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk.Patients and MethodsThirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups.ResultsEstrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer.ConclusionThe decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation. |
| |
| Keywords: | BRCA1/2 compensatory effect DNA-repair pathway Hormonal asset Lung cancer risk Secondary unrelated cancer |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
