Oct312013

Potential Role of Lymphocyte Development Gene Variants in Non-Hodgkin Lymphoma Risk

The risk of developing NHL can be influenced by both environmental and genetic factors that play a role in the survival of lymphocytes. The contribution of genetic factors to NHL risk led Dr. Brooks-Wilson and colleagues to determine if genes associated with the important lymphocyte development components of immunity and inflammation, DNA damage repair, and programmed cell death play a role in NHL susceptibility.

New NHL cases in the greater Vancouver Regional District and Greater Victoria (Capital Regional District), British Columbia from March 2000 to February 2004 were asked to participate. 118 genes related to lymphocyte development processes were selected, tagged with single nucleotide polymorphisms (SNPs) and tested for association with NHL in 569 cases and 547 controls.

The results showed only one SNP, rs33003, showed significant association with susceptibility to diffuse large B-cell lymphoma (DLBCL), a subtype of NHL, after multiple rounds of testing. This SNP was located in the MSH3 gene, a DNA mismatch repair gene that has never before been linked with NHL. No evidence was found that a family history of colorectal cancer influences the association between rs33003 and DLCBL. They then tried to replicate these results in a population of patients in the San Francisco Bay area but were unfortunately unsuccessful.  The reason for this may have been that the MSH3 association occurs only in patients within specific DLBCL subgroups. Another possibility is that there are other true associations that exist but due to the small sample size, they were not detected in this study.

Therefore, there is still a huge opportunity for future research to explore the possible genetic factors that may contribute to NHL risk.

Reference:

Schuetz, J.M., Daley, D., Leach, S., Conde, L., Berry, B.R., Gallagher, R.P., Connors, J.M., Gascoyne, R.D., Bracci, P.M., Skibola, C.F., Spinelli, J.J., & Brooks-Wilson, A.R. (2013). Non-hodgkin lymphoma risk and variants in genes controlling lymphocyte development. PloS One, 8(9): e75170. http://www.ncbi.nlm.nih.gov/pubmed/24098683

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