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

Abstract

Summary 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 2,843 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.

Cancer statistics for African Americans, 2019

“…Elevated rates of obesity among blacks may contribute to their excess risk (Table ) . A family history of hematopoietic cancers is also associated with increased risk for MGUS and myeloma, with some studies finding a stronger association among blacks than whites . Immunobiological factors have been hypothesized to contribute to racial disparities as well …”

“…82 A family history of hematopoietic cancers is also associated with increased risk for MGUS and myeloma, with some studies finding a stronger association among blacks than whites. 83,84 Immunobiological factors have been hypothesized to contribute to racial disparities as well. 79 Myeloma death rates among blacks are approximately double those among whites (Table 5), largely reflecting higher incidence rates.…”

Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

“…Limitations include the lack of detailed information on clinical characteristics of MM at diagnosis, as well as information on family history of lymphohaematopoietic malignancies. Given that having a family history of these relatively rare malignancies is uncommon in the general population ( Schinasi et al , 2016 ), the potential for confounding by family history is likely to be minimal. However, further investigation in family-based studies and other studies with detailed clinical records may be informative.…”

Epidemiology of Multiple Myeloma

“…However, several reports during the past three decades [69][70][71][72][73] have analyzed the pattern of aggregation and pointed out a putative autosomal dominant mode of genetic transmission, reporting an excess familial risk for MM of about 2-to 4-fold and supporting a role for germline susceptibility genes, shared environmental influences, or an interaction of both. A variation in the presence of defining clinical features in MM patients according to family history of hematologic malignancy has been described [74,75]. MM showed an association with breast and prostate cancer, and colorectal cancer families, suggesting that MM shares genetic susceptibility with many cancers [76].…”