Philippa Lloyd1, Mark Westcott2,3,4, Swathi Kaliki5, Xunda Ji6, Yihua Zou6, Riffat Rashid7, Sadia Sultana7, Sadik Taju Sherief8, Nathalie Cassoux9, Rosdali Yesenia Diaz Coronado10, Juan Luis Garcia Leon11, Arturo Manuel Zapata López10, Vladimir G Polyakov12, Tatiana L Ushakova12, Soma Rani Roy13, Alia Ahmad14, Lamis Al Harby2,4, Jesse L Berry15, Jonathan Kim15, Ashley Polski15, Nicholas J Astbury16, Covadonga Bascaran16, Sharon Blum17, Richard Bowman16,18, Matthew J Burton16, Allen Foster16, Nir Gomel19, Naama Keren-Froim20, Shiran Madgar17, Andrew W Stacey21, Ashik Mohamed22, Marcia Zondervan16, Mandeep S Sagoo2,3,4,23, Ido Didi Fabian16,17, M Ashwin Reddy24,25,26. 1. Barts and The London School of Medicine and Dentistry, London, E1 2AD, UK. 2. The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK. 3. UCL Institute of Ophthalmology, London, EC1V 9EL, UK. 4. Moorfields Eye Hospital NHS Foundation Trust, London, EC1V 2PD, UK. 5. The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad, 500034, India. 6. Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. 7. Ocular Oncology, Ispahani Islamia Eye Institute and Hospital, Dhaka, 1215, Bangladesh. 8. Addis Ababa University, School of Medicine, Department of Ophthalmology, Addis Ababa, 3614, Ethiopia. 9. Institut Curie, Université de Paris Medicine Paris V Descartes, Paris, 75248, France. 10. Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru. 11. Anglo American Clinic, Lima, 15073, Peru. 12. Head and Neck Tumors Department, SRI of Pediatric Oncology and Hematology of N.N. Blokhin National Medical Research Center of Oncology of Russian Federation, and Medical Academy of Postgraduate Education, Moscow, 115478, Russia. 13. Chittagong Eye Infirmary & Training Complex, Chittagong, 4202, Bangladesh. 14. The Children's Hospital & the Institute of Child Health, Lahore, 54000, Pakistan. 15. Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90027, USA. 16. International Centre for Eye Health, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK. 17. Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Tel-Aviv, 52621, Israel. 18. Ophthalmology Department, Great Ormond Street Children's Hospital, London, WC1N 3JH, UK. 19. Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 39040, Israel. 20. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 39040, Israel. 21. Department of Ophthalmology, University of Washington, Seattle, WA, 98195, USA. 22. Ophthalmic Biophysics (AMd), L V Prasad Eye Institute, Hyderabad, 500034, India. 23. NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and UCL Institute of Ophthalmology and London Retinoblastoma Service, Royal London Hospital, London, EC1V 2PD, UK. 24. The Royal London Hospital, Barts Health NHS Trust, London, E1 1FR, UK. ashwin.reddy4@nhs.net. 25. Moorfields Eye Hospital NHS Foundation Trust, London, EC1V 2PD, UK. ashwin.reddy4@nhs.net. 26. Queen Mary University of London, London, E1 4NS, UK. ashwin.reddy4@nhs.net.
Abstract
BACKGROUND/ OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/ METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.
BACKGROUND/ OBJECTIVES: Retinoblastoma is a common childhood intraocular malignancy, the bilateral form of which most commonly results from a de novo germline pathogenic variant in the RB1 gene. Both advanced maternal age and decreasing birth order are known to increase the risk of de novo germline pathogenic variants, while the influence of national wealth is understudied. This cohort study aimed to retrospectively observe whether these factors influence the ratio of bilateral retinoblastoma cases compared to unilateral retinoblastoma, thereby inferring an influence on the development of de novo germline pathogenic variants in RB1. SUBJECTS/ METHODS: Data from 688 patients from 11 centres in 10 countries were analysed using a series of statistical methods. RESULTS: No associations were found between advanced maternal age, birth order or GDP per capita and the ratio of bilateral to unilateral retinoblastoma cases (p values = 0.534, 0.201, 0.067, respectively), indicating that these factors do not contribute to the development of a de novo pathogenic variant. CONCLUSIONS: Despite a lack of a definitive control group and genetic testing, this study demonstrates that advanced maternal age, birth order or GDP per capita do not influence the risk of developing a bilateral retinoblastoma.
