Gender Disparities in the Tumor Genetics and Clinical Outcome of Multiple Myeloma

Overview

Journal Cancer Epidemiol Biomarkers Prev

Specialties Biochemistry
Oncology
Public Health

Date 2011 Jun 18

PMID 21680536

Citations 19

Authors

Kevin D Boyd

Fiona M Ross

Laura Chiecchio

Gianpaolo Dagrada

Zoe J Konn

William J Tapper

Brian A Walker

Christopher P Wardell

Walter M Gregory

Alex J Szubert

Faith E Davies

Gareth J Morgan

Affiliations

Soon will be listed here.

Abstract

Background: Several cancer types have differences in incidence and clinical outcome dependent on gender, but these are not well described in myeloma. The aim of this study was to characterize gender disparities in myeloma.

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 III clinical 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 patients, P < 0.001) and hyperdiploidy being more common in men (50% female vs. 62% male, P < 0.001). There were also differences in secondary genetic events with del(13q) (52% female vs. 41% male, P < 0.001) and +1q (43% female vs. 36% male, P = 0.042) being found more frequently in female myeloma patients. Female gender was associated with inferior overall survival (median: 44.8 months female vs. 49.9 months male, P = 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 +1q 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 +1q, may adversely affect clinical outcome.

Impact: These differences suggest that gender influences the primary genetic events of myeloma.

Citing Articles

Gender-Specific Prognostic Impact of Treosulfan Levels in High-Dose Chemotherapy for Multiple Myeloma.

Heini A, Kammermann K, Bacher U, Jeker B, Hayoz M, Aebi Y Cancers (Basel). 2024; 16(19).

PMID: 39409984 PMC: 11475554. DOI: 10.3390/cancers16193364.

Cytogenetic Alterations and Correlation with Age and Gender in Patients of Multiple Myeloma: A Study from a Tertiary Care Center in Eastern India.

Jha K, Saha S, Bhattacharyya M South Asian J Cancer. 2024; 13(2):126-131.

PMID: 38919660 PMC: 11196154. DOI: 10.1055/s-0043-1761441.

Multiple myeloma incidence and mortality trends in the United States, 1999-2020.

Zhu D, Park A, Lai A, Zhang L, Attar H, Rebbeck T Sci Rep. 2024; 14(1):14564.

PMID: 38914692 PMC: 11196710. DOI: 10.1038/s41598-024-65590-4.

Health Disparities Experienced by Hispanic Americans with Multiple Myeloma: A Systematic Review.

Anampa-Guzman A, Taveras Alam S, Abuali I, Al Hadidi S Clin Hematol Int. 2022; 5(1):29-37.

PMID: 36586086 PMC: 10063691. DOI: 10.1007/s44228-022-00026-2.

Risk Assessment for Newly Diagnosed Fit Young Patients with Multiple Myeloma in the Era of Novel Treatment Modalities: Should There Be Additional Factors Taken into Consideration??.

Kaloyannidis P, Abdulla F, Mutahar E, Al Hashim H, Al Harbi S, Estanislao A J Blood Med. 2022; 13:619-630.

PMID: 36317167 PMC: 9617519. DOI: 10.2147/JBM.S380133.

References

Fonseca R, Debes-Marun C, Picken E, Dewald G, Bryant S, Winkler J . The recurrent IgH translocations are highly associated with nonhyperdiploid variant multiple myeloma. Blood. 2003; 102(7):2562-7. DOI: 10.1182/blood-2003-02-0493. View

Gonzalez D, van der Burg M, Garcia-Sanz R, Fenton J, Langerak A, Gonzalez M . Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood. 2007; 110(9):3112-21. DOI: 10.1182/blood-2007-02-069625. View

Chiecchio L, Protheroe R, Ibrahim A, Cheung K, Rudduck C, Dagrada G . Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma. Leukemia. 2006; 20(9):1610-7. DOI: 10.1038/sj.leu.2404304. View

Lynch H, Thome S . Familial multiple myeloma. Blood. 2009; 114(4):749-50. DOI: 10.1182/blood-2009-03-207233. View

Vachon C, Kyle R, Therneau T, Foreman B, Larson D, Colby C . Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood. 2009; 114(4):785-90. PMC: 2716020. DOI: 10.1182/blood-2008-12-192575. View

Bizzaro N, Pasini P . Familial occurrence of multiple myeloma and monoclonal gammopathy of undetermined significance in 5 siblings. Haematologica. 1990; 75(1):58-63. View

Landgren O, Weiss B . Patterns of monoclonal gammopathy of undetermined significance and multiple myeloma in various ethnic/racial groups: support for genetic factors in pathogenesis. Leukemia. 2009; 23(10):1691-7. DOI: 10.1038/leu.2009.134. View

Bergsagel P, Kuehl W . Molecular pathogenesis and a consequent classification of multiple myeloma. J Clin Oncol. 2005; 23(26):6333-8. DOI: 10.1200/JCO.2005.05.021. View

Mostertz W, Stevenson M, Acharya C, Chan I, Walters K, Lamlertthon W . Age- and sex-specific genomic profiles in non-small cell lung cancer. JAMA. 2010; 303(6):535-43. DOI: 10.1001/jama.2010.80. View

10.

Leone P, Walker B, Jenner M, Chiecchio L, Dagrada G, Protheroe R . Deletions of CDKN2C in multiple myeloma: biological and clinical implications. Clin Cancer Res. 2008; 14(19):6033-41. PMC: 2581792. DOI: 10.1158/1078-0432.CCR-08-0347. View

11.

Terpos E, Katodritou E, Roussou M, Pouli A, Michalis E, Delimpasi S . High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents. Eur J Haematol. 2010; 85(2):114-9. DOI: 10.1111/j.1600-0609.2010.01466.x. View

12.

Walker B, Leone P, Jenner M, Li C, Gonzalez D, Johnson D . Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma. Blood. 2006; 108(5):1733-43. DOI: 10.1182/blood-2006-02-005496. View

13.

Purdue M, Lan Q, Menashe I, Zheng T, Zhang Y, Yeager M . Variation in innate immunity genes and risk of multiple myeloma. Hematol Oncol. 2010; 29(1):42-6. PMC: 2980579. DOI: 10.1002/hon.954. View

14.

Wisnivesky J, Halm E . Sex differences in lung cancer survival: do tumors behave differently in elderly women?. J Clin Oncol. 2007; 25(13):1705-12. DOI: 10.1200/JCO.2006.08.1455. View

15.

Walker B, Leone P, Chiecchio L, Dickens N, Jenner M, Boyd K . A compendium of myeloma-associated chromosomal copy number abnormalities and their prognostic value. Blood. 2010; 116(15):e56-65. DOI: 10.1182/blood-2010-04-279596. View

16.

Landgren O, Rajkumar S, Pfeiffer R, Kyle R, Katzmann J, Dispenzieri A . Obesity is associated with an increased risk of monoclonal gammopathy of undetermined significance among black and white women. Blood. 2010; 116(7):1056-9. PMC: 2938127. DOI: 10.1182/blood-2010-01-262394. View

17.

Lynch H, Ferrara K, Barlogie B, Coleman E, Lynch J, Weisenburger D . Familial myeloma. N Engl J Med. 2008; 359(2):152-7. PMC: 2775509. DOI: 10.1056/NEJMoa0708704. View

18.

Morgan G, Davies F, Gregory W, Cocks K, Bell S, Szubert A . First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010; 376(9757):1989-99. PMC: 3639680. DOI: 10.1016/S0140-6736(10)62051-X. View

19.

Hosgood 3rd H, Baris D, Zhang Y, Berndt S, Menashe I, Morton L . Genetic variation in cell cycle and apoptosis related genes and multiple myeloma risk. Leuk Res. 2009; 33(12):1609-14. PMC: 2749910. DOI: 10.1016/j.leukres.2009.03.013. View

20.

Landgren O, Kristinsson S, Goldin L, Caporaso N, Blimark C, Mellqvist U . Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. Blood. 2009; 114(4):791-5. PMC: 2716021. DOI: 10.1182/blood-2008-12-191676. View