Familial predisposition and genetic risk factors for lymphoma.
James R CerhanSusan L SlagerPublished in: Blood (2015)
Our understanding of familial predisposition to lymphoma (collectively defined as non-Hodgkin lymphoma [NHL], Hodgkin lymphoma [HL], and chronic lymphocytic leukemia [CLL]) outside of rare hereditary syndromes has progressed rapidly during the last decade. First-degree relatives of NHL, HL, and CLL patients have an ∼1.7-fold, 3.1-fold, and 8.5-fold elevated risk of developing NHL, HL, and CLL, respectively. These familial risks are elevated for multiple lymphoma subtypes and do not appear to be confounded by nongenetic risk factors, suggesting at least some shared genetic etiology across the lymphoma subtypes. However, a family history of a specific subtype is most strongly associated with risk for that subtype, supporting subtype-specific genetic factors. Although candidate gene studies have had limited success in identifying susceptibility loci, genome-wide association studies (GWAS) have successfully identified 67 single nucleotide polymorphisms from 41 loci, predominately associated with specific subtypes. In general, these GWAS-discovered loci are common (minor allele frequency >5%), have small effect sizes (odds ratios, 0.60-2.0), and are of largely unknown function. The relatively low incidence of lymphoma, modest familial risk, and the lack of a screening test and associated intervention, all argue against active clinical surveillance for lymphoma in affected families at this time.
Keyphrases
- genome wide
- diffuse large b cell lymphoma
- chronic lymphocytic leukemia
- genome wide association
- risk factors
- hodgkin lymphoma
- early onset
- copy number
- randomized controlled trial
- end stage renal disease
- genome wide association study
- dna methylation
- ejection fraction
- chronic kidney disease
- public health
- prognostic factors
- peritoneal dialysis
- gene expression
- human health