Skip to main content
Top
Published in: Tumor Biology 9/2015

01-09-2015 | Research Article

Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps

Authors: Agustin Castiella, Fernando Múgica, Eva Zapata, Leire Zubiaurre, Arantxa Iribarren, MªDolores de Juan, Luis Alzate, Ines Gil, Gregorio Urdapilleta, Pedro Otazua, José Ignacio Emparanza

Published in: Tumor Biology | Issue 9/2015

Login to get access

Abstract

A cohort study of patients included in the Basque Country colorectal cancer (CRC) screening programme was carried out to assess the risk of adenomatous polyps and CRC (P-CRC) associated with HFE gene mutations, with gender and with iron biomarkers (serum ferritin (SF), iron (Fe) and transferrin saturation index (TSI)). Among 432 included patients (mean age 59.8 years), 263 were men (60.9 %) and 169 women (39.1 %). P-CRC were identified in 221 patients (51.2 %) and no polyps (NP) in 211 patients (48.8 %). HFE mutations were identified in 43.8 % of the patients. C282Y/wt genotypic frequency was 6.8 % in the P-CRC group and 1.4 % in the NP group (p < 0.05). The allelic frequency was 3.8 versus 1.2 % (p < 0.05). For laboratory, all three iron biomarkers showed a statistically significant difference: mean Fe, 91.29 ± 34 for P-CRC and 80.81 ± 30.59 for NP group. Mean TSI for P-CRC was 24.95 ± 8.90 and 22.74 ± 8.79 for NP group. Mean SF 308.09 ± 536.32 for P-CRC and 177.55 ± 159.95 for NP group. In a multivariate logistic regression analysis, only male gender (odds ratio (OR) = 2.04, 1.29–3.22), SF (OR = 1.001, 1.0004–1.003) and Fe (OR = 1.01, 1.004–1.02) were related with the presence of CRC and adenoma. Men gender and raised serum iron biomarkers increase the risk of P-CRC.
Literature
1.
go back to reference Chua ACG, Klopcic B, Lawrance IC, Olynyk JK, Trinder D. Iron: an emerging factor in colorectal carcinogenesis. World J Gastroenterol. 2010;16:663–72.CrossRefPubMedPubMedCentral Chua ACG, Klopcic B, Lawrance IC, Olynyk JK, Trinder D. Iron: an emerging factor in colorectal carcinogenesis. World J Gastroenterol. 2010;16:663–72.CrossRefPubMedPubMedCentral
3.
go back to reference Chen W, Zhao H, Li T, Yao H. HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis. Tumor Biol. 2013;34:2255–9.CrossRef Chen W, Zhao H, Li T, Yao H. HFE gene C282Y variant is associated with colorectal cancer in Caucasians: a meta-analysis. Tumor Biol. 2013;34:2255–9.CrossRef
4.
go back to reference Fargion S, Valenti L, Fracanzani AL. Hemochromatosis gene (HFE) mutations and cancer risk: expanding the clinical manifestations of hereditary iron overload. Hepatology. 2010;51:1119–21.CrossRefPubMed Fargion S, Valenti L, Fracanzani AL. Hemochromatosis gene (HFE) mutations and cancer risk: expanding the clinical manifestations of hereditary iron overload. Hepatology. 2010;51:1119–21.CrossRefPubMed
5.
go back to reference Fonseca-Nunes A, Jakszyn P, Agudo A. Iron and cancer risk—a systematic review and meta-analysis of the epidemiological evidence. Cancer Epidemiol Biomarkers Prev. 2014;23:12–31.CrossRefPubMed Fonseca-Nunes A, Jakszyn P, Agudo A. Iron and cancer risk—a systematic review and meta-analysis of the epidemiological evidence. Cancer Epidemiol Biomarkers Prev. 2014;23:12–31.CrossRefPubMed
6.
go back to reference Ekblom K, Marklund SL, Palmqvist R, Van Guelpen B, Hallmans G, Weinehall L, et al. Iron biomarkers in plasma, HFE genotypes, and risk for colorectal cancer in a prospective setting. Dis Col Rectum. 2012;55:337–44.CrossRef Ekblom K, Marklund SL, Palmqvist R, Van Guelpen B, Hallmans G, Weinehall L, et al. Iron biomarkers in plasma, HFE genotypes, and risk for colorectal cancer in a prospective setting. Dis Col Rectum. 2012;55:337–44.CrossRef
8.
go back to reference Osborne NJ, Gurrin LC, Allen KJ, Constantine CC, Delatycki MB, McLaren CE, et al. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010;51:1311–18.CrossRefPubMed Osborne NJ, Gurrin LC, Allen KJ, Constantine CC, Delatycki MB, McLaren CE, et al. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010;51:1311–18.CrossRefPubMed
