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Molecular Diagnosis & Therapy
Published in: Molecular Diagnosis & Therapy 1/2014

Open Access 01-02-2014 | Original Research Article

An Analysis of Polymorphisms Within the Wnt Signaling Pathway in Relation to Ovarian Cancer Risk in a Polish Population

Authors: Adrianna Mostowska, Piotr Pawlik, Stefan Sajdak, Janina Markowska, Monika Pawałowska, Margarita Lianeri, Paweł P. Jagodzinski

Published in: Molecular Diagnosis & Therapy | Issue 1/2014

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Abstract

Background and Objective

The Wnt/β-catenin signaling pathway has been considered to be a factor in the development and progression of ovarian cancer.

Methods

All patients with ovarian cancer and controls were tested for BRCA1 mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers were excluded from the association analysis. We studied nine single nucleotide polymorphisms (SNPs) located in CTNNB1 (β-catenin) [rs4533622, rs2953], APC (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087, rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations (n = 228) and controls (n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771, AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the appropriate restriction enzyme digestion [PCR–restriction fragment length polymorphism (PCR-RFLP)].

Results

The most common BRCA1/BRCA2 mutations were identified in 30 patients with ovarian cancer. These mutations were not found in controls. The lowest p values of the trend test (p trend) were observed for the APC rs351771 and rs11954856 SNPs in patients with ovarian cancer (p trend = 0.006 and p trend = 0.007, respectively). Using a dominant inheritance model, we found that the APC rs11954856 SNP is associated with an increased risk of ovarian cancer development [odds ratio = 2.034 (95 % CI 1.302–3.178); p = 0.002]. We also observed significant allelic differences for the APC rs351771 SNP between patients and controls (p = 0.006).

Conclusion

Our study demonstrated significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish women with ovarian cancer.
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Literature
1.
Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007;18(3):581–92.PubMedCrossRef
2.
3.
Sueblinvong T, Carney ME. Current understanding of risk factors for ovarian cancer. Curr Treat Options Oncol. 2009;10(1–2):67–81.PubMedCrossRef
4.
Berchuck A, Schildkraut JM, Marks JR, et al. Managing hereditary ovarian cancer risk. Cancer. 1999;86(11 Suppl):2517–24.PubMedCrossRef
5.
Frank TS, Manley SA, Olopade OI, et al. Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol. 1998;16(7):2417–25.PubMed
6.
Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol. 2000;19(1):3–10.PubMedCrossRef
7.
Choi YP, Shim HS, Gao MQ, et al. Molecular portraits of intratumoral heterogeneity in human ovarian cancer. Cancer Lett. 2011;307(1):62–71.PubMedCrossRef
8.
Bitler BG, Nicodemus JP, Li H, et al. Wnt5a suppresses epithelial ovarian cancer by promoting cellular senescence R. Cancer Res. 2011;71(19):6184–94.PubMedCentralPubMedCrossRef
9.
10.
Hsieh M, Johnson MA, Greenberg NM, et al. Regulated expression of Wnts and Frizzleds at specific stages of follicular development in the rodent ovary. Endocrinology. 2002;143(3):898–908.PubMed
11.
Vainio S, Heikkila M, Kispert A, et al. Female development in mammals is regulated by Wnt-4 signalling. Nature. 1999;397(6718):405–9.PubMedCrossRef
12.
Novak A, Dedhar S. Signaling through beta-catenin and Lef/Tcf. Cell Mol Life Sci. 1999;56(5–6):523–37.PubMedCrossRef
13.
Herr P, Hausmann G, Basler K. WNT secretion and signalling in human disease. Trends Mol Med. 2012;18(8):483–93.PubMedCrossRef
14.
15.
Sagae S, Kobayashi K, Nishioka Y, et al. Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: frequent mutations in endometrioid carcinomas. Jpn J Cancer Res. 1999;90(5):510–5.PubMedCrossRef
16.
Saegusa M, Okayasu I. Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation. J Pathol. 2001;194(1):59–67.PubMedCrossRef
17.
Wu R, Zhai Y, Fearon ER, et al. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res. 2001;61(22):8247–55.PubMed
18.
Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4:a008052.
19.
Wang S, Tian Y, Wu D, et al. Genetic variation of CTNNB1 gene is associated with susceptibility and prognosis of gastric cancer in a Chinese population. Mutagenesis. 2012;27(6):623–30.PubMedCrossRef
20.
Starker LF, Fonseca A, Akerström G, et al. Evidence of a stabilizing mutation of β-catenin encoded by CTNNB1 exon 3 in a large series of sporadic parathyroid adenomas. Endocrine. 2012;42(3):612–5.PubMedCrossRef
21.
Yoshie T, Nishiumi S, Izumi Y, et al. Regulation of the metabolite profile by an APC gene mutation in colorectal cancer. Cancer Sci. 2012;103(6):1010–21.PubMedCrossRef
22.
Erbilgin Y, Ng OH, Mavi N, et al. Genetic alterations in members of the Wnt pathway in acute leukemia. Leuk Lymphoma. 2012;53(3):508–10.PubMedCrossRef
23.
Sercan Z, Pehlivan M, Gokturk D, et al. Beta-catenin mutations are not observed in chronic myeloid leukemia. Tumori. 2009;95(6):836–9.PubMed
24.
Wang X, Goode EL, Fredericksen ZS, et al. Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2101–8.PubMedCentralPubMedCrossRef
25.
Laken SJ, Peterson GM, Gruber SB, et al. Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC. Nat Genet. 1997;17(1):79–83.PubMedCrossRef
26.
Pinarbasi E, Gunes EG, Pinarbasi H, et al. AXIN2 polymorphism and its association with prostate cancer in a Turkish population. Med Oncol. 2011;28(4):1373–8.
27.
Gunes EG, Pinarbasi E, Pinarbasi H, et al. Strong association between lung cancer and the AXIN2 polymorphism. Mol Med Report. 2009;2(6):1029–35.
28.
Gunes EG, Pinarbasi E, Pinarbasi H. AXIN2 polymorphism and its association with astrocytoma in a Turkish population. Mol Med Report. 2010;3(4):705–9.
29.
Kanzaki H, Ouchida M, Hanafusa H, et al. Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. Int J Mol Med. 2006;18(2):279–84.PubMed
30.
Wong HL, Peters U, Hayes RB, et al. Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk. Eur J Cancer. 2010;46(13):2457–66.PubMedCentralPubMedCrossRef
31.
Guerreiro CS, Cravo ML, Brito M, et al. The D1822V APC polymorphism interacts with fat, calcium, and fiber intakes in modulating the risk of colorectal cancer in Portuguese persons. Am J Clin Nutr. 2007;85(6):1592–7.PubMed
32.
Wu R, Hendrix-Lucas N, Kuick R, et al. Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/beta-catenin and PI3K/Pten signaling pathways. Cancer Cell. 2007;11(4):321–33.PubMedCrossRef
33.
34.
Dudbridge F. Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered. 2008;66(2):87–98.PubMedCentralPubMedCrossRef
35.
Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics. 2003;19(3):376–82.PubMedCrossRef
36.
Abrahamson J, Moslehi R, Vesprini D, et al. No association of the I1307K APC allele with ovarian cancer risk in Ashkenazi Jews. Cancer Res. 1998;58(14):2919–22.PubMed
37.
Gershoni-Baruch R, Patael Y, Dagan, et al. Association of the I1307K APC mutation with hereditary and sporadic breast/ovarian cancer: more questions than answers. Br J Cancer. 2000;83(2):153–5.PubMedCentralPubMedCrossRef
38.
Wright K, Wilson P, Morland S, et al. Beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours. Int J Cancer. 1999;82(5):625–9.PubMedCrossRef
39.
Sarrió D, Moreno-Bueno G, Sánchez-Estévez C, et al. High frequency of beta-catenin mutations in borderline endometrioid tumours of the ovary. Expression of cadherins and catenins correlates with distinct histologic types of ovarian carcinomas. Hum Pathol. 2006;37(5):1042–9.PubMedCrossRef
40.
Eklof Spink K, Fridman SG, Weis WI. Molecular mechanisms of beta-catenin recognition by adenomatous polyposis coli revealed by the structure of an APC-beta-catenin complex. EMBO J. 2001;20(22):6203–12.PubMedCrossRef
41.
Nakamura T, Hamada F, Ishidate T, et al. Axin, an inhibitor of the Wnt signalling pathway, interacts with beta-catenin, GSK-3 beta and APC and reduces the beta-catenin level. Genes Cells. 1998;3(6):395–403.PubMedCrossRef
42.
Notaridou M, Quaye L, Dafou D, et al. Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer. Int J Cancer. 2011;128(9):2063–74.PubMedCentralPubMedCrossRef
43.
Song H, Ramus SJ, Tyrer J, et al. A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet. 2009;41(9):996–1000.PubMedCentralPubMedCrossRef
44.
Goode EL, Chenevix-Trench G, Song H, et al. A genome-wide association study identifies susceptibility loci for ovarian cancer at 2q31 and 8q24. Nat Genet. 2010;42(10):874–9.PubMedCentralPubMedCrossRef
45.
Metadata
Title
An Analysis of Polymorphisms Within the Wnt Signaling Pathway in Relation to Ovarian Cancer Risk in a Polish Population
Authors
Adrianna Mostowska
Piotr Pawlik
Stefan Sajdak
Janina Markowska
Monika Pawałowska
Margarita Lianeri
Paweł P. Jagodzinski
Publication date
01-02-2014
Publisher
Springer International Publishing
Published in
Molecular Diagnosis & Therapy / Issue 1/2014
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI
https://doi.org/10.1007/s40291-013-0059-y

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