Cancer Research and Treatment

Original Articles

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test: Hee-Chul Shin, Han-Byoel Lee, Tae-Kyung Yoo, Eun-Shin Lee, Ryong Nam Kim, Boyoung Park, Kyong-Ah Yoon, Charny Park, Eun Sook Lee, Hyeong-Gon Moon, Dong-Young Noh, Sun-Young Kong, Wonshik Han; Cancer Res Treat. 2020;52(3):697-713. Published online February 4, 2020; DOI: https://doi.org/10.4143/crt.2019.559

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Purpose
Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).
Materials and Methods
A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.
Results
Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.
Conclusion
NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.

Citations

Citations to this article as recorded by

Risk-Reducing Mastectomy in BRCA1/2 and Other High-Risk Gene Carriers: Current Evidence and Practical Guidance
Jun-Hee Lee, Jai Min Ryu, Ji Soo Park, Joo Heung Kim, Chihwan David Cha, Kyung Jin Eoh, Yaewon Yang, Bom-Yi Lee, Sang-Ah Han, Sung-Won Kim
Journal of Breast Cancer.2026; 29(1): 1. CrossRef
Pathogenicity Prediction of Missense Variations in Hereditary Cancer Genes
Cemaliye B. Akyerli, Gizel Gerdan, Alper Bülbül, Hilal Keskin-Karakoyun, Şirin K. Yüksel, Emel Timucin
International Journal of Molecular Sciences.2026; 27(5): 2453. CrossRef
Comprehensive germline and somatic profiling of high-risk Thai breast cancer via next-generation sequencing
Kornyok Kamdee, Ekkapong Roothumnong, Wanna Thongnoppakhun, Krittiya Korphaisarn, Panee Nakthong, Peerawat Dungort, Chutima Meesamarnpong, Supakit Wiboontanasarn, Warisara Tansa-nga, Kittiporn Punuch, Khontawan Pongsuktavorn, Warunya Tititumjariya, Chitta
Scientific Reports.2025;[Epub] CrossRef
Next-generation sequencing in cancer diagnosis and treatment: clinical applications and future directions
Nima Ghoreyshi, Reza Heidari, Arezoo Farhadi, Mohsen Chamanara, Nastaran Farahani, Mahmood Vahidi, Javad Behroozi
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Medicina.2025; 61(6): 1029. CrossRef
Genetic landscape of Pakistani familial breast cancer patients using multigene panel testing
Muhammad Usman Rashid, Noor Muhammad, Shumaila Arif, Humaira Naeemi, Ute Hamann
International Journal of Cancer.2025; 157(10): 2081. CrossRef
NGS-DRIVEN MUTATION PROFILING IN BREAST CANCER: BRIDGING THE GAP BETWEEN REAL-WORLD DATA AND PERSONALIZED THERAPY
S MALIK, A MALIK, J ISLAM, A ZAHID, J IQBAL, M MARVI, Q ALI, A FATIMA
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Hyunwoo Lee, Yoon Ah Cho, Deok Geun Kim, Eun Yoon Cho
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Identification of pathogenic germline variants in a large Chinese lung cancer cohort by clinical sequencing
Zhe Yu, Zirui Zhang, Jun Liu, Xiaoying Wu, Xiaojun Fan, Jiaohui Pang, Hua Bao, Jiani Yin, Xue Wu, Yang Shao, Zhengcheng Liu, Fang Liu
Molecular Oncology.2024; 18(5): 1301. CrossRef
Germline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in Thailand
Chalermkiat Kansuttiviwat, Pongtawat Lertwilaiwittaya, Ekkapong Roothumnong, Panee Nakthong, Peerawat Dungort, Chutima Meesamarnpong, Warisara Tansa-Nga, Khontawan Pongsuktavorn, Supakit Wiboonthanasarn, Warunya Tititumjariya, Nannipa Phuphuripan, Chittap
npj Genomic Medicine.2024;[Epub] CrossRef
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Mugip Rahaman Abdul Wahab, Thirunavukkarasu Palaniyandi, Swarnakala Thamada, Sandhiya Viswanathan, Gomathy Baskar, Hemapreethi Surendran, P Baraneedharan, J Kannan, Maddaly Ravi, Suba Rajinikanth, Mohamed A. El-Tayeb, Shaban Syed