9.
go back to reference Asberg A, Thorstensen K, Irgens WO, Romundstad PR, Hveem K. Cancer risk in HFE C282Y homozygotes: results from the HUNT 2 study. Scand J Gastroenterol. 2013;48:189–95.CrossRefPubMed Asberg A, Thorstensen K, Irgens WO, Romundstad PR, Hveem K. Cancer risk in HFE C282Y homozygotes: results from the HUNT 2 study. Scand J Gastroenterol. 2013;48:189–95.CrossRefPubMed
10.
go back to reference Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG. Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis. J Intern Med. 2012;27:51–63.CrossRef Ellervik C, Tybjaerg-Hansen A, Nordestgaard BG. Risk of cancer by transferrin saturation levels and haemochromatosis genotype: population-based study and meta-analysis. J Intern Med. 2012;27:51–63.CrossRef
11.
go back to reference Altés A, Gimferrer E, Capella G, Barceló MJ, Baiget M. Colorectal cancer and HFE mutations. Haematologica. 1999;84:479–80.PubMed Altés A, Gimferrer E, Capella G, Barceló MJ, Baiget M. Colorectal cancer and HFE mutations. Haematologica. 1999;84:479–80.PubMed
12.
go back to reference Beckman LE, Van Landenghem GF, Sikstrom C, Wahlin A, Markevarn B, Hallmans G, et al. Interaction between haemochromatosis and transferrin receptor in different neoplastic disorders. Carcinogenesis. 1999;20:1231–3.CrossRefPubMed Beckman LE, Van Landenghem GF, Sikstrom C, Wahlin A, Markevarn B, Hallmans G, et al. Interaction between haemochromatosis and transferrin receptor in different neoplastic disorders. Carcinogenesis. 1999;20:1231–3.CrossRefPubMed
13.
go back to reference MacDonald GA, Tarish J, Whitehall VJL, McCann SJ, Mellick GD, Buttenshaw RL, et al. No evidence of increased risk of colorectal cancer in individuals heterozygous for the cys282Tyr haemochromatosis mutation. J Gastroenterol Hepatol. 1999;14:1188–91.CrossRefPubMed MacDonald GA, Tarish J, Whitehall VJL, McCann SJ, Mellick GD, Buttenshaw RL, et al. No evidence of increased risk of colorectal cancer in individuals heterozygous for the cys282Tyr haemochromatosis mutation. J Gastroenterol Hepatol. 1999;14:1188–91.CrossRefPubMed
14.
go back to reference Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, et al. Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst. 2003;95:154–9.CrossRefPubMed Shaheen NJ, Silverman LM, Keku T, Lawrence LB, Rohlfs EM, Martin CF, et al. Association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst. 2003;95:154–9.CrossRefPubMed
15.
go back to reference Sullivan JL. Re: association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst. 2003;95:829–30.CrossRefPubMed Sullivan JL. Re: association between hemochromatosis (HFE) gene mutation carrier status and the risk of colon cancer. J Natl Cancer Inst. 2003;95:829–30.CrossRefPubMed
16.
go back to reference Robinson JP, Johnson VL, Rogers PA, Houlston RS, Maher ER, Bishop DT, et al. Evidence for an association between compound heterozygosity for germ line mutations in the hemochromatosis (HFE) gene and increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1460–3.CrossRefPubMed Robinson JP, Johnson VL, Rogers PA, Houlston RS, Maher ER, Bishop DT, et al. Evidence for an association between compound heterozygosity for germ line mutations in the hemochromatosis (HFE) gene and increased risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1460–3.CrossRefPubMed
17.
go back to reference Shi Z, Johnstone D, Talseth-Palmer B, Evans T-J, Spigelman AD, Groombridge C, et al. Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age. Int J Cancer. 2009;125:78–83.CrossRefPubMed Shi Z, Johnstone D, Talseth-Palmer B, Evans T-J, Spigelman AD, Groombridge C, et al. Haemochromatosis HFE gene polymorphisms as potential modifiers of hereditary nonpolyposis colorectal cancer risk and onset age. Int J Cancer. 2009;125:78–83.CrossRefPubMed
18.
