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BMC Cancer
Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

HFE H63D mutation frequency shows an increase in Turkish women with breast cancer

Authors: Aysen Gunel-Ozcan, Sibel Alyılmaz-Bekmez, Emine Nilufer Guler, Dicle Guc

Published in: BMC Cancer | Issue 1/2006

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Abstract

Background

The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls.

Methods

Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP.

Results

All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176) in the breast cancer patients, and 14% (28/200) in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02).

Conclusion

Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05) computed in this study suggest that H63D has a positive association with breast cancer.
Appendix
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Literature
1.
Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK: A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996, 13: 399-408. 10.1038/ng0896-399.CrossRefPubMed
2.
Beutler L, Beutler E: Hematologically important mutations: iron storage diseases. Blood Cells Mol Dis. 2004, 33: 40-44. 10.1016/j.bcmd.2004.03.002.CrossRefPubMed
3.
Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, Watson N, Tsuchihashi Z, Sigal E, Bjorkman PJ, Schatzman RC: The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc Natl Acad Sci USA. 1998, 95: 1472-1477. 10.1073/pnas.95.4.1472.CrossRefPubMedPubMedCentral
4.
Feder JN, Tsuchihashi Z, Irrinki A, Lee VK, Mapa FA, Morikang E, Prass CE, Starnes SM, Wolff RK, Parkkila S, Sly WS, Schatzman RC: The hemochromatosis founder mutation in HLA-H disrupts b2-microglobulin interaction and cell surface expression. J Biol Chem. 1997, 272: 14025-14028. 10.1074/jbc.272.22.14025.CrossRefPubMed
5.
6.
7.
Waheed A, Parkkila S, Zhou XY, Tomatsu S, Tsuchihashi Z, Feder JN, Schatzman RC, Britton RS, Bacon BR, Sly WS: Hereditary hemochromatosis: effects of C282Y and H63D mutations on association with beta2-microglobulin, intracellular processing, and cell surface expression of the HFE protein in COS-7 cells. Proc Natl Acad Sci USA. 1997, 94: 12384-12389. 10.1073/pnas.94.23.12384.CrossRefPubMedPubMedCentral
8.
Beutler E, Gelbart T, West C, Lee P, Adams M, Blackstone R, Pockros P, Kosty M, Venditti CP, Phatak PD, Seese NK, Chorney KA, Ten Elshof AE, Gerhard GS, Chorney M: Mutation analysis in hereditary hemochromatosis. Blood Cells Mol Dis. 1996, 22: 187-194. 10.1006/bcmd.1996.0027.CrossRefPubMed
9.
Hanson EH, Imperatore G, Burke W: HFE gene and Hereditary Hemochromatosis: a HuGE review. Human Genome Epidemiology. Am J Epidemiol. 2001, 154: 193-206. 10.1093/aje/154.3.193.CrossRefPubMed
10.
Hellerbrand C, Poppl A, Hartmann A, Scholmerich J, Lock G: HFE C282Y heterozygosity in hepatocellular carcinoma: evidence for an increased prevalence. Clin Gastroenterol Hepatol. 2003, 1: 279-284. 10.1016/S1542-3565(03)00132-0.CrossRefPubMed
11.
Cauza E, Peck-Radosavljevic M, Ulrich-Pur H, Datz C, Gschwantler M, Schoniger-Hekele M, Hackl F, Polli C, Rasoul-Rockenschaub S, Muller C, Wrba F, Gangl A, Ferenci P: Mutations of the HFE gene in patients with hepatocellular carcinoma. Am J Gastroenterol. 2003, 98: 442-447. 10.1111/j.1572-0241.2003.07222.x.CrossRefPubMed
12.
Barton JC, Bertoli LF, Acton RT: HFE C282Y and H63D in adults with malignancies in a community medical oncology practice. BMC Cancer. 2004, 4: 6-10.1186/1471-2407-4-6.CrossRefPubMedPubMedCentral
13.
Dorak MT, Burnett AK, Worwood M, Sproul AM, Gibson BE: The C282Y mutation of HFE is another male-specific risk factor for childhood acute lymphoblastic leukemia. Blood. 1999, 94: 3957-3958.PubMed
14.
Dorak MT, Burnett AK, Worwood M: HFE gene mutations in susceptibility to childhood leukemia: HuGE review. Genet Med. 2005, 7: 159-167.CrossRefPubMed
15.
Beckman LE, Van Landeghem GF, Sikström C, Wahlin A, Markevarn B, Hallmans G, Lenner P, Athlin L, Stenling R, Beckman L: Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders. Carcinogenesis. 1999, 20: 1231-1233. 10.1093/carcin/20.7.1231.CrossRefPubMed
16.
Altes A, Gimferrer E, Capella G, Barcelo MJ, Baiget M: Colorectal cancer and HFE gene mutations. Haematologica. 1999, 84: 479-480.PubMed
17.
Robinson JP, Johnson VL, Rogers PA, Houlston RS, Maher ER, Bishop DT, Evans DG, Thomas HJ, Tomlinson IP, Silver AR: Evidence for association between compound heterozygosity for germ line mutations in the hemochromatosis (HFE) gene and increased risk colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1460-1463. 10.1158/1055-9965.EPI-04-0672.CrossRefPubMed
18.
Kallianpur AR, Hall LD, Yadav M, Christman BW, Dittus RS, Haines JL, Parl FF, Summar ML: Increased Prevalence of the HFE C282Y Hemochromatosis Allele in Women with Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2004, 13: 205-212. 10.1158/1055-9965.EPI-03-0188.CrossRefPubMed
19.
Hannuksela J, Savolainen ER, Koistinen P, Parkkila S: Prevalence of HFE genotypes, C282Y and H63D, in patients with hematologic disorders. Haematologica. 2002, 87: 131-135.PubMed
20.
van der ADL, van der Hel O, Roest M, van der Shouw YT, van Gils CH, Marx JJ, van Noord PA, Peeters PH: Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands). Cancer Causes Control. 2003, 14: 541-545. 10.1023/A:1024839528684.CrossRef
21.
Dorak MT, Burnett AK, Worwood M: Hemochromatosis gene in leukemia and lymphoma. Leuk Lymphoma. 2002, 43: 467-477. 10.1080/10428190290011930.CrossRefPubMed
22.
Abraham BK, Justenhoven C, Pesch B, Harth V, Weirich G, Baisch C, Rabstein S, Ko YD, Bruning T, Fischer HP, Haas S, Brod S, Oberkanins C, Hamann U, Brauch H, GENICA Network: Investigation of genetic variants of genes of the hemochromatosis pathway and their role in breast cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14: 1102-1107. 10.1158/1055-9965.EPI-05-0013.CrossRefPubMed
23.
Nunoshiba T, Obata F, Boss AC, Oikawa S, Mori T, Kawanishi S, Yamamoto K: Role of iron and superoxide for generation of hydroxyl radical, oxidative DNA lesions, and mutagenesis in Escherichia coli. J Biol Chem. 1999, 274: 34832-34837. 10.1074/jbc.274.49.34832.CrossRefPubMed
24.
Sarkar B: Metal replacement in DNA-binding zinc finger proteins and its relevance to mutagenicity and carcinogenicity through free radical generation. Nutrition. 1995, 11: 646-649.PubMed
25.
26.
Green R, Esparza I, Schreiber R: Iron inhibits the non-specific tumoricidal activity of macrophages: a possible contributory mechanism for neoplasia in hemochromatosis. Ann N Y Acad Sci. 1988, 526: 301-309.CrossRefPubMed
27.
Bergeron RJ, Streiff RR, Elliot GT: Influence of iron on in vivo proliferation and lethality of L 1210 cells. J Nutr. 1985, 115: 369-374.PubMed
28.
Koeken A, Cobbaert C, Quint W, van Doorn LJ: Genotyping of hemochromatosis-associated mutations in the HFE gene by PCR-RFLP and a novel reverse hybridization method. Clin Chem Lab Med. 2002, 40 (2): 122-125. 10.1515/CCLM.2002.021.CrossRefPubMed
29.
30.
Bozkaya H, Bektas M, Metin O, Erkan O, Ibrahimoglu D, Dalva K, Akbiyik F, Gurel S, Bozdayi AM, Akay C, Yurdaydin C, Aslan O, Uzunalimoglu O: Screening for hemochromatosis in Turkey. Dig Dis Sci. 2004, 49: 444-449. 10.1023/B:DDAS.0000020500.26184.ce.CrossRefPubMed
31.
Simsek H, Sumer H, Yilmaz E, Balaban YH, Ozcebe O, Hascelik G, Buyukask Y, Tatar G: Frequency of HFE mutations among Turkish blood donors according to transferrin saturation: genotype screening for hereditary hemochromatosis among voluntary blood donors in Turkey. J Clin Gastroenterol. 2004, 38: 671-675. 10.1097/01.mcg.0000135901.52818.f7.CrossRefPubMed
32.
33.
Malins DC, Polissar NL, Gunselman SJ: Progression of human breast cancer to the metastatic state is linked to hydroxyl radical-induced DNA damage. Proc Natl Acad Sci USA. 1996, 93: 2557-2563. 10.1073/pnas.93.6.2557.CrossRefPubMedPubMedCentral
34.
Kondrashova TV, Neriishi K, Ban S, Ivanova TI, Krikunova LI, Shentereva NI, Smirnova IA, Zharikova IA, Konova MV, Taira S, Tsyb AF: Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers. Biochim Biophys Acta. 2005, 1762 (1): 59-65.CrossRefPubMed
35.
Syrjakoski KFH, Ikonen T, Kuukasjarvi T, Autio V, Matikainen MP, Tammela TLJ, Koivisto PA, Schleutker J: Hemochromatosis gene mutations among Finnish male breast and prostate cancer patients. Int J Cancer. 2006, 118: 518-520. 10.1002/ijc.21331.CrossRefPubMed
36.
Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P: Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005, 352: 1769-1778. 10.1056/NEJMoa041534.CrossRefPubMed
37.
Martinez di Montemuros F, Tavazzi D, Salsano E, Piepoli T, Pollo B, Fiorelli G, Finocchiaro G: High frequency of the H63D mutation of the hemochromatosis gene (HFE) in malignant gliomas. Neurology. 2001, 57: 1342-CrossRefPubMed
38.
Tomatsu S, Orii KO, Fleming RE, Holden CC, Waheed A, Britton RS, Gutierrez MA, Velez-Castrillon S, Bacon BR, Sly WS: Contribution of the H63D mutation in HFE to murine hereditary hemochromatosis. Proc Natl Acad Sci USA. 2003, 100: 15788-15793. 10.1073/pnas.2237037100.CrossRefPubMedPubMedCentral
39.
Whitfield JB, Cullen LM, Jazwinska EC, Powell LW, Heath AC, Zhu G, Duffy DL, Martin NG: Effects of HFE C282Y and H63D polymorphisms and polygenic background on iron stores in a large community sample of twins. Am J Hum Genet. 2000, 66: 1246-1258. 10.1086/302862.CrossRefPubMedPubMedCentral
40.
Beutler E, Felitti VJ, Koziol JA, Ho NJ, Gelbart T: Penetrance of 845G--> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002, 359: 211-218. 10.1016/S0140-6736(02)07447-0.CrossRefPubMed
41.
Jackson H, Carter K, Darke C, Guttridge MG, Ravine D, Hutton RD, Napier JA, Worwood M: HFE mutations, iron deficiency and overload in 10,500 blood donors. Br J Haematol. 2001, 114: 474-484. 10.1046/j.1365-2141.2001.02949.x.CrossRefPubMed
42.
Burke W, Imperatore G, McDonnell SM, Baron RC, Khoury MJ: Contribution of different HFE genotypes to iron overload disease: a pooled analysis. Genet Med. 2000, 2: 271-277.CrossRefPubMed
43.
Porto G, Alves H, Rodrigues P, Cabeda JM, Portal C, Ruivo A, Justica B, Wolff R, de Sousa M: Major histocompatibility complex class I associations in iron overload: evidence for a new link between the HFE H63D mutation, HLA-A29, and non-classical forms of hemochromatosis. Immunogenetics. 1998, 47: 404-410. 10.1007/s002510050376.CrossRefPubMed
44.
Cardoso CS, Alves H, Mascarenhas M, Goncalves R, Oliveira P, Rodrigues P, Cruz E, de Sousa M, Porto G: Co-selection of the H63D mutation and the HLA-29 allele: a new paradigm of linkage disequilibrium?. Immunogenetics. 2002, 53: 1002-1008. 10.1007/s00251-001-0414-8.CrossRefPubMed
45.
de Jong M, Nolte IM, de Vries EGE, Schaapveld M, Kleibeuker JH, Oosterom E, Oosterwijk JC, van der Hout AH, van der Steege G, Bruinenberg M, Boezen HM, Te Meerman GJ, van der Graaf WT: The HLA class III subregion is responsible for an increased breast cancer risk. Hum Mol Gen. 2003, 12: 2311-2319. 10.1093/hmg/ddg245.CrossRefPubMed
46.
Cruz E, Vieira J, Gonçalves R, Alves H, Almeida S, Rodrigues P, Lacerda R, Porto G: Involvement of the Major Histocompatibility Complex region in the genetic regulation of circulating CD8+ T-cell numbers in humans. Tissue Antigens. 2004, 64: 25-34. 10.1111/j.1399-0039.2004.00245.x.CrossRefPubMed
Metadata
Title
HFE H63D mutation frequency shows an increase in Turkish women with breast cancer
Authors
Aysen Gunel-Ozcan
Sibel Alyılmaz-Bekmez
Emine Nilufer Guler
Dicle Guc
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-37

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