BACKGROUND: Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damage by means of repair enzymes. Genotypic variants of DNA damage repair genes, participating in base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. METHODS: In a hospital-based case-control study of female breast cancer, DNA samples were obtained from 401 cases and 533 enrolled healthy controls, all of whom were Chinese women in Taiwan. Genotyping of polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Ser662Pro, and ERCC5 His1104Asp was performed and used to evaluate breast cancer susceptibility. RESULTS: Of the nonsynonymous polymorphisms, the ERCC5 1104Asp variant was significantly associated with breast cancer (odds ratio = 1.42; 95% confidence interval = 1.08-1.97), and this association was more pronounced in women with lengthy estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (P(trend) = .038). The synergistic effect of multiple genes on the increase of risk was significant in women with a longer period of estrogen exposure (>26 years), greater age at first full-term pregnancy (>26 years), a longer menarche-to-first full-term pregnancy interval (>11 years), and higher body mass index (>22) (all P<.05). CONCLUSIONS: This study demonstrates that genotype polymorphisms related to DNA damage repair confer greater susceptibility to endogenous estrogen in the development of breast cancer in women.
BACKGROUND: Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damage by means of repair enzymes. Genotypic variants of DNA damage repair genes, participating in base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. METHODS: In a hospital-based case-control study of female breast cancer, DNA samples were obtained from 401 cases and 533 enrolled healthy controls, all of whom were Chinese women in Taiwan. Genotyping of polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2Lys751Gln, ERCC4Ser662Pro, and ERCC5His1104Asp was performed and used to evaluate breast cancer susceptibility. RESULTS: Of the nonsynonymous polymorphisms, the ERCC5 1104Asp variant was significantly associated with breast cancer (odds ratio = 1.42; 95% confidence interval = 1.08-1.97), and this association was more pronounced in women with lengthy estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (P(trend) = .038). The synergistic effect of multiple genes on the increase of risk was significant in women with a longer period of estrogen exposure (>26 years), greater age at first full-term pregnancy (>26 years), a longer menarche-to-first full-term pregnancy interval (>11 years), and higher body mass index (>22) (all P<.05). CONCLUSIONS: This study demonstrates that genotype polymorphisms related to DNA damage repair confer greater susceptibility to endogenous estrogen in the development of breast cancer in women.
Authors: Alexandra S Shadrina; Natalia A Ermolenko; Uljana A Boyarskikh; Tatiana V Sinkina; Alexandr F Lazarev; Valentina D Petrova; Maxim L Filipenko Journal: Clin Exp Med Date: 2014-12-24 Impact factor: 3.984
Authors: Magdalena M Michalska; Dariusz Samulak; Hanna Romanowicz; Jan Bieńkiewicz; Maciej Sobkowski; Krzysztof Ciesielski; Beata Smolarz Journal: Tumour Biol Date: 2015-06-30
Authors: Luís S Santos; Susana N Silva; Octávia M Gil; Teresa C Ferreira; Edward Limbert; José Rueff Journal: Oncol Lett Date: 2018-02-21 Impact factor: 2.967
