role of the p53 protein in regulation of cell cycle , cell growth and maintenance of genomic stability has been largely described . numerous alterations in p53 lead to neoplasmatic transformation . a rare familial li - fraumeni syndrome was associated with germline mutations in this gene . in families with li - fraumeni syndrome most commonly observed neoplasms are : soft tissue sarcomas , osteosarcomas , brain tumors , breast cancer , leukemias , and adrenocortical tumors , but not ovarian cancer   however , over 200 epidemiologic studies evaluated ovarian cancer risk associated with snp variants in tp53 . among them the tp53 215 g > c ( rs1042522 , p.pro72arg ) is one of the most commonly disputed . the results differ between populations with little or no evidence for the risk of cancer for opposite pro or arg alleles [ 28 ] . similar thus inconclusive results are observed in ovarian cancer [ 911 ] and thereby reproduce previous findings . these equivocal data may suggest that the tp53 rs1042522 does not influence carcinogensis directly , but might be linked to another pathogenic alteration responsible for higher risk of ovarian cancer . one of the candidate gene is the wrap53 ( also denoted as wdr79 and tcab1 ) located on chromosome 17p13 which partly overlaps the tp53 and interacts with the 5utr of p53 . wrap53 is required for control and induction of p53 upon dna damage to maintain normal levels of p53 in the cell preventing its deprivation which may then lead to a cancer   the identification of wrap53 as a regulator of p53 shows that dysfunction of wrap53 itself may be a separate cause leading to a cancer [ 13 , 14]recent reports suggested that common variations in wrap53 may independently increase risk of estrogen receptor negative breast cancers   and correlates with poor prognosis of head and neck cancer . aim of this study was the analysis of association between snps located in wrap53tp53 region : rs1042522 , rs2287497 , rs2287498 and ovarian cancer risk in the polish population . the studied group consisted of 626 ovarian cancer patients from the registry of international hereditary cancer centre in szczecin , poland , who were diagnosed in years 20032009 in cooperating oncology centers in szczecin and pozna . the control population consisted of 1045 healthy women who visited their family doctors in the area of szczecin . mean age and age structure did not differ significantly between cases and controls ( age range 2679 vs 2779 , mean age 55.5 vs 56 respectively ) . the study protocol was approved by the institutional review board of the pomeranian medical university , the approval was obtained from all cooperating institutions , and signed informed consent for genetic testing was obtained from all participants . 10  ml of peripheral blood samples for dna extraction were acquired from cases and controls . all samples were genotyped with use of simple probes on roche lightcycler 480 in 384 well plates in 10 l pcr reaction using 1:10 dilution of lightcycler 480 genotyping master , 0.5  m of excess primer , 0.05  m of limiting primer , 0.6  m of probe and ~20  ng of dna according to roche applied sciences genotyping master mix instructions . all statistical calculations were performed using the common homozygous of each snp as the reference value . each of the snps was evaluated individually per genotype by calculating odds ratio ( or ) , 95  % confidence interval ( 95  % ci ) , p values using a chi test . genotype distributions of all three examined snps in control population were in accordance with hardy  weinberg equilibrium : rs1042522 ( maf  =  0.28 , hwe  =  0.19 ) ; rs2287497 ( maf  =  0.12 , hwe  =  0.65 ) , rs2287498 ( maf  =  0.10 , hwe  =  0.57 ) . the distribution of the genotypes among ovarian cancer samples revealed an association of studied snps with ovarian cancer risk . rs1042522 cc homozygotes were more frequent in cases when compared to controls ( or  =  1.46 ) ( table  1 ) . similar association was observed for wrap53 rs2287497 and rs2287498 where tt homozygotes and aa homozygotes , were more frequent among cases than controls ( or  =  1.95 , 2.65 , respectively ) ( table  1 ) . all the results were statistically significant.table  1distribution of genotypes among ovarian cancerssitecasescontrolsorpci 95  % n(%)n(%)rs10425225cc599.4726.91.460.031.002.11cg26542.343641.71.080.250.881.33gg30248.253751.41.001.00rs2287497tt203.2171.61.950.031.013.76tg11818.922021.10.890.190.721.18cc48878.080877.31.001.00rs2287498aa193.0121.22.650.011.275.50ga9915.818417.60.900.240.691.18gg50881.284981.21.001.00 distribution of genotypes among ovarian cancers a combined analysis of examined three snps showed an even stronger association with ovarian cancer risk for cases with three rare homozygotes cc  +  tt  +  aa versus wild type homozygotes gg  +  cc  +  gg ( or  =  4.76 p  =  0.0006 ci 95  % 1.84-12.32 ) . however , detailed studies around this region will be needed to clarify the observed association of that specific homozygosity in other populations . the ambiguous associations found for rs1042522 with little or no evidence for the risk of ovarian cancer were previously described in different populations , similarly neither tp53 germline mutations nor li - fraumeni syndrome was proven to be associated with an increased risk of ovarian cancer . hence the hypothesis that an evaluation of snps located in close proximity to tp53 may reveal that rs1042522 is just a marker of other pathogenic alleles . wrap53 is one of the candidate flanking genes to tp53 located on antisense strand to tp53 . an analysis of the literature revealed studies involving genotyping of 23 snps in the tp53 region including some variants outside the tp53 coding sequence , among them snps located in fact within wrap53 . previously published multicenter pooled data suggested an association between rs2287497 and rs2287498 with serous invasive ovarian cancers , but the results were inconsistent between analyzed populations [ 10 , 11 ] . rs2287498 is a synonymous amino acid change in exon 2 ( f150f ) of wrap53 gene , expected to affect function at a splice site , rs2287497 is an intronic change , however supportive of an association . the study of schildkraut included a small number of polish ovarian cancer patients , however narrowed to serous ovarian cancer cases only , because of the a priori belief that tp53 variants might be more closely related to serous cancers . schildkraut findings showed a trend consistent with our results , but due to relatively smaller groups ( 118 ovarian cancers vs. 618 controls ) the scores were not statistically significant leaving the case open . our results provide the evidence for an association between snps both in tp53 and wrap53 and a risk of invasive ovarian cancer in poland . our results might be a suggestive evidence that specific homozygosity of several snps in tp53wrap53 region is significantly overrepresented in ovarian cancer patients . the observations suggest a stronger association of both rs2287497 and rs2287498 ( wrap53 variants ) than of rs1042522 ( tp53 variant ) and lead to a conclusion that snps in wrap53 is more strongly associated with an ovarian cancer risk than rs1042522 in tp53 . it is possible that other variants of wrap53 , not selected for the evaluation , are also related to the disease .