Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #8

Lightning Talks Abstract
------------------------






Presenter's First Name: : Erman









Presenter's Last Name:: Akkus









Title (eg: professor, assistant professor, chair, etc):: MD









Degree(s): MD, Internal Medicine Specialisst, Medical Oncology Fellow









Contact Email:: erman_akkus@yahoo.com









Organization:: Ankara University Faculty of Medicine, Department of Medical Oncology, Ankara, Türkiye









Project Title:: A Germline Variant of BNIP1 Gene (rs28199) is Associated with Familial Multiple Myeloma 









Additional Authors:
1. First Name: Timur
   Last Name: Tuncalı
   Degree(s): MD
   Organization: Department of Medical Genetics, Ankara University Faculty of Medicine, Ankara, Turkey
2. First Name: Hasan Yalım
   Last Name: Akın
   Degree(s): PhD
   Organization: Department of Hematology, Ankara University, Faculty of Medicine, Ankara, Türkiye
3. First Name: Ayşe 
   Last Name: Salihoğlu
   Degree(s): MD
   Organization: Department of Hematology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Türkiye
4. First Name: Ömür Gökmen
   Last Name: Sevindik
   Degree(s): MD
   Organization: Department of Hematology, Medipol University, Faculty of Medicine, Istanbul, Türkiye
5. First Name: Hakkı Onur
   Last Name: Kırkızlar
   Degree(s): MD
   Organization: Department of Hematology, Trakya University Faculty of Medicine, Edirne, Türkiye
6. First Name: Siret
   Last Name: Ratip
   Degree(s): MD
   Organization: Department of Hematology, Acibadem Healthcare Group, Istanbul, Türkiye
7. First Name: Sevgi
   Last Name: Kalayoğlu Beşışık
   Degree(s): MD
   Organization: Department of Internal Medicine, Division of Hematology, Istanbul University Medical Faculty, Istanbul, Türkiye
8. First Name: Sibel
   Last Name: Kabukçu Hacıoğlu
   Degree(s): MD
   Organization: Department of Hematology, Pamukkale University Faculty of Medicine, Denizli, Türkiye
9. First Name: Güldane
   Last Name: Cengiz Seval
   Degree(s): MD
   Organization: Department of Hematology, Ankara University, Faculty of Medicine, Ankara, Türkiye
10. First Name: Meral
    Last Name: Beksaç
    Degree(s): MD
    Organization: Department of Hematology, Ankara Liv Hospital, Istinye University, Ankara, Türkiye










Abstract::
Background: A variant in the BNIP1 gene (rs28199) has been reported to be associated with multiple myeloma (MM) risk (Macauda et al., Interlymph-Heidelberg Consortium). We have recently reported that this variant is present in 13 of 18 familial MM cases (72.2%). In this study, we expanded our familial cases to analyze the rs28199 variant and aimed to compare it to non-familial MM and healthy populations.

Methods: A total of 32 familial MM and 30 non-familial MM cases were included in the study from hematology centers in Türkiye. Targeted NGS sequencing was utilized to investigate the germline variant from patients’ peripheral blood samples. Allele frequencies of the study group were compared to the Türkiye Genome Project data.

Results: 65.6% (n=21) of the familial and 40% (n=12) of the non-familial MM cases were positive for the BNIP1 variant, revealing a significant association between the variant and familial MM (OR: 2.86 (95% CI: 1.02-8.04), p=0.04). Among the variant-positive patients, the rates of homozygosity were 47.6% (n=12) in the familial and 8.3% (n=1) in the non-familial MM cases (OR: 10, (95% CI: 1.08-91.98), p=0.02). The variant allele frequencies were 0.48 and 0.22 in familial and non-familial MM cases, respectively (p=0.00). Likewise, rs28199 allele frequency among familial MM cases was also more frequent than the frequency observed within germline whole genome data of healthy population (0.48 vs 0.32, p=0.02).

Conclusion: This study shows that the germline BNIP1 variant (rs28199) when particularly in a homozygous state, is associated with familial MM.