Clinica Chimica Acta.2024; 561: 119818. CrossRef
Towards targeting the breast cancer immune microenvironment
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Nature Reviews Cancer.2024; 24(8): 554. CrossRef
Genetic Testing Among Breast Cancer Patients in the Eastern Region of Saudi Arabia: Single-Center Experience
Ghadeer Al Ghareeb, Zainab Al Nass, Salma Abu-Grain, Alia Alnaji, Hani Almohanna, Hadi Al Shaikh Nasser, Saad Al Shahrani
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The Genomic and Biologic Landscapes of Breast Cancer and Racial Differences
Sapthala P Loku Galappaththi, Kelly R. Smith, Enas S. Alsatari, Rachel Hunter, Donna L. Dyess, Elba A. Turbat-Herrera, Santanu Dasgupta
International Journal of Molecular Sciences.2024; 25(23): 13165. CrossRef
Clinical usefulness of NGS multi-gene panel testing in hereditary cancer analysis
Federico Anaclerio, Lucrezia Pilenzi, Anastasia Dell’Elice, Rossella Ferrante, Simona Grossi, Luca Maria Ferlito, Camilla Marinelli, Simona Gildetti, Giuseppe Calabrese, Liborio Stuppia, Ivana Antonucci
Frontiers in Genetics.2023;[Epub] CrossRef
Triple-negative breast cancer: epidemiology, molecular mechanisms, and modern vaccine-based treatment strategies
Asad Mustafa Karim, Jeong Eun Kwon, Tanveer Ali, Jinsoo Jang, Irfan Ullah, Yeong-Geun Lee, Dae Won Park, Juha Park, Jin Woo Jeang, Se Chan Kang
Biochemical Pharmacology.2023; 212: 115545. CrossRef
Klinische Anwendungsbeispiele einer Next-Generation-Sequencing-basierten Multi-Genpanel-Analyse
Dietmar Enko, Erich Schaflinger, Daniel J. Müller
DMW - Deutsche Medizinische Wochenschrift.2023; 148(11): 695. CrossRef
A study of clinical and molecular characteristics in bilateral primary breast cancer
Bin Li, Weiqi Xu, Jianing Cao, Duancheng Guo, Zhonghua Tao, Juan Jin, Xichun Hu
Cancer Medicine.2023; 12(15): 15881. CrossRef
Klinische Anwendungsbeispiele einer Next-Generation-Sequencing-basierten Multi-Genpanel-Analyse
Dietmar Enko, Erich Schaflinger, Daniel J. Müller
TumorDiagnostik & Therapie.2023; 44(06): 401. CrossRef
Frequency of germline pathogenic variants in breast cancer predisposition genes among young Turkish breast cancer patients
Aysun Dauti Isiklar, Lamiya Aliyeva, Ahmet Yesilyurt, Aykut Soyder, Gul Basaran
Breast Cancer Research and Treatment.2023; 202(2): 297. CrossRef
Investigation of germline variants in Bahraini women with breast cancer using next-generation sequencing based-multigene panel
Ghada Al-Kafaji, Ghufran Jassim, Amani AlHajeri, Amna Mohamed Tayeb Alawadhi, Mariam Fida, Ibrahim Sahin, Faisal Alali, Elias Fadel, Amy McCart Reed
PLOS ONE.2023; 18(9): e0291015. CrossRef
Low prevalence of germline TP53 and PALB2 mutations in unselected cohort of breast cancer patients from Brunei Darussalam
Siti Nur Idayu Matusin, Zen Huat Lu, Mas Rina Wati Haji Abdul Hamid
F1000Research.2023; 12: 1537. CrossRef
Should all patients undergoing genetic testing for hereditary breast cancer syndromes be offered a multigene panel?
Erica L. Silver, Mariana Niell-Swiller
Current Opinion in Obstetrics & Gynecology.2022; 34(1): 36. CrossRef
The emerging roles of NGS in clinical oncology and personalized medicine
Bashdar Mahmud Hussen, Sara Tharwat Abdullah, Abbas Salihi, Dana Khdr Sabir, Karzan R. Sidiq, Mohammed Fatih Rasul, Hazha Jamal Hidayat, Soudeh Ghafouri-Fard, Mohammad Taheri, Elena Jamali
Pathology - Research and Practice.2022; 230: 153760. CrossRef
