Molecular Biology Reports

, Volume 39, Issue 12, pp 11061–11072 | Cite as

Racial and tissue-specific cancer risk associated with PARP1 (ADPRT) Val762Ala polymorphism: a meta-analysis

  • Noel Pabalan
  • Ofelia Francisco-Pabalan
  • Hamdi Jarjanazi
  • Hong Li
  • Lillian Sung
  • Hilmi Ozcelik


The Val762Ala polymorphism poly [ADP-ribose] polymerase 1 (PARP1) gene [ADPRT (adenosine diphosphate ribosyltransferase) gene] affects enzymatic activity, which modulates cancer susceptibility among human populations. Individual data on 13,745 cases and 16,947 controls from 28 published case–control studies were re-evaluated. Odds ratios (OR) were estimated for ethnic group, cancer type, smoking joint effects and studies confined to the Hardy–Weinberg equilibrium. We applied subgroup, sensitivity and outlier analyses as well as the Bonferroni correction for multiple testing. The results show strong evidence that the variant (C) allele confers significant increased risk in the Chinese (OR 1.20–1.44, P < 0.0001–0.002), exacerbated by smoking (OR 1.66–2.53, P < 0.0001) and joint interaction with XRCC1 Arg399Gln (OR 1.39, P < 0.0001) as well as adjustment for tumor type (gastric carcinoma ORs 1.39–2.01, P < 0.0001). These significant effects were unaltered following conservative correction for multiple tests. By contrast, this procedure erased the protective significance in Caucasians, but not in two American subgroups, (i) those in the brain tumor category (0.77–0.79, P < 0.0001) and (ii) smokers in the dominant model (OR 0.86, P < 0.0001). These differential findings between the two ethnicities maybe correlated with significantly (P < 0.0001) greater allele frequency of the variant allele (C) among the Chinese compared to Caucasians. Our racial and tissue-specific summary estimates imply consideration of the Val762Ala polymorphism as candidate gene marker for screening cancer patients’ best suited for PARP inhibitor therapy.


Cancer ADPRT PARP1 Polymorphism Val762Ala Meta-analysis 

Supplementary material

11033_2012_2009_MOESM1_ESM.doc (724 kb)
Figure S1 Frequencies of the variant allele PARP1 Val762Ala polymorphism of control subjects Figure S2a Galbraith plot analysis to evaluate heterogeneity in the Chinese Figure S2b Galbraith plot analysis to evaluate heterogeneity in Caucasians (DOC 724 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Noel Pabalan
    • 1
  • Ofelia Francisco-Pabalan
    • 2
  • Hamdi Jarjanazi
    • 3
  • Hong Li
    • 5
  • Lillian Sung
    • 4
  • Hilmi Ozcelik
    • 5
  1. 1.Office of Research and DevelopmentAngeles University FoundationAngeles CityPhilippines
  2. 2.Canadian Grain CommissionWinnipegCanada
  3. 3.Ontario Ministry of the EnvironmentTorontoCanada
  4. 4.Division of Hematology/OncologyHospital for Sick ChildrenTorontoCanada
  5. 5.Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research InstituteMount Sinai HospitalTorontoCanada

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