J Cancer 2019; 10(3):577-582. doi:10.7150/jca.28905 This issue
1. Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Key Laboratory of Laboratory Medicine of Henan Province, Zhengzhou 450052, Henan , P.R. China
2. Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P.R.China.
3. Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, P.R.China
* These authors contributed equally to this work.
Multiple myeloma (MM) is an extremely complex plasma cell malignancy that is genetically heterogeneous. A recent Genome-wide association study (GWAS) indicated that variation at 2q22 (rs61070260) influences MM risk. This association has not been validated to date in a Chinese Han population. In this study, we evaluated the association between rs61070260 in LRP1B and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in LRP1B was significantly associated with MM susceptibility (P=3.937×10-37). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the LRP1B gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of LRP1B. For the SNP rs756168629 in exon 26, a missense mutation which results in a transition from arginine to histidine at position 1661 of the LRP1B protein, has not been found in Chinese populations according to the Chinese Millionome Database and Genome Aggregation Database (EAS), and this mutation was predicted to be deleterious or damaging by SIFT and PolyPhen. These findings firmly establish the role of LRP1B in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in LRP1B detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, LRP1B is likely to be a disease-associated gene that is implicated in the development and progression of MM.
Keywords: multiple myeloma, LRP1B, susceptibility, linkage disequilibrium, mutation