Increased incidence of pathogenic variants in ATM in the context of testing for breast and ovarian cancer predisposition
P. Macquere, S. Orazio, F. Bonnet, N. Jones, V. Bubien, J. Chiron, D. Lafon, E. Barouk-Simonet, J. Tinat, L. Venat-Bouvet, P. Gesta, M. Longy, N. Sevenet
Journal of Human Genetics.2022; 67(6): 339. CrossRef
Novel Insights From the Germline Landscape of Breast Cancer in Brazil
Daniel Barbalho, Renata Sandoval, Erika Santos, Janina Pisani, Carla Quirino, Bernardo Garicochea, Benedito Rossi, Maria Isabel Achatz
Frontiers in Oncology.2022;[Epub] CrossRef
Evaluation of a Four-Gene Panel for Hereditary Cancer Risk Assessment
Angela Secondino, Flavio Starnone, Iolanda Veneruso, Maria Di Tella, Serena Conato, Carmine De Angelis, Sabino De Placido, Valeria D’Argenio
Genes.2022; 13(4): 682. CrossRef
Multi-gene panel testing increases germline predisposing mutations’ detection in a cohort of breast/ovarian cancer patients from Southern Italy
Marcella Nunziato, Federica Di Maggio, Matilde Pensabene, Maria Valeria Esposito, Flavio Starnone, Carmine De Angelis, Alessandra Calabrese, Massimiliano D’Aiuto, Gerardo Botti, Sabino De Placido, Valeria D’Argenio, Francesco Salvatore
Frontiers in Medicine.2022;[Epub] CrossRef
Targeted Sequencing of Germline Breast Cancer Susceptibility Genes for Discovering Pathogenic/Likely Pathogenic Variants in the Jakarta Population
Sonar Soni Panigoro, Rafika Indah Paramita, Kristina Maria Siswiandari, Fadilah Fadilah
Diagnostics.2022; 12(9): 2241. CrossRef
Frequency of Pathogenic Germline Mutations in Early and Late Onset Familial Breast Cancer Patients Using Multi-Gene Panel Sequencing: An Egyptian Study
Auhood Nassar, Abdel-Rahman N. Zekri, Mahmoud M. Kamel, Mostafa H. Elberry, Mai M. Lotfy, Mohamed G. Seadawy, Zeinab K. Hassan, Hany K. Soliman, Ahmed M. Lymona, Amira Salah El-Din Youssef
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Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis
Renata Lazari Sandoval, Ana Carolina Rathsam Leite, Daniel Meirelles Barbalho, Daniele Xavier Assad, Romualdo Barroso, Natalia Polidorio, Carlos Henrique dos Anjos, Andréa Discaciati de Miranda, Ana Carolina Salles de Mendonça Ferreira, Gustavo dos Santos
PLOS ONE.2021; 16(2): e0247363. CrossRef
Molecular Diagnosis of Neurofibromatosis by Multigene Panel Testing
Zeng-Yun-Ou Zhang, Yuan-Yuan Wu, Xin-ying Cai, Wen-Liang Fang, Feng-Li Xiao
Frontiers in Genetics.2021;[Epub] CrossRef
Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach
Pratibha Bhai, Michael A. Levy, Kathleen Rooney, Deanna Alexis Carere, Jack Reilly, Jennifer Kerkhof, Michael Volodarsky, Alan Stuart, Mike Kadour, Karen Panabaker, Laila C. Schenkel, Hanxin Lin, Peter Ainsworth, Bekim Sadikovic
Frontiers in Genetics.2021;[Epub] CrossRef
Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge
M. Bono, D. Fanale, L. Incorvaia, D. Cancelliere, A. Fiorino, V. Calò, A. Dimino, C. Filorizzo, L.R. Corsini, C. Brando, G. Madonia, A. Cucinella, R. Scalia, N. Barraco, F. Guadagni, E. Pedone, G. Badalamenti, A. Russo, V. Bazan
ESMO Open.2021; 6(4): 100235. CrossRef
Summary of BARD1 Mutations and Precise Estimation of Breast and Ovarian Cancer Risks Associated with the Mutations
Malwina Suszynska, Piotr Kozlowski
Genes.2020; 11(7): 798. CrossRef
Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2
Daniele Fanale, Lorena Incorvaia, Clarissa Filorizzo, Marco Bono, Alessia Fiorino, Valentina Calò, Chiara Brando, Lidia Rita Corsini, Nadia Barraco, Giuseppe Badalamenti, Antonio Russo, Viviana Bazan
Cancers.2020; 12(9): 2415. CrossRef

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Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study: Sang Myung Woo, Min Kyeong Kim, Jungnam Joo, Kyong-Ah Yoon, Boram Park, Sang-Jae Park, Sung-Sik Han, Ju Hee Lee, Eun Kyung Hong, Yun-Hee Kim, Hae Moon, Sun-Young Kong, Tae Hyun Kim, Woo Jin Lee; Cancer Res Treat. 2017;49(4):1022-1032. Published online January 19, 2017; DOI: https://doi.org/10.4143/crt.2016.495

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
Materials and Methods
In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m²) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m²/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
Results
Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
Conclusion
Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

Citations

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Impact of treatment sequence and dose response on outcomes in locally advanced pancreatic cancer treated with hypofractionated proton beam therapy using simultaneous integrated boost technique
Tae Hyun Kim, Jung Won Chun, Sang Myung Woo, Joo-Hyun Chung, Min Hee Lee, Sung-Sik Han, Sang-Jae Park, Sung Uk Lee, Yang-Gun Suh, Sung Ho Moon, Sang Soo Kim, Woo Jin Lee
Radiotherapy and Oncology.2026; 214: 111295. CrossRef
Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma
Krishan R. Jethwa, Ed Kim, Jordan Berlin, Christopher J. Anker, Leila Tchelebi, Gerard Abood, Christopher L. Hallemeier, Salma Jabbour, Timothy Kennedy, Rachit Kumar, Percy Lee, Navesh Sharma, William Small, Vonetta Williams, Suzanne Russo
American Journal of Clinical Oncology.2024; 47(4): 185. CrossRef
Kinetics of plasma cell-free DNA as a prospective biomarker to predict the prognosis and radiotherapy effect of esophageal cancer
Y. Li, J. Wu, Y. Feng, D. Wang, H. Tao, J. Wen, F. Jiang, P. Qian, Y. Liu
Cancer/Radiothérapie.2024; 28(3): 242. CrossRef
Circulating tumor DNA in unresectable pancreatic cancer is a strong predictor of first-line treatment efficacy: The KRASCIPANC prospective study
Camille Evrard, Pierre Ingrand, Tristan Rochelle, Marine Martel, Gaëlle Tachon, Nicolas Flores, Violaine Randrian, Aurélie Ferru, Paul-Arthur Haineaux, Jean-Michel Goujon, Lucie Karayan-Tapon, David Tougeron
Digestive and Liver Disease.2023; 55(11): 1562. CrossRef
Circulating tumor DNA: a help to guide therapeutic strategy in patients with borderline and locally advanced pancreatic adenocarcinoma?
Olivier Caliez, Daniel Pietrasz, Feryel Ksontini, Solène Doat, Jean-Marc Simon, Jean-Christophe Vaillant, Valerie Taly, Pierre Laurent-Puig, Jean-Baptiste Bachet
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Marisol Huerta, Susana Roselló, Luis Sabater, Ana Ferrer, Noelia Tarazona, Desamparados Roda, Valentina Gambardella, Clara Alfaro-Cervelló, Marina Garcés-Albir, Andrés Cervantes, Maider Ibarrola-Villava
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Clinical Utility of Liquid Biopsy-Based Actionable Mutations Detected via ddPCR
Irina Palacín-Aliana, Noemí García-Romero, Adrià Asensi-Puig, Josefa Carrión-Navarro, Víctor González-Rumayor, Ángel Ayuso-Sacido
Biomedicines.2021; 9(8): 906. CrossRef
A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers
Sheng-Nan Jia, Fu-Xing Wen, Ting-Ting Gong, Xin Li, Hui-Jie Wang, Ya-Min Sun, Ze-Cheng Yang
