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

This genome-wide association study identified a 1.7– 1.8-fold increase in likelihood of post-chemotherapy menses in patients who carried the minor alleles of SNPs in PPCDC and near RPS20P11.

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Volume 112, Issue 4, Pages 731–739.e1

Authors:

Kathryn J. Ruddy, M.D., M.P.H., Daniel J. Schaid, Ph.D., Ann H. Partridge, M.D., Nicholas B. Larson, Ph.D., Anthony Batzler, B.S., Lothar Häberle, Ph.D., Ralf Dittrich, Ph.D., Peter Widschwendter, M.D., Visnja Fink, M.D., Emanuel Bauer, M.D., Judith Schwitulla, Ph.D., Matthias Rübner, Ph.D., Arif B. Ekici, Ph.D., Viktoria Aivazova-Fuchs, M.D., Elizabeth A. Stewart, M.D., Matthias W. Beckmann, M.D., Elizabeth Ginsburg, M.D., Liewei Wang, M.D., Richard M. Weinshilboum, M.D., Fergus J. Couch, Ph.D., Wolfgang Janni, M.D., Brigitte Rack, M.D., Celine Vachon, Ph.D., Peter A. Fasching, M.D.

Abstract:

Objective

To study how genetics may play a role in determining risk of chemotherapy-related amenorrhea (CRA) in young women with breast cancer.

Design

Genome-wide association study.

Setting

Not applicable.

Patient(s)

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.

Intervention(s)

None.

Main Outcome Measure(s)

The association of single-nucleotide polymorphisms with post-chemotherapy menstruation adjusted for trial and arm, age, tamoxifen use, and nodal status.

Result(s)

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.

Conclusion(s)

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.


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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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