Common Variants in the PALB2 Gene Confer Susceptibility to Breast Cancer: a Meta-analysis

  • Zhang, Yi-Xia (Department of Ultrasonography, the First Affiliated Hospital of China Medical University) ;
  • Wang, Xue-Mei (Department of Ultrasonography, the First Affiliated Hospital of China Medical University) ;
  • Kang, Shu (Department of Ultrasonography, the First Affiliated Hospital of China Medical University) ;
  • Li, Xiang (Department of Ultrasonography, the First Affiliated Hospital of China Medical University) ;
  • Geng, Jing (Department of Ultrasonography, the First Affiliated Hospital of China Medical University)
  • Published : 2013.12.31


Objective: Increasing scientific evidence suggests that common variants in the PALB2 gene may confer susceptibility to breast cancer, but many studies have yielded inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationship between PALB2 genetic variants and breast cancer risk. Methods: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI and CBM databases from their inception through September 1st, 2013. A meta-analysis was performed using the STATA 12.0 software and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Six case-control studies were included with a total of 4,499 breast cancer cases and 6,369 healthy controls. Our meta-analysis reveals that PALB2 genetic variants may increase the risk of breast cancer (allele model: OR>1.36, 95%CI: 1.20~1.52, P < 0.001; dominant model: OR>1.64, 95%CI: 1.42~1.91, P < 0.001; respectively). Subgroup analyses by ethnicity indicated PALB2 genetic variants were associated with an increased risk of breast cancer among both Caucasian and Asian populations (all P < 0.05). No publication bias was detected in this meta-analysis (all P > 0.05). Conclusion: The current meta-analysis indicates that PALB2 genetic variants may increase the risk of breast cancer. Thus, detection of PALB2 genetic variants may be a promising biomarker approach.


  1. Benson JR, Jatoi I (2012). The global breast cancer burden. Future Oncol, 8, 697-702.
  2. Bogdanova N, Sokolenko AP, Iyevleva AG, et al (2011). PALB2 mutations in German and Russian patients with bilateral breast cancer. Breast Cancer Res Treat, 126, 545-50.
  3. Bray F, Jemal A, Grey N, et al (2012). Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol, 13, 790-801.
  4. Cao AY, Huang J, Hu Z, et al (2009). The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives. Breast Cancer Res Treat, 114, 457-62.
  5. Cao AY, Yu KD, Yin WJ, et al (2010). Five common single nucleotide polymorphisms in the PALB2 gene and susceptibility to breast cancer in eastern Chinese population. Breast Cancer Res Treat, 123, 133-8.
  6. Casadei S, Norquist BM, Walsh T, et al (2011). Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res, 71, 2222-9.
  7. Chen P, Liang J, Wang Z, et al (2008). Association of common PALB2 polymorphisms with breast cancer risk: a case-control study. Clin Cancer Res, 14, 5931-7.
  8. Colditz GA, Kaphingst KA, Hankinson SE, et al (2012). Family history and risk of breast cancer: nurses' health study. Breast Cancer Res Treat, 133, 1097-104.
  9. Dupont WD and Plummer WD, Jr. (1990). Power and sample size calculations. A review and computer program. Control Clin Trials, 11, 116-28.
  10. Eeles RA, Olama AA, Benlloch S, et al (2013). Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet, 45, 385-91, 91e1-2.
  11. Erkko H, Xia B, Nikkila J, et al (2007). A recurrent mutation in PALB2 in Finnish cancer families. Nature, 446, 316-9.
  12. Frankenberg-Schwager M and Gregus A (2012). Chromosomal instability induced by mammography X-rays in primary human fibroblasts from BRCA1 and BRCA2 mutation carriers. Int J Radiat Biol, 88, 846-57.
  13. Guenard F, Pedneault CS, Ouellette G, et al (2010). Evaluation of the contribution of the three breast cancer susceptibility genes CHEK2, STK11, and PALB2 in non-BRCA1/2 French Canadian families with high risk of breast cancer. Genet Test Mol Biomarkers, 14, 515-26.
  14. Heikkinen T, Karkkainen H, Aaltonen K, et al (2009). The breast cancer susceptibility mutation PALB2 1592delT is associated with an aggressive tumor phenotype. Clin Cancer Res, 15, 3214-22.
  15. Hellebrand H, Sutter C, Honisch E, et al (2011). Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer. Hum Mutat, 32, E2176-88.
  16. Jackson D, White IR and Riley RD (2012). Quantifying the impact of between-study heterogeneity in multivariate metaanalyses. Stat Med, 31, 3805-20.
  17. Kuusisto KM, Bebel A, Vihinen M, et al (2011). Screening for BRCA1, BRCA2, CHEK2, PALB2, BRIP1, RAD50, and CDH1 mutations in high-risk Finnish BRCA1/2-founder mutation-negative breast and/or ovarian cancer individuals. Breast Cancer Res, 13, R20.
  18. Llanos AA, Dumitrescu RG, Marian C, et al (2012). Adipokines in plasma and breast tissues: associations with breast cancer risk factors. Cancer Epidemiol Biomarkers Prev, 21, 1745-55.
  19. O'Donovan PJ and Livingston DM (2010). BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis, 31, 961-7.
  20. Pern F, Bogdanova N, Schurmann P, et al (2012). Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospitalbased series of German patients with triple-negative breast cancer. PLoS One, 7, e47993.
  21. Peters JL, Sutton AJ, Jones DR, et al (2006). Comparison of two methods to detect publication bias in meta-analysis. JAMA, 295, 676-80.
  22. Rahman N, Seal S, Thompson D, et al (2007). PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nat Genet, 39, 165-7.
  23. Siaud N, Barbera MA, Egashira A, et al (2011). Plasticity of BRCA2 function in homologous recombination: genetic interactions of the PALB2 and DNA binding domains. PLoS Genet, 7, e1002409.
  24. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25, 603-5.
  25. Stephens PJ, Tarpey PS, Davies H, et al (2012). The landscape of cancer genes and mutational processes in breast cancer. Nature, 486, 400-4.
  26. Teo ZL, Provenzano E, Dite GS, et al (2013). Tumour morphology predicts PALB2 germline mutation status. Br J Cancer, 109, 154-63.
  27. Xia B, Sheng Q, Nakanishi K, et al (2006). Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2. Mol Cell, 22, 719-29.
  28. Zintzaras E, Ioannidis JP (2005). HEGESMA: genome search meta-analysis and heterogeneity testing. Bioinformatics, 21, 3672-3.

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