Authors: Ana Osorio; Roger L Milne; Karoline Kuchenbaecker; Tereza Vaclová; Guillermo Pita; Rosario Alonso; Paolo Peterlongo; Ignacio Blanco; Miguel de la Hoya; Mercedes Duran; Orland Díez; Teresa Ramón Y Cajal; Irene Konstantopoulou; Cristina Martínez-Bouzas; Raquel Andrés Conejero; Penny Soucy; Lesley McGuffog; Daniel Barrowdale; Andrew Lee; Brita Arver; Johanna Rantala; Niklas Loman; Hans Ehrencrona; Olufunmilayo I Olopade; Mary S Beattie; Susan M Domchek; Katherine Nathanson; Timothy R Rebbeck; Banu K Arun; Beth Y Karlan; Christine Walsh; Jenny Lester; Esther M John; Alice S Whittemore; Mary B Daly; Melissa Southey; John Hopper; Mary B Terry; Saundra S Buys; Ramunas Janavicius; Cecilia M Dorfling; Elizabeth J van Rensburg; Linda Steele; Susan L Neuhausen; Yuan Chun Ding; Thomas V O Hansen; Lars Jønson; Bent Ejlertsen; Anne-Marie Gerdes; Mar Infante; Belén Herráez; Leticia Thais Moreno; Jeffrey N Weitzel; Josef Herzog; Kisa Weeman; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Giulietta Scuvera; Bernardo Bonanni; Frederique Mariette; Sara Volorio; Alessandra Viel; Liliana Varesco; Laura Papi; Laura Ottini; Maria Grazia Tibiletti; Paolo Radice; Drakoulis Yannoukakos; Judy Garber; Steve Ellis; Debra Frost; Radka Platte; Elena Fineberg; Gareth Evans; Fiona Lalloo; Louise Izatt; Ros Eeles; Julian Adlard; Rosemarie Davidson; Trevor Cole; Diana Eccles; Jackie Cook; Shirley Hodgson; Carole Brewer; Marc Tischkowitz; Fiona Douglas; Mary Porteous; Lucy Side; Lisa Walker; Patrick Morrison; Alan Donaldson; John Kennedy; Claire Foo; Andrew K Godwin; Rita Katharina Schmutzler; Barbara Wappenschmidt; Kerstin Rhiem; Christoph Engel; Alfons Meindl; Nina Ditsch; Norbert Arnold; Hans Jörg Plendl; Dieter Niederacher; Christian Sutter; Shan Wang-Gohrke; Doris Steinemann; Sabine Preisler-Adams; Karin Kast; Raymonda Varon-Mateeva; Andrea Gehrig; Dominique Stoppa-Lyonnet; Olga M Sinilnikova; Sylvie Mazoyer; Francesca Damiola; Bruce Poppe; Kathleen Claes; Marion Piedmonte; Kathy Tucker; Floor Backes; Gustavo Rodríguez; Wendy Brewster; Katie Wakeley; Thomas Rutherford; Trinidad Caldés; Heli Nevanlinna; Kristiina Aittomäki; Matti A Rookus; Theo A M van Os; Lizet van der Kolk; J L de Lange; Hanne E J Meijers-Heijboer; A H van der Hout; Christi J van Asperen; Encarna B Gómez Garcia; Nicoline Hoogerbrugge; J Margriet Collée; Carolien H M van Deurzen; Rob B van der Luijt; Peter Devilee; Edith Olah; Conxi Lázaro; Alex Teulé; Mireia Menéndez; Anna Jakubowska; Cezary Cybulski; Jacek Gronwald; Jan Lubinski; Katarzyna Durda; Katarzyna Jaworska-Bieniek; Oskar Th Johannsson; Christine Maugard; Marco Montagna; Silvia Tognazzo; Manuel R Teixeira; Sue Healey; Curtis Olswold; Lucia Guidugli; Noralane Lindor; Susan Slager; Csilla I Szabo; Joseph Vijai; Mark Robson; Noah Kauff; Liying Zhang; Rohini Rau-Murthy; Anneliese Fink-Retter; Christian F Singer; Christine Rappaport; Daphne Geschwantler Kaulich; Georg Pfeiler; Muy-Kheng Tea; Andreas Berger; Catherine M Phelan; Mark H Greene; Phuong L Mai; Flavio Lejbkowicz; Irene Andrulis; Anna Marie Mulligan; Gord Glendon; Amanda Ewart Toland; Anders Bojesen; Inge Sokilde Pedersen; Lone Sunde; Mads Thomassen; Torben A Kruse; Uffe Birk Jensen; Eitan Friedman; Yael Laitman; Shani Paluch Shimon; Jacques Simard; Douglas F Easton; Kenneth Offit; Fergus J Couch; Georgia Chenevix-Trench; Antonis C Antoniou; Javier Benitez Journal: PLoS Genet Date: 2014-04-03 Impact factor: 5.917