Authors: Andrew W Stacey; Richard Bowman; Allen Foster; Tero T Kivelä; Francis L Munier; Nathalie Cassoux; Ido Didi Fabian; Lamis Al Harby; Silvia Alarcón Portabella; Donjeta B Alia; Charlotta All-Eriksson; Romanzo Antonino; Nicholas J Astbury; Julia Balaguer; Walentyna Balwierz; Honorio Barranco; Covadonga Bascaran; Maja Beck Popovic; Eva M Biewald; Nadia Bobrova; Norbert Bornfeld; Bénédicte G Brichard; Sharon Blum; Michael Capra; Guilherme Castela; Jaume Català-Mora; Guillermo L Chantada; Violeta S Chernodrinska; Krzysztof Cieslik; Codruta Comsa; Maria G Correa Llano; Monika Csóka; Patrick De Potter; Laurence Desjardins; Monica D Dragomir; Ana Fernández-Teijeiro; David García Aldana; Pernille A Gregersen; Nir Gomel; Theodora Hadjistilianou; Stanislava Hederova; Marlies Hummlen; Kristina Husakova; Russo Ida; Vesna R Ilic; Helen Jenkinson; Noa Kapelushnik; Tamar Kardava; Naama Keren-Froim; Tomas Kepak; Zaza Khotenashvili; Artur Klett; Dalia Krivaitiene; Slobodanka Latinović; Livia Lumbroso; Lesia Lysytsia; Erika Maka; Nieves Martín Begue; Edoardo Midena; Annette C Moll; Gabriela Murgoi; Larisa Naumenko; Vladimir Neroev; Marina Nikitovic; Andrzej Olechowski; Ruzanna Papyan; Raffaele Parrozzani; Manoj V Parulekar; Katarzyna Pawinska-Wasikowska; Sanja Perić; Pavel Pochop; Vladimir G Polyakov; M Ashwin Reddy; Petra Ritter-Sovinz; Svetlana Saakyan; Mandeep S Sagoo; Sonsoles San Román Pacheco; Stefan Seregard; Sónia Silva; Tetyana Sorochynska; Christina Stathopoulos; Branka Stirn Kranjc; Karel Svojgr; Gevorg Tamamyan; Alketa Tandili; Bekim Tateshi; Manca Tekavcic Pompe; Steen F Urbak; Tatiana L Ushakova; Sandra Valeina; Milo van Hoefen Wijsard; Nevyana V Veleva-Krasteva; Maris Viksnins; Werner Wackernagel; Charlotte Wolley Dod; Vera A Yarovaya; Andrey A Yarovoy; Katsiaryna Zhilyaeva; Marcia Zondervan Journal: Ophthalmology Date: 2021-01-25 Impact factor: 12.079
Authors: A C Moll; D J Kuik; L M Bouter; W Den Otter; P D Bezemer; J W Koten; S M Imhof; B P Kuyt; K E Tan Journal: Br J Ophthalmol Date: 1997-07 Impact factor: 4.638
Authors: A MacCarthy; J M Birch; G J Draper; J L Hungerford; J E Kingston; M E Kroll; Z Onadim; C A Stiller; T J Vincent; M F G Murphy Journal: Br J Ophthalmol Date: 2008-10-06 Impact factor: 4.638
Authors: Tamara Marees; Annette C Moll; Saskia M Imhof; Michiel R de Boer; Peter J Ringens; Flora E van Leeuwen Journal: J Natl Cancer Inst Date: 2008-12-09 Impact factor: 13.506