International Journal of Radiation Biology.2020; 96(3): 383. CrossRef
Efficacy and feasibility of proton beam radiotherapy using the simultaneous integrated boost technique for locally advanced pancreatic cancer
Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo, Eun Sang Oh, Sang Hee Youn, Hye Young Jang, Sung-Sik Han, Sang-Jae Park, Yang-Gun Suh, Sung Ho Moon, Sang Soo Kim, Dae Yong Kim
Scientific Reports.2020;[Epub] CrossRef
Comprehensive Cancer Panel Sequencing Defines Genetic Diversity and Changes in the Mutational Characteristics of Pancreatic Cancer Patients Receiving Neoadjuvant Treatment
Kyong-Ah Yoon, Sang Myung Woo, Yun-Hee Kim, Sun-Young Kong, Min Kyoung Lee, Sung-Sik Han, Tae Hyun Kim, Woo Jin Lee, Sang-Jae Park
Gut and Liver.2019; 13(6): 683. CrossRef
Plasma Cell-Free DNA as a Predictive Marker after Radiotherapy for Hepatocellular Carcinoma
Sangjoon Park, Eun Jung Lee, Chai Hong Rim, Jinsil Seong
Yonsei Medical Journal.2018; 59(4): 470. CrossRef
Effectiveness and Safety of Simultaneous Integrated Boost-Proton Beam Therapy for Localized Pancreatic Cancer
Tae Hyun Kim, Woo Jin Lee, Sang Myung Woo, Hyunjung Kim, Eun Sang Oh, Ju Hee Lee, Sung-Sik Han, Sang-Jae Park, Yang-Gun Suh, Sung Ho Moon, Sang Soo Kim, Dae Yong Kim
Technology in Cancer Research & Treatment.2018;[Epub] CrossRef

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Clinically Significant Unclassified Variants in BRCA1 and BRCA2 Genes among Korean Breast Cancer Patients: Kyong-Ah Yoon, Boyoung Park, Byung Il Lee, Moon Jung Yang, Sun-Young Kong, Eun Sook Lee; Cancer Res Treat. 2017;49(3):627-634. Published online September 13, 2016; DOI: https://doi.org/10.4143/crt.2016.292

Abstract PDF PubReader ePub

Purpose
Unclassified variants (UVs) of BRCA1 and BRCA2 genes are not defined as pathogenic for breast cancer, and their clinical significance currently remains undefined. Therefore, this study was conducted to identify potentially pathogenic UVs by comparing their prevalence between breast cancer patients and controls.
Materials and Methods
A total of 328 breast cancer patients underwent BRCA1/2 genetic screening at the National Cancer Center of Korea. Genetic variants of BRCA genes that were categorized as unclassified according to the Breast CancerInformation Core databasewere selected based on allelic frequency, after which candidate variants were genotyped in 421 healthy controls. We also examined family members of the study participants. Finally, the effects of amino acid substitutions on protein structure and function were predicted in silico.
Results
Genetic tests revealed 33 UVs in BRCA1 and 47 in BRCA2. Among 15 candidates genotyped in healthy controls, c.5339T>C in BRCA1 and c.6029T>G, c.7522G>A in BRCA2 were not detected. Moreover, the c.5339T>C variant in the BRCA1 gene was detected in four patients with a family history of breast cancer. This nonsynonymous variant (Leu1780Pro) in the BRCA1 C-terminal domain was predicted to have an effect on BRCA1 protein structure/function.
Conclusion
This study showed that comparison of genotype frequency between cases and controls could help identify UVs of BRCA genes that are potentially pathogenic. Moreover, ourfindings suggest that c.5339T>C in BRCA1 might be a pathogenic variant for patients and their families.