go back to reference DL V d A, van der Hel O, Roest M, van der Schouw YT, van Gils CH, Marx JJM, et al. Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands). Cancer Causes Control. 2003;14:541–5.CrossRef DL V d A, van der Hel O, Roest M, van der Schouw YT, van Gils CH, Marx JJM, et al. Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands). Cancer Causes Control. 2003;14:541–5.CrossRef
19.
go back to reference McGlynn KA, Sakoda LC, Hu Y, Schoen RE, Bresalier RS, Yeager M, et al. Hemochromatosis gene mutations and distal adenomatous colorectal polyps. Cancer Epidemiol Biomarkers Prev. 2005;14:158–63.CrossRefPubMed McGlynn KA, Sakoda LC, Hu Y, Schoen RE, Bresalier RS, Yeager M, et al. Hemochromatosis gene mutations and distal adenomatous colorectal polyps. Cancer Epidemiol Biomarkers Prev. 2005;14:158–63.CrossRefPubMed
20.
go back to reference Chan AT, Ma J, Tranah GJ, Giovannucci EL, Rifai N, Hunter DJ, et al. Hemochromatosis gene mutations, body iron stores, dietary iron and risk of colorectal adenoma in women. J Natl Cancer Inst. 2005;97:917–26.CrossRefPubMed Chan AT, Ma J, Tranah GJ, Giovannucci EL, Rifai N, Hunter DJ, et al. Hemochromatosis gene mutations, body iron stores, dietary iron and risk of colorectal adenoma in women. J Natl Cancer Inst. 2005;97:917–26.CrossRefPubMed
21.
go back to reference Portillo I, Idigoras I, Ojembarrena E, Arana E, Hurtado JL, Basurko R, et al. Lesions detected in a colorectal cancer screening program in the Basque Country: first round (2009–2011). Gastroenterol Hepatol. 2013;36:301–8.CrossRefPubMed Portillo I, Idigoras I, Ojembarrena E, Arana E, Hurtado JL, Basurko R, et al. Lesions detected in a colorectal cancer screening program in the Basque Country: first round (2009–2011). Gastroenterol Hepatol. 2013;36:301–8.CrossRefPubMed
22.
go back to reference De Juan MD, Reta A, Castiella A, Pozueta J, Prada A, Cuadrado E. HFE gene mutation analysis in Basque hereditary hemochromatosis patients and controls. Eur J Hum Genet. 2001;9:961–4.CrossRefPubMed De Juan MD, Reta A, Castiella A, Pozueta J, Prada A, Cuadrado E. HFE gene mutation analysis in Basque hereditary hemochromatosis patients and controls. Eur J Hum Genet. 2001;9:961–4.CrossRefPubMed
23.
go back to reference Parra-Blanco A, Nicolás-Pérez D, Gimeno-García A, Grosso B, Jimenez A, Ortega J, et al. The timing of bowel preparation before colonoscopy determines the quality of cleansing, and is a significant factor contributing to the detection of flat lesions: a randomized study. World J Gastroenterol. 2006;14:6161–66.CrossRef Parra-Blanco A, Nicolás-Pérez D, Gimeno-García A, Grosso B, Jimenez A, Ortega J, et al. The timing of bowel preparation before colonoscopy determines the quality of cleansing, and is a significant factor contributing to the detection of flat lesions: a randomized study. World J Gastroenterol. 2006;14:6161–66.CrossRef
24.
go back to reference Lambert R, Kudo SE, Vieth M, Allen JI, Fujii H, Fujii T, et al. Pragmatic classification of superficial neoplastic colorectal lesions. Gastrointest Endosc. 2009;70:1182–99.CrossRefPubMed Lambert R, Kudo SE, Vieth M, Allen JI, Fujii H, Fujii T, et al. Pragmatic classification of superficial neoplastic colorectal lesions. Gastrointest Endosc. 2009;70:1182–99.CrossRefPubMed
25.
go back to reference Bastide NM, Pierre FHF, Corpet DE. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res. 2011;4:177–84.CrossRef Bastide NM, Pierre FHF, Corpet DE. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res. 2011;4:177–84.CrossRef
Metadata
Title
Gender and plasma iron biomarkers, but not HFE gene mutations, increase the risk of colorectal cancer and polyps
Authors
Agustin Castiella
Fernando Múgica
Eva Zapata
Leire Zubiaurre
Arantxa Iribarren
MªDolores de Juan
Luis Alzate
Ines Gil
Gregorio Urdapilleta
Pedro Otazua
José Ignacio Emparanza
Publication date
01-09-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 9/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3406-2

Other articles of this Issue 9/2015

Tumor Biology 9/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine