Journal des syndromes génétiques et de la thérapie génique
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Genetic Variability within ADA Gene and Endometrium Cancer

Gloria-Bottini F, Nicotra M, Benedetti-Panici PL, Pietropolli A, Saccucci P, Ambrosi S, Bottini E and Magrini A

Adenosine Deaminase (ADA) is a polymorphic enzyme that degrades irreversibly adenosine to inosine and
is present in cell cytoplasm and in interstitial fluid was it acts as ecto-ADA. Ecto-ADA shows also extra-enzymatic
activity acting as co- stimulatory molecule of adenosine receptors .Adenosine is a purine nucleoside that hasan
important role in cancer development.In solid tumors high level of this substance is determined by hypoxia resulting
in inhibition of T cell killer activation .
We have recently found an association between colon cancer and ADA genetic polymorphism. We studied three
polymorphic sites ADA1, ADA2 and ADA6 and found that ADA1 *2/ ADA2 *1 haplotype is more represented, while ADA1
*2/ ADA2 *2 is less represented in cancer than in controls. ADA2 *2/ ADA6 *2 is less represented in patients than in
controls. The present note reports a study in endometrium cancer.
We have studied 70 women with endometrium cancer from the White population of Rome.Data on 109 subjects
with colon cancer and on 246 blood donors reported in a previous paper are also shown.
The three polymorphisc sites of ADA gene (ADA1, ADA2 and ADA6) were analyzed. Genotypes were determined
by RFLP-PCR.
Statistical analyses were carried out by SPSS package. Haplotype frequencies are maximum likelihood
estimates.
No statistically significant difference is observed in the distribution of ADA haplotypes between the two cancers.
In both cancers ADA1 *2/ ADA2 *1 haplotype is more represented while ADA1 *2/ ADA2 *2 is less represented than
in controls. ADA2 *2/ ADA6 *2 haplotype is less represented in both cancers than in controls. A border line difference
between the two classes of cancers is observed in the distribution of ADA1/ADA6 haplotypes.
The present study was suggested by the following: i) High levels of adenosine in cancer inhibits T cell killer
activation, ii) ADA contributes to control level of adenosine, iii) Polymorphic sites of ADA may influence extraenzymatic
function of ecto-ADA. Our data confirm the association observed between ADA and colon cancer making
unlikely the possibility of a mere sampling chance artifact and suggest that genetic polymorphisms within the ADA
gene may have an important role in susceptibility to cancer.