Citations

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Global prevalence and ethnic variation of pathogenic BRCA1/2 variants in breast cancer: a systematic review and meta-analysis
Najeeb Ullah Khan, Huijun Lei, Jinzhen Fu, Ruijiao Lei, Xukai Chen, Sana S. Alqarni, Tianhui Chen
Journal of Translational Medicine.2026;[Epub] CrossRef
Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
Cancers.2022; 14(10): 2405. CrossRef
Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
Scientific Reports.2021;[Epub] CrossRef
Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant
Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
Cancer Research and Treatment.2020; 52(3): 680. CrossRef
Identification of Recurrent Variants in BRCA1 and BRCA2 across Multiple Cancers in the Chinese Population
Yue Jiang, Ting Tian, Chengxiao Yu, Wen Zhou, Junzhe Yang, Yifeng Wang, Yang Wen, Jiaping Chen, Juncheng Dai, Guangfu Jin, Hongxia Ma, Hongbing Shen, Zhibin Hu, Yu-Chang Tyan
BioMed Research International.2020;[Epub] CrossRef
Reinterpretation of BRCA1 and BRCA2 variants of uncertain significance in patients with hereditary breast/ovarian cancer using the ACMG/AMP 2015 guidelines
Min-Kyung So, Tae-Dong Jeong, Woosung Lim, Byung-In Moon, Nam Sun Paik, Seung Cheol Kim, Jungwon Huh
Breast Cancer.2019; 26(4): 510. CrossRef
BRCA gene mutations: A population based review
Ratika Samtani, Deepti Saksena
Gene Reports.2019; 15: 100380. CrossRef
Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer
Min Chul Choi, Ja-Hyun Jang, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Je Ho Lee
International Journal of Gynecological Cancer.2018; 28(2): 308. CrossRef
Differences in attitudes toward genetic testing among the public, patients, and health-care professionals in Korea
Heesang Eum, Mangyeong Lee, Junghee Yoon, Juhee Cho, Eun Sook Lee, Kui Son Choi, Sangwon Lee, So-Youn Jung, Myong Cheol Lim, Sun-Young Kong, Yoon Jung Chang
European Journal of Human Genetics.2018; 26(10): 1432. CrossRef
Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort
Jee-Soo Lee, Sohee Oh, Sue Kyung Park, Min-Hyuk Lee, Jong Won Lee, Sung-Won Kim, Byung Ho Son, Dong-Young Noh, Jeong Eon Lee, Hai-Lin Park, Man Jin Kim, Sung Im Cho, Young Kyung Lee, Sung Sup Park, Moon-Woo Seong
Journal of Medical Genetics.2018; 55(12): 794. CrossRef
Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from ‘unknown significance’ to ‘Likely pathogenic’ based on clinical evidence in Korea
Jai Min Ryu, Goeun Kang, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Se Kyung Lee, Soo Youn Bae, Sungmin Park, Hyun-June Paik, Jong-Won Kim, Sung-Shin Park, Jeong Eon Lee, Sung-Won Kim
The Breast.2017; 33: 109. CrossRef

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515 Download
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Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer: Jungnam Joo, Kyong-Ah Yoon, Tomonori Hayashi, Sun-Young Kong, Hye-Jin Shin, Boram Park, Young Min Kim, Sang-Hyun Hwang, Jeongseon Kim, Aesun Shin, Joo-Young Kim; Cancer Res Treat. 2016;48(2):708-714. Published online June 22, 2015; DOI: https://doi.org/10.4143/crt.2015.098

Abstract PDF Supplementary Material PubReader ePub

Purpose
Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer.
Materials and Methods
Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed.
Results
The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type.
Conclusion
The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.

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