Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.
We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.
Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. slager@mayo.edu
Susan L
SL
Slager
Christine F
CF
Skibola
Maria Chiara
MC
Di Bernardo
Lucia
L
Conde
Peter
P
Broderick
Shannon K
SK
McDonnell
Lynn R
LR
Goldin
Naomi
N
Croft
Amy
A
Holroyd
Shelley
S
Harris
Jacques
J
Riby
Daniel J
DJ
Serie
Neil E
NE
Kay
Timothy G
TG
Call
Paige M
PM
Bracci
Eran
E
Halperin
Mark C
MC
Lanasa
Julie M
JM
Cunningham
Jose F
JF
Leis
Vicki A
VA
Morrison
Logan G
LG
Spector
Celine M
CM
Vachon
Tait D
TD
Shanafelt
Sara S
SS
Strom
Nicola J
NJ
Camp
J Brice
JB
Weinberg
Estella
E
Matutes
Neil E
NE
Caporaso
Rachel
R
Wade
Martin J S
MJ
Dyer
Claire
C
Dearden
James R
JR
Cerhan
Daniel
D
Catovsky
Richard S
RS
Houlston
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D017404:In Situ Hybridization, Fluorescence; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000009:adverse effects*; D011379:Prognosis; D011446:Prospective Studies; D011743:Pyrimidines / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate