Int J Med Sci 2011; 8(6):492-500. doi:10.7150/ijms.8.492

Research Paper

Translational Medicine and Reliability of Single-Nucleotide Polymorphism Studies: Can We Believe in SNP Reports or Not?

Antonis Valachis1,2, Davide Mauri2,3,✉, Christodoulos Neophytou2, Nikolaos P. Polyzos2,4, Lampriani Tsali5, Antonios Garras6, Evangelos G. Papanikolau4

1. Onkologkliniken Sörmland, Mälarsjukhuset, Eskilstuna, Sweden
2. PACMeR, department of. Medical Oncology, Athens, Greece
3. Department of Medical Oncology, General Hospital of Lamia, Greece
4. Centre for Reproductive Medicine, Free University of Brussels, Brussels, Belgium
5. PACMeR, associate researcher, dept. Internal Medicine, Athens, Greece
6. Department of Obstetrics and Gynaecology, University General Hospital of Larisa, Greece


Background: The number of genetic association studies is increasing exponentially. Nonetheless, genetic association reports are prone to potential biases which may influence the reported outcome.

Aim: We hypothesized that positive outcome for a determined polymorphism might be over-reported across genetic association studies analysing a small number of polymorphisms, when compared to studies analysing the same polymorphism together with a high number of other polymorphisms.

Methods: We systematically reviewed published reports on the association of glutathione s-transferase (GST) single-nucleotide polymorphisms (SNPs) and cancer outcome.

Result: We identified 79 eligible trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies analysing one to three polymorphisms (n = 39) were significantly more likely to present positive outcomes, compared to studies examining more than 3 polymorphisms (n=40) p = 0.004; this was particularly evident for studies analysing the GSTM1polymorphism (p =0.001). We found no significant associations between journal impact factor, number of citations, and probability of publishing positive studies or studies with 1-3 polymorphisms examined.

Conclusions: We propose a new subtype of publication bias in genetic association studies. Positive results for genetic association studies analysing a small number of polymorphisms (n = 1-3) should be evaluated extremely cautiously, because a very large number of such studies are inconclusive and statistically under-powered. Indeed, publication of misleading reports may affect harmfully medical decision-making and use of resources, both in clinical and pharmacological development setting.

Keywords: single-nucleotide polymorphisms, genetic association studies, publication-bias, literature bias, translational research.

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How to cite this article:
Valachis A, Mauri D, Neophytou C, Polyzos NP, Tsali L, Garras A, Papanikolau EG. Translational Medicine and Reliability of Single-Nucleotide Polymorphism Studies: Can We Believe in SNP Reports or Not?. Int J Med Sci 2011; 8(6):492-500. doi:10.7150/ijms.8.492. Available from