Cyclin D1 C.870G>a Polymorphism in Patients with Multiple Myeloma after Allogeneic Stem Cells Transplantation

Introduction: Over the last decade, the cyclin D1 (CCND1) c.870G>A polymorphism has been variously reported to confer risk for a large number of cancers. Deregulation of a D-group cyclin is a key feature of multiple myeloma (MM). Previously published meta-analysis shown a relationship between CCND1 c.870G>A and risk of t(11;14) in MM (Wienhold, 2013). Allogeneic stem cell transplantation (AlloSCT) is a potential curative treatment for MM patients. There are no data with regard to the role of CCND1 c.870G>A polymorphism in stem cells donors and outcome of transplantation in MM patients.

Methods: In this study we developed an endonuclease restriction method to identify CCND1 c.870G>A polymorphism. Directly Sanger sequencing were used to confirm the results.

Results: At first, we analyzed 130 MM patients and 100 healthy donors as a control. CCND1 c.870G>A polymorphism was strongly associated with the t(11;14)(q13;q32) (P<0.001). In addition, we have analyzed CCND1 c.870G>A polymorphism 55 pairs of MM patients and their allogeneic stem cell donors, retrospectively. Interestingly, c.870G-genotype in related and unrelated donors was statistically correlated with poor outcome after AlloSCT (P<0.01). Moreover, only patients transplanted with “G-Genotype” donors developed secondary cancer after AlloSCT (P<0.01). No secondary tumors were diagnosed in the group of MM patients received grafts from “A-, AG-genotype” donors.

Conclusion: Our data suggest the published data that constitutive genetic factor (CCND1 c.870 G>A polymorphism) is associated with a specific chromosomal translocation in patients with MM. Despite the fact that our group of patients after AlloSCT is small, we found a statistical association between the c.870G-genotype in donor and a poor prognosis after transplantation.