PHG Foundation | Genetic loci associated with Hodgkin's lymphoma

Genetic loci associated with Hodgkin's lymphoma
Analysis of a study published in a science journal | By Dr Gurdeep Sagoo | Published 3 November 2010

Study: A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3).
By: Enciso-Mora V. et al. (45 authors total)
In: Nature Genetics
Link: http://dx.doi.org/10.1038/ng.696

What this study set out to do:
To identify genetic loci associated with susceptibility to classical Hodgkin's lymphoma (cHL).

How they went about it:
The researchers performed a two-stage genome-wide association study (GWAS) comparing around 500,000 SNPs in 589 patients with cHL and 5,199 controls. Initial findings were then followed-up in an additional 524 cases and 1,533 controls with further replication work in 1,533 cases and 1,883 controls from three independent studies.

Outcome:
The study confirmed the role of the immune system in susceptibility to cHL, with several associations noted within the HLA region on chromosome 6. Three novel associations on chromosomes 2, 8, and 10 were also identified following a combined analysis of all data including the replication studies, implicating the REL and GATA3 genes on chromosomes 2 and 10. The region of interest on chromosome 8 contains several genes previously linked with other cancers such as those of the prostate and breast.

Conclusion:
The authors conclude that there is a sound biological basis for association between all the genetic regions implicated in their study and risk of cHL. This includes evidence for a relationship between the three novel regions, although the authors were only able to detect nominal interactions between the HLA region and chromosome 2 regions, and between chromosomes 8 and 10. They also acknowledge that “further studies are needed to investigate possible interactions between these susceptibility loci and their interplay with EBV [Epstein Barr virus] infection” and state that “the modest size of our study makes it likely that further risk variants for cHL can be identified through additional studies.”

Our view:
Despite being limited in size, this study has identified several very biologically interesting susceptibility loci and new insights on the genetic basis of Hodgkin's lymphoma. Although the Epstein Barr virus infection may be causally related to some cases of cHL, the etiology of EBV-negative cases is still largely unknown despite extensive research. The findings on chromosomes 2, 6, and 8 in this study were further enriched in EBV-negative cases, which suggests that these regions may be involved in disease etiology via a different pathway from that followed by EBV infection. This could lead to exciting follow-up work

PHG Foundation | Genetic loci associated with Hodgkin's lymphoma