PMID- 26474455
OWN - NLM
STAT- MEDLINE
DCOM- 20161026
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 34
DP  - 2015 Nov 3
TI  - Genetic polymorphisms associated with increased risk of developing chronic 
      myelogenous leukemia.
PG  - 36269-77
LID - 10.18632/oncotarget.5915 [doi]
AB  - Little is known about inherited factors associated with the risk of developing 
      chronic myelogenous leukemia (CML). We used a dedicated DNA chip containing 16 
      561 single nucleotide polymorphisms (SNPs) covering 1 916 candidate genes to 
      analyze 437 CML patients and 1 144 healthy control individuals. Single SNP 
      association analysis identified 139 SNPs that passed multiple comparisons (1% 
      false discovery rate). The HDAC9, AVEN, SEMA3C, IKBKB, GSTA3, RIPK1 and FGF2 
      genes were each represented by three SNPs, the PSM family by four SNPs and the 
      SLC15A1 gene by six. Haplotype analysis showed that certain combinations of rare 
      alleles of these genes increased the risk of developing CML by more than two or 
      three-fold. A classification tree model identified five SNPs belonging to the 
      genes PSMB10, TNFRSF10D, PSMB2, PPARD and CYP26B1, which were associated with CML 
      predisposition. A CML-risk-allele score was created using these five SNPs. This 
      score was accurate for discriminating CML status (AUC: 0.61, 95%CI: 0.58-0.64). 
      Interestingly, the score was associated with age at diagnosis and the average 
      number of risk alleles was significantly higher in younger patients. The 
      risk-allele score showed the same distribution in the general population (HapMap 
      CEU samples) as in our control individuals and was associated with differential 
      gene expression patterns of two genes (VAPA and TDRKH). In conclusion, we 
      describe haplotypes and a genetic score that are significantly associated with a 
      predisposition to develop CML. The SNPs identified will also serve to drive 
      fundamental research on the putative role of these genes in CML development.
FAU - Bruzzoni-Giovanelli, Heriberto
AU  - Bruzzoni-Giovanelli H
AD  - Universite Paris Diderot, Sorbonne Paris Cite UMRS 1160 INSERM, Paris, France.
AD  - Centre d'Investigations Cliniques 9504 INSERM-AP-HP Hopital Saint-Louis, Paris, 
      France.
FAU - Gonzalez, Juan R
AU  - Gonzalez JR
AD  - Centre de Recerca en Epidemiologia Ambiental (CREAL), Barcelona, Spain.
AD  - Institut Municipal d'Investigacio Medica (IMIM), Barcelona, Spain.
AD  - CIBER Epidemiologia y Salud Publica (CIBERESP), Spain Centre de Recerca en 
      Epidemiologia Ambiental (CREAL), Barcelona, Spain.
FAU - Sigaux, Francois
AU  - Sigaux F
AD  - Institut Universitaire d'Hematologie, Universite Paris Diderot, Sorbonne Paris 
      Cite, Paris, France.
FAU - Villoutreix, Bruno O
AU  - Villoutreix BO
AD  - Universite Paris Diderot, Sorbonne Paris Cite UMRS 973 Inserm, Paris, France/ 
      Inserm, U973, Paris, France.
FAU - Cayuela, Jean Michel
AU  - Cayuela JM
AD  - Laboratoire Central d'Hematologie, Hopital Saint Louis, Paris, France.
AD  - EA3518, Universite Paris Diderot, Sorbonne Paris Cite, Paris, France.
FAU - Guilhot, Joelle
AU  - Guilhot J
AD  - Inserm CIC 0802, CHU de Poitiers, Poitiers, France.
FAU - Preudhomme, Claude
AU  - Preudhomme C
AD  - Laboratoire d'Hematologie, Inserm, U837, CHRU, Lille, France/Universite de Lille 
      Nord, Institut de Recherche sur le Cancer de Lille, Lille, France.
FAU - Guilhot, Francois
AU  - Guilhot F
AD  - Inserm CIC 0802, CHU de Poitiers, Poitiers, France.
FAU - Poyet, Jean-Luc
AU  - Poyet JL
AD  - Universite Paris Diderot, Sorbonne Paris Cite UMRS 1160 INSERM, Paris, France.
FAU - Rousselot, Philippe
AU  - Rousselot P
AD  - Service d'Hematologie et d'Oncologie, Hopital Mignot, Universite Versailles, 
      Saint-Quentin-en-Yvelines, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT00219739
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
SB  - IM
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
PMC - PMC4742176
OTO - NOTNLM
OT  - CML
OT  - SNPs
OT  - genetic predisposition
OT  - myeloid leukemia
COIS- CONFLICTS OF INTEREST All the authors read and approved the final manuscript and 
      declare no conflicts of interest.
EDAT- 2015/10/17 06:00
MHDA- 2016/10/27 06:00
PMCR- 2015/11/03
CRDT- 2015/10/17 06:00
PHST- 2015/08/12 00:00 [received]
PHST- 2015/09/14 00:00 [accepted]
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2016/10/27 06:00 [medline]
PHST- 2015/11/03 00:00 [pmc-release]
AID - 5915 [pii]
AID - 10.18632/oncotarget.5915 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Nov 3;6(34):36269-77. doi: 10.18632/oncotarget.5915.