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BMC Cancer. 2016 May 27;16:337. doi: 10.1186/s12885-016-2373-3.

SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.

Author information

1
Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany. toralf.reimer@med.uni-rostock.de.
2
Department of Obstetrics and Gynecology, University of Rostock, Klinikum Suedstadt, Suedring 81, Rostock, 18059, Germany.
3
Institute of Immunology, University of Rostock, P.O.B. 100888, Rostock, 18055, Germany.

Abstract

BACKGROUND:

Because inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.

METHODS:

Our approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m(2) for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.

RESULTS:

Twenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05-0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.

CONCLUSIONS:

Patient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.

KEYWORDS:

Breast cancer; Chemotherapy-induced amenorrhea; OpenArray genotyping; SLCO1B1; Single nucleotide polymorphism

PMID:
27234217
PMCID:
PMC4884353
DOI:
10.1186/s12885-016-2373-3
[Indexed for MEDLINE]
Free PMC Article

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