Gender Disparities in the Tumor Genetics and Clinical Outcome
of Multiple Myeloma
Kevin D. Boyd1, Fiona M. Ross2, Laura Chiecchio2, GianPaolo Dagrada2, Zoe J. Konn2, William J. Tapper2,
Brian A. Walker1, Christopher P. Wardell1, Walter M. Gregory3, Alex J. Szubert3,
Faith E. Davies1, and Gareth J. Morgan1
Background: Several cancer types havedifferences in incidence andclinical outcome dependent ongender,
but these are not well described in myeloma. The aim of this study was to characterize gender disparities in
Methods: We investigated the association of gender with the prevalence of tumor genetic lesions and the
clinical outcome of 1,960 patients enrolled in the phase IIIclinical trial MRC Myeloma IX. Genetic lesions were
characterized by FISH.
Results: Disparities were found in the prevalence of primary genetic lesions with immunoglobulin heavy
chain gene (IGH) translocations being more common in women (50% of female patients vs. 38% of male
were also differences in secondary genetic events with del(13q) (52% female vs. 41% male, P < 0.001) and þ1q
was associated with inferior overall survival (median: 44.8 months female vs. 49.9 months male, P ¼ 0.020).
Conclusions: We found gender-dependent differences in the prevalence of the primary genetic events of
myeloma, with IGH translocations being more common in women and hyperdiploidy more common in men.
This genetic background may impact subsequent genetic events such as þ1q and del(13q), which were both
more frequent in women. The higher prevalence of lesions associated with poor prognosis in the female
myeloma population, such as t(4;14), t(14;16) and þ1q, may adversely affect clinical outcome.
Impact: These differences suggest that gender influences the primary genetic events of myeloma. Cancer
Epidemiol Biomarkers Prev; 20(8); 1703–7. ?2011 AACR.
Several cancer types have differences in incidence and
clinical outcome dependent on gender (1). Lung cancer,
for example, is more common in men, and women with
lung cancer have better survival than men (2). Moreover,
a sex-specific tumor genomic profile has been described
in lung cancer, strongly suggesting that there is a gender-
specific phenotype (2, 3). These data suggest that gender
can influence the etiology and natural history of some
In myeloma, the primary genetic lesions that give rise
to a clonal plasma cell population are hyperdiploidy
and immunoglobulin heavy chain gene (IGH) transloca-
tions (4). Hyperdiploidy in myeloma is characterized
by gain of multiple odd numbered chromosomes, and
the events giving rise to this abnormality are not well
understood. IGH translocations arise following aberrant
class switch recombination events during B-cell differ-
entiation and feature reciprocal translocation of the IGH
allele at 14q32, usually with one of 5 partner oncogenes
(FGFR3, CCND1, CCND3, MAF, or MAFB; refs. 5, 6).
These two etiologic pathways have been used to classify
myeloma patients into a hyperdiploid group and non-
hyperdiploid group characterized by a high rate of IGH
translocations (5, 7). These early genetic events give rise
to a clonal plasma cell population, with further events
such as structural chromosomal abnormalities, mutation,
and epigenetic changes required for progression to
It is unknown why these pathogenic events occur in
certain individuals but evidence of genetic susceptibility
Cancer Research, London;2Wessex Regional Genetics Laboratory, Uni-
versity of Southampton, Salisbury; and
University of Leeds, Leeds, United Kingdom
1Section of Haemato-Oncology, The Institute of
3Clinical Trials Research Unit,
Note: Supplementary data for this article are available at Cancer Epide-
miology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).
Corresponding Author: Gareth J. Morgan, The Institute of Cancer
Research, Section of Haemato-Oncology, 15 Cotswold Road, Sutton,
Surrey SM2 5NG, United Kingdom. Phone: 442087224130; Fax:
442087224432; E-mail: email@example.com
?2011 American Association for Cancer Research.