A genome screen of families at high risk for Hodgkin lymphoma: evidence for a susceptibility gene on chromosome 4

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Abstract
It is not known whether or how extrinsic risk factors interact with genetic susceptibility. Identifying inherited susceptibility genes is an important step towards defining the pathway(s) leading to development of HL and understanding its complex aetiology. There have been many studies of somatic mutations in HL tumour cells, but although there are associations with HLA types, specific germline genes causing susceptibility have not yet been identified. Early studies of HLA Class I alleles in familial HL showed increased haplotype sharing among affected sibling pairs.16,17 We have previously conducted studies of HLA Class II loci in 16 high risk HL families and found that alleles reported to be associated in case–control studies (such as DRB1*1501 and DQB1*0602) were also associated with familial HL using a family based analytical approach.18 There have been no comprehensive searches of the genome for HL genes, largely due to the difficulty in assembling informative samples. Even though this tumour is strongly familial, the proportion of cases with a family history is small, and affected families typically have very few cases.

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