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

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Abstract

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.

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Acknowledgments

This work was supported by the Canadian Breast Cancer Foundation (CBCF) grant of Hilmi Ozcelik and by the Philippine Council for Health Research and Development grant-in-aid of Noel Pabalan. We thank Stephen Pisle, NCI Post-Baccalaureate Fellow of the National Institute of Health, USA.

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The authors declare that they have no competing interests

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Authors and Affiliations

  1. Office of Research and Development, Angeles University Foundation, Angeles City, Philippines

    Noel Pabalan

  2. Canadian Grain Commission, 5 Water Street, Winnipeg, MB, R3C 3G8, Canada

    Ofelia Francisco-Pabalan

  3. Ontario Ministry of the Environment, 125 Resources Road, Toronto, ON, M9P 3V6, Canada

    Hamdi Jarjanazi

  4. Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON, Canada

    Lillian Sung

  5. Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray St. Room L6-303, Box 29, Toronto, ON, M5T 3L9, Canada

    Hong Li & Hilmi Ozcelik

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  1. Noel Pabalan
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  4. Hong Li
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Correspondence to Hilmi Ozcelik.

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11033_2012_2009_MOESM1_ESM.doc

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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Pabalan, N., Francisco-Pabalan, O., Jarjanazi, H. et al. Racial and tissue-specific cancer risk associated with PARP1 (ADPRT) Val762Ala polymorphism: a meta-analysis. Mol Biol Rep 39, 11061–11072 (2012). https://doi.org/10.1007/s11033-012-2009-x

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