A large study has revealed several genetic variations that may increase a person’s risk of developing multiple myeloma (MM).
The findings, published in Nature Communications, build on existing research that suggests MM can run in families.
“Our study expands our understanding of how inherited risk factors can influence the risk of myeloma,” said Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“We know that the inherited risk of myeloma does not come from just one or two major risk genes, as can be the case with breast cancer, but from multiple different genetic variants, each with only a small individual effect on risk. Identifying more of these variants gives us new insights into the potential causes of the disease and open up new strategies for prevention.”
For this study, Dr Houlston and his colleagues compared DNA from 9866 MM patients and 239,188 healthy adults.
This confirmed the association between MM and 9 previously reported single nucleotide polymorphisms (SNPs):
- rs6746082 at 2p23.3
- rs1052501 at 3p22.1
- rs4487645 at 7p15.3
- rs10936599 at 3q26.2
- rs2285803 at 6p21.3
- rs4273077 at 17p11.2
- rs877529 at 22q13.1
- rs56219066 at 5q15
- rs138740 at 22q13.
It also revealed 8 new SNPs that may increase the risk of MM:
- rs34229995 at 6p22.3 (P=1.31 × 10−8)
- rs9372120 at 6q21 (P=9.09 × 10−15)
- rs7781265 at 7q36.1 (P=9.71 × 10−9)
- rs1948915 at 8q24.21 (P=4.20 × 10−11)
- rs2811710 at 9p21.3 (P=1.72 × 10−13)
- rs2790457 at 10p12.1 (P=1.77 × 10−8)
- rs7193541 at 16q23.1 (P=5.00 × 10−12)
- rs6066835 at 20q13.13 (P=1.36 × 10−13).
These SNPs are located in regions of the genome involved in regulating genes linked to cell processes known to go wrong in MM development—namely, JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3, and PREX1.
This suggests that subtle effects on the activity of key genes could mean the proper development of plasma cells breaks down, increasing the likelihood of developing MM. However, as the researchers noted, further study is needed to confirm and better understand this phenomenon.
