Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders
A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type...
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| Veröffentlicht in: | Carcinogenesis (New York) 1999-07, Vol.20 (7), p.1231-1233 |
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| creator | Beckman, L.E. Van Landeghem, G.F. Sikström, C. Wahlin, A. Markevärn, B. Hallmans, G. Lenner, P. Athlin, L. Stenling, R. Beckman, L. |
| description | A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0–3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0–59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders. |
| doi_str_mv | 10.1093/carcin/20.7.1231 |
| format | Article |
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In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0–3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0–59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.</description><identifier>ISSN: 0143-3334</identifier><identifier>ISSN: 1460-2180</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/20.7.1231</identifier><identifier>PMID: 10383894</identifier><identifier>CODEN: CRNGDP</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>Alleles ; Biological and medical sciences ; Breast Neoplasms - genetics ; Colorectal Neoplasms - genetics ; Female ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Gynecology. Andrology. Obstetrics ; haemochromatosis gene ; Hemochromatosis - genetics ; Hemochromatosis Protein ; hereditary haemochromatosis ; Heterozygote ; HFE ; Histocompatibility Antigens Class I - genetics ; HLA Antigens - genetics ; Humans ; Male ; Mammary gland diseases ; Medical sciences ; Membrane Proteins ; Multiple Myeloma - genetics ; Mutation ; Odds Ratio ; Receptors, Transferrin - genetics ; Risk Assessment ; Stomach. Duodenum. Small intestine. Colon. Rectum. 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In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0–3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0–59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.</description><subject>Alleles</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Female</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Frequency</subject><subject>Genetic Predisposition to Disease</subject><subject>Genotype</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>haemochromatosis gene</subject><subject>Hemochromatosis - genetics</subject><subject>Hemochromatosis Protein</subject><subject>hereditary haemochromatosis</subject><subject>Heterozygote</subject><subject>HFE</subject><subject>Histocompatibility Antigens Class I - genetics</subject><subject>HLA Antigens - genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Membrane Proteins</subject><subject>Multiple Myeloma - genetics</subject><subject>Mutation</subject><subject>Odds Ratio</subject><subject>Receptors, Transferrin - genetics</subject><subject>Risk Assessment</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>TFR</subject><subject>transferrin receptor</subject><subject>transferrin receptor gene</subject><subject>Tumors</subject><subject>wild-type</subject><issn>0143-3334</issn><issn>1460-2180</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE2LFDEQhoMo7uzo3ZM04rVnU0k66RxlUXdxV8EPEC8hna64WWeSMcng-u_N0oN6Kqj3eavgIeQZ0A1Qzc-czS7EM0Y3agOMwwOyAiFpz2CkD8mKguA951yckNNSbikFyQf9mJwA5SMftVgRvIwVs3U1pNhNWH8hxu7G4i65m5x2tqYSSmfj3NVsY_GYc4hdRof7mnL3HSOWrm3m4FuGsXYR035rSw2uLUvKM-byhDzydlvw6XGuyZc3rz-fX_RXH95enr-66p3gUHvhBzZbKqmUyguccIRp9H722mqBLWSTHJBZASNYNjqlqHaoEQcJwJXia_JiubvP6ecBSzW36ZBje2kYaC5Ay6FBdIFcTqVk9Gafw87m3waouddqFq2GUaPMvdZWeX68e5h2OP9XWDw24OURsMXZrW-uXCj_uHFguslfk37BQql49ze2-YeRiqvBXHz9ZvT1u0_s_bU0H_kfE3mSmA</recordid><startdate>19990701</startdate><enddate>19990701</enddate><creator>Beckman, L.E.</creator><creator>Van Landeghem, G.F.</creator><creator>Sikström, C.</creator><creator>Wahlin, A.</creator><creator>Markevärn, B.</creator><creator>Hallmans, G.</creator><creator>Lenner, P.</creator><creator>Athlin, L.</creator><creator>Stenling, R.</creator><creator>Beckman, L.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>19990701</creationdate><title>Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders</title><author>Beckman, L.E. ; Van Landeghem, G.F. ; Sikström, C. ; Wahlin, A. ; Markevärn, B. ; Hallmans, G. ; Lenner, P. ; Athlin, L. ; Stenling, R. ; Beckman, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-4f52da060667f4ebe81b8ffdf9a94ef522b65e2a4181a28c7709ce9ee56113773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Alleles</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Female</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease</topic><topic>Genotype</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>haemochromatosis gene</topic><topic>Hemochromatosis - genetics</topic><topic>Hemochromatosis Protein</topic><topic>hereditary haemochromatosis</topic><topic>Heterozygote</topic><topic>HFE</topic><topic>Histocompatibility Antigens Class I - genetics</topic><topic>HLA Antigens - genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Membrane Proteins</topic><topic>Multiple Myeloma - genetics</topic><topic>Mutation</topic><topic>Odds Ratio</topic><topic>Receptors, Transferrin - genetics</topic><topic>Risk Assessment</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>TFR</topic><topic>transferrin receptor</topic><topic>transferrin receptor gene</topic><topic>Tumors</topic><topic>wild-type</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beckman, L.E.</creatorcontrib><creatorcontrib>Van Landeghem, G.F.</creatorcontrib><creatorcontrib>Sikström, C.</creatorcontrib><creatorcontrib>Wahlin, A.</creatorcontrib><creatorcontrib>Markevärn, B.</creatorcontrib><creatorcontrib>Hallmans, G.</creatorcontrib><creatorcontrib>Lenner, P.</creatorcontrib><creatorcontrib>Athlin, L.</creatorcontrib><creatorcontrib>Stenling, R.</creatorcontrib><creatorcontrib>Beckman, L.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beckman, L.E.</au><au>Van Landeghem, G.F.</au><au>Sikström, C.</au><au>Wahlin, A.</au><au>Markevärn, B.</au><au>Hallmans, G.</au><au>Lenner, P.</au><au>Athlin, L.</au><au>Stenling, R.</au><au>Beckman, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>1999-07-01</date><risdate>1999</risdate><volume>20</volume><issue>7</issue><spage>1231</spage><epage>1233</epage><pages>1231-1233</pages><issn>0143-3334</issn><issn>1460-2180</issn><eissn>1460-2180</eissn><coden>CRNGDP</coden><abstract>A number of genes are involved in iron metabolism, including the transferrin receptor (TFR) and haemochromatosis (HFE) genes. In previous investigations an increased risk for neoplastic disease has been observed in individuals homo- and heterozygous for hereditary haemochromatosis. The HFE wild-type gene product complexes with the transferrin receptor (TF) and two different HFE mutations (Cys282Tyr and His63Asp) have been found to increase the affinity of TFR for TF and increase cellular iron uptake. In a recent study we found no associations for HFE and TFR separately, but an interaction between HFE and TFR genotypes in multiple myeloma. Individuals carrying the HFE Tyr282 allele (homo- and heterozygotes) in combination with homozygosity for the TFR Ser142 allele had an increased risk. In the present study the same association was found in breast and colorectal cancer. The odds ratio for all three neoplasms combined was 2.0 (95% CI 1.0–3.8). The risk for neoplastic disease was further increased (OR 7.7, 95% CI = 1.0–59.9) when the analysis was restricted to HFE Tyr homozygotes and compound heterozygotes in combination with TFR Ser homozygosity. Thus, an interaction between HFE and TFR alleles may increase the risk for different neoplastic disorders.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>10383894</pmid><doi>10.1093/carcin/20.7.1231</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Alleles Biological and medical sciences Breast Neoplasms - genetics Colorectal Neoplasms - genetics Female Gastroenterology. Liver. Pancreas. Abdomen Gene Frequency Genetic Predisposition to Disease Genotype Gynecology. Andrology. Obstetrics haemochromatosis gene Hemochromatosis - genetics Hemochromatosis Protein hereditary haemochromatosis Heterozygote HFE Histocompatibility Antigens Class I - genetics HLA Antigens - genetics Humans Male Mammary gland diseases Medical sciences Membrane Proteins Multiple Myeloma - genetics Mutation Odds Ratio Receptors, Transferrin - genetics Risk Assessment Stomach. Duodenum. Small intestine. Colon. Rectum. Anus TFR transferrin receptor transferrin receptor gene Tumors wild-type |
| title | Interaction between haemochromatosis and transferrin receptor genes in different neoplastic disorders |
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