Journal of Experimental & Clinical Cancer Research 2009, 28:115 http://www.jeccr.com/content/28/1/115 Previously, a number of studies indicate that family his- tory is a risk factor for breast cancer [5], indicating the pos- sible roles for genetic variations on the increased susceptibility to breast cancer. Recent published meta- analyses suggest that polymorphisms of Fok1 [6], XRCC1 codon 399[7] and methylenetetrahydrofolate reduct- ase[8] might have a significant association with increased breast cancer risk. Nevertheless, conversely, some meta- analysis failed to suggest a marked association of increased susceptibility to breast cancer with polymor- phisms of some genes, such as Estrogen receptor alpha [9], CYP1A1 [10] and base-excision repair pathway genes [11]. Recently, a growing body of research has conducted on the association of breast cancer risk with tumour suppres- sors. TP53, one of the most extensive studied genes as a tumor suppressor, has been thought to have a critical function in cell cycle regulation. In case of its mutation, this regulation could be lost, resulting in cell proliferation without control and development of cancer. Previously, TP53 mutation has been indicated to associate with risks of a number of cancers such as lung cancer[12], breast cancer [13] and colorectal cancer [14]. The loss of TP53 gene could damage its DNA-binding properties and tran- scription factor function, thus leading to aberrant cell pro- liferation. In human populations, the TP53 gene is polymorphic at amino acid 72 of the protein that it encodes. Recently, much attention has been focused on possible associations of TP53 polymorphisms and cancer risks. The most informative polymorphism in TP53 gene is located in exon 4 at codon 72, which encodes two distinct func- tional allelic forms arginine (Arg) and proline (Pro) because of a transversion G to C [15], resulting in different biochemical and biological protein features. Conse- quently, three distinct genotypes were created, namely, homozygous for arginine (Arg/Arg), homozygous for pro- line (Pro/Pro), and heterozygous (Arg/Pro). Previously, Arg variant has been thought to increase susceptibility to gastric cancer[16] and Arg homozygosity might contribute to cervical cancer [17]. Nevertheless, Pro homozygosity might have an association with lung [18] and hepotocel- lular cancer [19] risk. The heterozygous genotype Arg/Pro has been implicated as a risk factor for bladder cancer [20]. In recent literature, inconclusive data regarding TP53 codon 72 were found in some cancers, such as gastric can- cer in which controversial conclusions were obtained in Asians [21] and in individuals from Northern Brazil [22]. Similarly, up to date, published data on the possible asso- ciation of TP53 codon 72 polymorphism with breast car- cinoma have also generated controversial and inconclusive results. To the best of our knowledge, whether TP53 codon 72 polymorphism could increase breast cancer risk remains largely uncertain. To clarify this association may help us better understand the possible risk of breast cancer and therefore contribute to its preven- tion. As a single study may have been underpowered in clarify- ing the relationship of TP53 codon 72 polymorphisms with breast carcinoma susceptibility, in the present study we performed evidence-based quantitative meta-analyses that can increase statistical power to address the associa- tion. Materials and methods Literature search strategy for identification of the studies We carried out a search in the Medline, EMBASE, OVID, Sciencedirect, and Chinese National Knowledge Infra- structure (CNKI) without a language limitation, covering all papers published up to Jan 2009, with a combination of the following keywords: TP53, P53, codon 72, breast, carcinoma, neoplasm, tumor, cancer and polymorphism. The keywords were paired each time in order to get more rele- vant information. For example, the word "breast" was always kept and others were substituted in different moments. We evaluated potentially associated publications by checking their titles and abstracts and then procured the most relevant publications for a closer examination. Moreover, the reference lists of the selected papers were also screened for other potential articles that possibly have been missed in the initial search. The following cri- teria were used for the literature selection for the further meta-analysis: 1. Studies concerning the association of TP53 codon 72 polymorphism with breast carcinoma; 2. Case–control or cohort studies; 3. Papers presenting the breast cancer diagnoses and the sources of cases and controls; 4. Articles offering the size of the sample, odds ratios (ORs) and their 95% confidence intervals (CIs) or the information that can help infer the results; 5. The number of individuals homozygous for arginine (Arg/Arg), proline (Pro/Pro) and heterozygous (Pro/Arg) in breast cancer cases and controls should be offered; Page 2 of 9 (page number not for citation purposes)