PMID- 20012387
OWN - NLM
STAT- MEDLINE
DCOM- 20101122
LR  - 20240209
IS  - 1466-1268 (Electronic)
IS  - 1355-8145 (Print)
IS  - 1355-8145 (Linking)
VI  - 15
IP  - 5
DP  - 2010 Sep
TI  - HLA complex-linked heat shock protein genes and childhood acute lymphoblastic 
      leukemia susceptibility.
PG  - 475-85
LID - 10.1007/s12192-009-0161-6 [doi]
AB  - Three heat shock protein 70 (HSP70) genes, HSPA1L, HSPA1A, and HSPA1B, are 
      located within the human leukocyte antigen (HLA) class III region. HSPs act as 
      stress signals and regulate natural killer cell response to cancer. HSP70 gene 
      polymorphisms show disease associations partly due to their linkage 
      disequilibrium with HLA alleles. To systematically evaluate their associations 
      with childhood acute lymphoblastic leukemia (ALL), we examined the three 
      functional single nucleotide polymorphisms (SNPs) rs2227956 (T493M) in HSPA1L, 
      rs1043618 in HSPA1A 5'UTR, and rs1061581 (Q351Q) in HSPA1B by TaqMan assays or 
      polymerase chain reaction-restriction fragment length polymorphism in 114 ALL 
      cases and 414 controls from Wales (UK), in 100 Mexican Mestizo ALL cases and 253 
      controls belonging to the same ethnic group, and in a panel of 82 HLA-typed 
      reference cell line samples. Homozygosity for HSPA1B rs1061581 minor allele G was 
      associated with protection (odds ratio (OR) = 0.37, 95% confidence interval (CI) 
      = 0.16-0.78; P = 0.007) with gene-dosage effect (additive model) reaching 
      significance (P = 0.0001) in the Welsh case-control group. This association was 
      replicated in the second case-control group from Mexico (OR (recessive model) = 
      0.49, 95% CI = 0.24-0.96; P = 0.03), and the pooled analysis yielded a strong 
      association (Mantel-Haenszel OR = 0.43, 95% CI = 0.27-0.69, P = 0.0004). The 
      association was stronger in males in each group and in the pooled analysis. A 
      three-SNP haplotype including the major allele A of rs1061581 showed a highly 
      significant increase in Welsh cases compared with respective controls (6.7% vs 
      1.8%; P = 0.0003) due to the difference between male cases and controls. The 
      protective allele of rs1061581 occurred more frequently on the HLA-DRB3 
      haplotypes (especially DRB1*03) in the cell line panel, but the HSPA1B 
      association was independent from the HLA-DRB4 association previously detected in 
      the same case-control group from Wales (adjusted P = 0.001). Given the cancer 
      promoting roles played by HSPs intracellularly as well as roles in immune 
      surveillance when expressed on the cell surface and the known correlations 
      between expression levels and the HSP polymorphisms, these results are likely to 
      indicate a primary association and warrant detailed assessment in childhood ALL 
      development.
FAU - Ucisik-Akkaya, Esma
AU  - Ucisik-Akkaya E
AD  - Genomic Immunoepidemiology Laboratory, HUMIGEN LLC, The Institute for Genetic 
      Immunology, 2439 Kuser Road, Hamilton, NJ 08690-3303, USA.
FAU - Davis, Charronne F
AU  - Davis CF
FAU - Gorodezky, Clara
AU  - Gorodezky C
FAU - Alaez, Carmen
AU  - Alaez C
FAU - Dorak, M Tevfik
AU  - Dorak MT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091209
PL  - Netherlands
TA  - Cell Stress Chaperones
JT  - Cell stress & chaperones
JID - 9610925
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (HSPA1A protein, human)
RN  - 0 (HSPA1B protein, human)
RN  - 0 (HSPA1L protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Female
MH  - Genetic Predisposition to Disease/genetics
MH  - Genotype
MH  - HSP70 Heat-Shock Proteins/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Polymorphism, Restriction Fragment Length/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics
MH  - Sex Factors
PMC - PMC3006629
EDAT- 2009/12/17 06:00
MHDA- 2010/12/14 06:00
PMCR- 2011/03/01
CRDT- 2009/12/17 06:00
PHST- 2009/07/20 00:00 [received]
PHST- 2009/11/16 00:00 [accepted]
PHST- 2009/11/14 00:00 [revised]
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - S1355-8145(23)00570-9 [pii]
AID - 161 [pii]
AID - 10.1007/s12192-009-0161-6 [doi]
PST - ppublish
SO  - Cell Stress Chaperones. 2010 Sep;15(5):475-85. doi: 10.1007/s12192-009-0161-6. 
      Epub 2009 Dec 9.