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Meta-Analysis
. 2016 Oct;175(1):87-101.
doi: 10.1111/bjh.14199. Epub 2016 Jun 22.

Multiple myeloma and family history of lymphohaematopoietic cancers: Results from the International Multiple Myeloma Consortium

Leah H Schinasi  1 , Elizabeth E Brown  2 , Nicola J Camp  3 , Sophia S Wang  4 , Jonathan N Hofmann  5 , Brian C Chiu  6 , Lucia Miligi  7 , Laura E Beane Freeman  5 , Silvia de Sanjose  8 , Leslie Bernstein  4 , Alain Monnereau  9   10 , Jacqueline Clavel  9   10 , Guido J Tricot  11 , Djordje Atanackovic  3 , Pierluigi Cocco  12 , Laurent Orsi  9   10 , James A Dosman  13 , John R McLaughlin  14 , Mark P Purdue  5 , Wendy Cozen  15 , John J Spinelli  16 , Anneclaire J de Roos  17
Affiliations
Meta-Analysis

Multiple myeloma and family history of lymphohaematopoietic cancers: Results from the International Multiple Myeloma Consortium

Leah H Schinasi et al. Br J Haematol. 2016 Oct.

Abstract

Family clusters of multiple myeloma (MM) suggest disease heritability. Nevertheless, patterns of inheritance and the importance of genetic versus environmental risk factors in MM aetiology remain unclear. We pooled data from eleven case-control studies from the International Multiple Myeloma Consortium to characterize the association of MM risk with having a first-degree relative with a history of a lympho-haematapoietic cancer. Unconditional logistic regression models, adjusted for study, sex, age and education level, were used to estimate associations between MM risk and having a first-degree relative with a history of non-Hodgkin lymphoma, Hodgkin lymphoma, leukaemia or MM. Sex, African American race/ethnicity and age were explored as effect modifiers. A total of 2843 cases and 11 470 controls were included. MM risk was elevated in association with having a first-degree relative with any lympho-haematapoietic cancer (Odds Ratio (OR) = 1·29, 95% Confidence Interval (CI): 1·08-1·55). The association was particularly strong for having a first-degree relative with MM (OR = 1·90, 95% CI: 1·26-2·87), especially among men (OR = 4·13, 95% CI: 2·17-7·85) and African Americans (OR = 5·52, 95% CI: 1·87-16·27).These results support the hypothesis that genetic inheritance plays a role in MM aetiology. Future studies are warranted to characterize interactions of genetic markers with environmental exposures.

Keywords: epidemiology; family history; lympho-haematopoietic malignancies; lymphoma; multiple myeloma.

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Figures

Figure 1
Figure 1
Forest plot showing study-specific and pooled odds ratio (OR, diamond) estimates (95% confidence interval, CI, indicated by the horizontal line) of association between multiple myeloma risk and having a first-degree relative with a history of a lymphohaematopoietic cancer. All models were adjusted for sex, age (coded using a linear and quadratic terms) and education (< high school versus high school or more). The pooled OR estimates were also adjusted for study. Abbreviations: iMAGE, Molecular and Genetic Epidemiology Study of Myeloma; LACCMM, Los Angeles County Case Control Multiple Myeloma Study; USC, University of Southern California.
Figure 2
Figure 2
Forest plots showing study-specific and pooled odds ratio (OR, diamond) estimates (95% confidence interval, CI, indicated by the horizontal line) of association between multiple myeloma and having a first-degree relative with a history of: A) multiple myeloma, B) NHL, C) leukaemia and D) Hodgkin lymphoma. All models were adjusted for sex, age (coded using a linear and quadratic terms) and education (< high school versus high school or more). The pooled OR estimates were also adjusted for study. Abbreviations: NHL, non Hodgkin lymphoma; NE, Not estimable; iMAGE, Molecular and Genetic Epidemiology Study of Myeloma; LACCMM, Los Angeles County Case Control Multiple Myeloma Study; USC, University of Southern California.
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