Association between the PARP1 Val762Ala polymorphism and cancer risk: evidence from 43 studies.
BACKGROUND
Poly (ADP-ribose) polymerase-1 (PARP-1) plays critical roles in the detection and repair of damaged DNA, as well as cell proliferation and death. Numerous studies have examined the associations between PARP1 Val762Ala (rs1136410 T>C) polymorphism and cancer susceptibility; nevertheless, the findings from different research groups remain controversial.


METHODS
We searched literatures from MEDLINE, EMBASE and CBM pertaining to such associations, and then calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using random-effects model. The false-positive report probability (FPRP) analysis was used to confirm the validity of significant findings. Moreover, potential effects of rs1136410 variants on PARP1 mRNA expression were analyzed for three ethnicities by combining data from HapMap (genotype) and SNPexp (mRNA expression).


RESULTS
The final meta-analysis incorporated 43 studies, consisting of 17,351 cases and 22,401 controls. Overall, our results did not suggest significant associations between Ala variant (Ala/Ala or Ala/Val genotype) and cancer risk. However, further stratification analysis showed significantly increased risk for gastric cancer (Ala/Ala vs. Val/Val: OR = 1.56, 95% CI = 1.01-2.42, Ala/Val vs. Val/Val: OR = 1.34, 95% CI = 1.14-1.58, dominant model: OR = 1.41, 95% CI = 1.21-1.65 and Ala vs. Val: OR = 1.29, 95% CI = 1.07-1.55). On the contrary, decreased risk for brain tumor (Ala/Val vs. Val/Val: OR = 0.77, 95% CI = 0.68-0.87, dominant model: OR = 0.77, 95% CI = 0.68-0.87 and Ala vs. Val: OR = 0.82, 95% CI = 0.74-0.91). Additionally, we found that the Ala carriers had a significantly increased risk in all models for Asians. Our mRNA expression data provided further biological evidence to consolidate this finding.


CONCLUSIONS
Despite some limitations, this meta-analysis found evidence for an association between the PAPR1 Val762Ala and cancer susceptibility within gastric cancer, brain tumor and Asian subgroups.
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Rui-Xi
RX
Hua
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
He-Ping
HP
Li
General Department of Internal Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yan-Bing
YB
Liang
Department of Molecular Epidemiology and Laboratory Medicine, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
Jin-Hong
JH
Zhu
Department of Nuclear Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Bing
B
Zhang
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Sheng
S
Ye
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Qiang-Sheng
QS
Dai
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Shi-Qiu
SQ
Xiong
Department of Thoracic Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yong
Y
Gu
Department of Urinary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Xiang-Zhou
XZ
Sun
D019943:Amino Acid Substitution / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors
D012333:RNA, Messenger; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases