Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer

To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Genome-wide association study. Not applicable. Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menst...

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Veröffentlicht in:Fertility and sterility 2019-10, Vol.112 (4), p.731-739.e1
Hauptverfasser: Ruddy, Kathryn J., Schaid, Daniel J., Partridge, Ann H., Larson, Nicholas B., Batzler, Anthony, Häberle, Lothar, Dittrich, Ralf, Widschwendter, Peter, Fink, Visnja, Bauer, Emanuel, Schwitulla, Judith, Rübner, Matthias, Ekici, Arif B., Aivazova-Fuchs, Viktoria, Stewart, Elizabeth A., Beckmann, Matthias W., Ginsburg, Elizabeth, Wang, Liewei, Weinshilboum, Richard M., Couch, Fergus J., Janni, Wolfgang, Rack, Brigitte, Vachon, Celine, Fasching, Peter A.
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Sprache:eng
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Zusammenfassung:To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer. Genome-wide association study. Not applicable. Premenopausal women ≤45 years of age enrolled in one of these three trials were included if they had at least one menstrual case report form after chemotherapy ended and if they were of European ancestry. Forms during and up to 3 months after receipt of GnRH agonist were excluded. None. The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status. The median age of the 1,168 women was 41 years (range 19–45). Among these, 457 (39%) never resumed menses after chemotherapy. Older age, tamoxifen use, and node-negative disease were associated with increased risk of CRA. Adjusting for these, rs147451859, in an intron of PPCDC (phosphopantothenoylcysteine decarboxylase), and rs17587029, located 5′ upstream of RPS20P11 (ribosomal protein S20 pseudogene 11), were associated with post-chemotherapy menstruation. Genetic variation may contribute to risk of CRA. Better prediction of who will experience CRA may inform reproductive and treatment decision making in young women with cancer. Predictores genéticos de amenorrea relacionados con quimioterapia en mujeres con cáncer de mama estudiar cómo la genética puede desempeñar un papel en la determinación del riesgo de amenorrea relacionada con la quimioterapia (CRA) en mujeres jóvenes con cáncer de mama. Estudio de asociación del genoma completo. No aplica. mujeres premenopáusicas ≤ de 45 años fueron inscritas en uno de estos tres ensayos si tenían al menos un informe de caso de menstruación después de que finalizó la quimioterapia y si eran de ascendencia europea. Formularios durante y hasta 3 meses después de recibir agonista de GnRH fueron excluidas. Ninguna. La asociación de polimorfismos de un solo nucleótido con menstruación post-quimioterapia ajustada por ensayo y brazo, edad, uso de tamoxifeno, y estado ganglionar. La media de edad de las 1,168 mujeres fue 41 años (rango 19-45). Entre estas, 457 (39%) nunca reanudaron menstruaciones después de la quimioterapia. La edad avanzada, uso de tamoxifeno, y enfermedad con ganglio negativo fueron asociados con mayor riesgo de CRA. Ajustando por esto, rs 147451859, en un intrón de PPCDC (fosfopantotenoilcisteína descarboxilasa), y rs 17587029, localizado corriente arriba 5' de RPS20P11 (proteína ribosomal S
ISSN:0015-0282
1556-5653
DOI:10.1016/j.fertnstert.2019.05.018