Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
Using EpiLymph case-control data, we found that chronic lymphocytic leukemia patients were more likely to have abnormal reactive serological patterns to Epstein Barr virus than controls. Here, we aimed to assess whether this association is modified by genetic variants. We examined 1,305 Single Nucleotide Polymorphisms from 300 selected genes related to various pathways in 240 cases and 513 controls from five European centers. In a recessive model, patients positive to aberrant antibody pattern and homozygous for rare genotypes in rs8113877T>G or rs17576A>G of the MMP9 gene were at highest risk of chronic lymphocytic leukemia. In a dominant model, TP73 showed the highest risk in patients positive to aberrant antibody pattern and homozygous for the wild-type genotype in rs1885859G>C or rs3765701A>T. All interactions were additive and no main effect was observed. The strong interactions observed may be indicative of a specific pathway in cancer genesis. Confirmation of these results is warranted.
Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain. dcasabonne@iconcologia.net
Delphine
D
Casabonne
Oscar
O
Reina
Yolanda
Y
Benavente
Nikolaus
N
Becker
Marc
M
Maynadié
Lenka
L
Foretová
Pierluigi
P
Cocco
Anna
A
González-Neira
Alexandra
A
Nieters
Paolo
P
Boffetta
Jaap M
JM
Middeldorp
Silvia
S
de Sanjose
D016022:Case-Control Studies; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D015996:Survival Rate; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D020780:Matrix Metalloproteinase 9