Susceptibility genes and B-chronic lymphocytic leukaemia.
Common genetic variants are thought to increase the risk of chronic lymphocytic leukaemia (CLL), and case-control studies provide an approach to detect these variants. There have been multiple candidate gene studies published to date, but relatively few disease pathway studies or large genomic association studies. We summarize the results of these previous studies, as well as present results from our recent large pathway study of 9412 single nucleotide polymorphisms from 1253 immunity and inflammation genes in a study of 126 CLL cases and 484 frequency-matched controls. Several promising genes have been identified as susceptibility genes for risk of CLL across all of these association studies. However, a number of candidate gene studies have not been replicated in follow-up studies, whereas the results from disease pathway and large genomic studies have yet to be replicated in an independent sample. The challenge of future studies of this type will be overcoming study design issues, including definition of CLL, sample size limitations and multiple testing issues.
Slager
Susan L
SL
Division of Biostatistics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA. slager@mayo.edu
Kay
Neil E
NE
Fredericksen
Zachary S
ZS
Wang
Alice H
AH
Liebow
Mark
M
Cunningham
Julie M
JM
Vachon
Celine M
CM
Call
Timothy G
TG
Cerhan
James R
JR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide