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Published in: BMC Medical Genetics 1/2017

Open Access 01-12-2017 | Research article

The RS4939827 polymorphism in the SMAD7 GENE and its association with Mediterranean diet in colorectal carcinogenesis

Authors: Jéssica Alonso-Molero, Carmen González-Donquiles, Camilo Palazuelos, Tania Fernández-Villa, Elena Ramos, Marina Pollán, Nuria Aragonés, Javier Llorca, M. Henar Alonso, Adonina Tardón, Pilar Amiano, José Juan Jiménez Moleon, Rosana Peiró Pérez, Rocío Capelo, Antonio J. Molina, Inés Gómez Acebo, Marcela Guevara, Beatriz Perez-Gomez, Virginia Lope, José María Huerta, Gemma Castaño-Vinyals, Manolis Kogevinas, Victor Moreno, Vicente Martín

Published in: BMC Medical Genetics | Issue 1/2017

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Abstract

Background

The objective of our investigation is to study the relationship between the rs4939827 SNP in the SMAD7 gene, Mediterranean diet pattern and the risk of colorectal cancer.

Methods

We examined 1087 cases of colorectal cancer and 2409 population controls with available DNA samples from the MCC-Spain study, 2008–2012. Descriptive statistical analyses, and multivariate logistic mixed models were performed. The potential synergistic effect of rs4939827 and the Mediterranean diet pattern was evaluated with logistic regression in different strata of of adherence to the Mediterranean diet and the genotype.

Results

High adherence to Mediterrenean diet was statistically significantly associated with colorectal cancer risk. A decreased risk for CRC cancer was observed for the CC compared to the TT genotype (OR = 0.65 and 95% CI = 0.51–0.81) of the rs4939827 SNP Also, we could show an association between the Mediterranean diet pattern (protective factor) and rs4939827. Although the decreased risk for the CC genotype was slightly more pronounced in subjects with high adherence to Mediterrenean diet, there was no statistically significant synergistic effect between genotype CC and adherence to the Mediterranean dietary pattern factors.

Conclusion

The SMAD7 gene and specifically the allele C could be protective for colorectal cancer. An independent protective association was also observed between high adherence Mediterranean diet pattern and CRC risk. Findings form this study indicate that high adherence to Mediterranean diet pattern has a protective role for CRC cancer probably involving the Tumor Growth Factor- β pathway in this cancer.
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Literature
2.
go back to reference Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomark Prev. 2009;18(6):1688–94.CrossRef Center MM, Jemal A, Ward E. International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomark Prev. 2009;18(6):1688–94.CrossRef
3.
go back to reference Hu X, Feng F, Li X, Yuan P, Luan R, Yan J, et al. Gene polymorphisms related to insulin resistance and gene-environment interaction in colorectal cancer risk. Ann Hum Biol. 2015;42(6):560–8.PubMed Hu X, Feng F, Li X, Yuan P, Luan R, Yan J, et al. Gene polymorphisms related to insulin resistance and gene-environment interaction in colorectal cancer risk. Ann Hum Biol. 2015;42(6):560–8.PubMed
4.
go back to reference Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, et al. Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ. BMJ Publishing Group; 2015 Oct 6;351:h4970. Ait Ouakrim D, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, et al. Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ. BMJ Publishing Group; 2015 Oct 6;351:h4970.
5.
go back to reference Pérez-Jiménez J, Elena Díaz-Rubio M, Saura-Calixto F. Contribution of macromolecular antioxidants to dietary antioxidant capacity: a study in the Spanish Mediterranean diet. Plant Foods Hum Nutr. 2015 Dec 20;70(4):365–70.CrossRefPubMed Pérez-Jiménez J, Elena Díaz-Rubio M, Saura-Calixto F. Contribution of macromolecular antioxidants to dietary antioxidant capacity: a study in the Spanish Mediterranean diet. Plant Foods Hum Nutr. 2015 Dec 20;70(4):365–70.CrossRefPubMed
6.
go back to reference Schwingshackl L, Hoffmann G. Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies. Cancer Med. 2015;4(12):1933–47.CrossRefPubMedPubMedCentral Schwingshackl L, Hoffmann G. Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta-analysis of observational studies. Cancer Med. 2015;4(12):1933–47.CrossRefPubMedPubMedCentral
7.
go back to reference Rotelli MT, Bocale D, De Fazio M, Ancona P, Scalera I, Memeo R, et al. IN-VITRO evidence for the protective properties of the main components of the Mediterranean diet against colorectal cancer: a systematic review. Surg Oncol Elsevier Ltd. 2015;24(3):145–52.CrossRef Rotelli MT, Bocale D, De Fazio M, Ancona P, Scalera I, Memeo R, et al. IN-VITRO evidence for the protective properties of the main components of the Mediterranean diet against colorectal cancer: a systematic review. Surg Oncol Elsevier Ltd. 2015;24(3):145–52.CrossRef
8.
go back to reference Fung TT, Brown LS. Dietary patterns and the risk of colorectal cancer. Curr Nutr Rep. 2013;2(1):48–55.CrossRefPubMed Fung TT, Brown LS. Dietary patterns and the risk of colorectal cancer. Curr Nutr Rep. 2013;2(1):48–55.CrossRefPubMed
9.
go back to reference Frazier-Wood AC. Dietary patterns, genes, and health: challenges and obstacles to be overcome. Curr Nutr Rep. 2015;4(1):82–7.CrossRefPubMed Frazier-Wood AC. Dietary patterns, genes, and health: challenges and obstacles to be overcome. Curr Nutr Rep. 2015;4(1):82–7.CrossRefPubMed
11.
go back to reference Nguyen KA, Cao Y, Chen JR, Townsend Jr. CM, Ko TC. Dietary fiber enhances a tumor suppressor signaling pathway in the gut. Ann Surg. 2006;243(5):617–9.CrossRef Nguyen KA, Cao Y, Chen JR, Townsend Jr. CM, Ko TC. Dietary fiber enhances a tumor suppressor signaling pathway in the gut. Ann Surg. 2006;243(5):617–9.CrossRef
12.
go back to reference Kim YS. Milner J a. Dietary modulation of colon cancer risk. J Nutr. 2007;137:2576S–9S.PubMed Kim YS. Milner J a. Dietary modulation of colon cancer risk. J Nutr. 2007;137:2576S–9S.PubMed
13.
go back to reference Yan X, Liao H, Cheng M, Shi X, Lin X, Feng XH, et al. Smad7 protein interacts with receptor-regulated Smads (R-Smads) to inhibit transforming growth factor-B (TGF-B)/Smad signaling. J Biol Chem. 2016;291(1):382–92.CrossRefPubMed Yan X, Liao H, Cheng M, Shi X, Lin X, Feng XH, et al. Smad7 protein interacts with receptor-regulated Smads (R-Smads) to inhibit transforming growth factor-B (TGF-B)/Smad signaling. J Biol Chem. 2016;291(1):382–92.CrossRefPubMed
14.
go back to reference Castaño-Vinyals G, Aragonés N, Pérez-Gómez B, Martín V, Llorca J, Moreno V, et al. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design. Gac Sanit. Elsevier. 2015 Jul;29(4):308–15. Castaño-Vinyals G, Aragonés N, Pérez-Gómez B, Martín V, Llorca J, Moreno V, et al. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design. Gac Sanit. Elsevier. 2015 Jul;29(4):308–15.
15.
go back to reference García-Closas R, García-Closas M, Kogevinas M, Malats N, Silverman D, Serra C, et al. Food, nutrient and heterocyclic amine intake and the risk of bladder cancer. Eur J Cancer. 2007;43(11):1731–40.CrossRefPubMed García-Closas R, García-Closas M, Kogevinas M, Malats N, Silverman D, Serra C, et al. Food, nutrient and heterocyclic amine intake and the risk of bladder cancer. Eur J Cancer. 2007;43(11):1731–40.CrossRefPubMed
16.
go back to reference Cervera P, Farran A, Zamora-Ros R. Tablas de composición de alimentos CESNID = Taules de composició d’aliments del CESNID: Universitat de Barcelona; 2004. 247 p Cervera P, Farran A, Zamora-Ros R. Tablas de composición de alimentos CESNID = Taules de composició d’aliments del CESNID: Universitat de Barcelona; 2004. 247 p
17.
go back to reference Nöthlings U, Hoffman K, Boeing H. Do cross-check questions improve food frequency questionnaire data? IARC Sci Publ. 2002:23–5. Nöthlings U, Hoffman K, Boeing H. Do cross-check questions improve food frequency questionnaire data? IARC Sci Publ. 2002:23–5.
18.
go back to reference Calvert C, Cade J, Barrett JH, Woodhouse A. Using cross-check questions to address the problem of mis-reporting of specific food groups on food frequency questionnaires. UKWCS steering group. United Kingdom Women’s cohort study steering group. Eur J Clin Nutr. 1997;51(10):708–12.CrossRefPubMed Calvert C, Cade J, Barrett JH, Woodhouse A. Using cross-check questions to address the problem of mis-reporting of specific food groups on food frequency questionnaires. UKWCS steering group. United Kingdom Women’s cohort study steering group. Eur J Clin Nutr. 1997;51(10):708–12.CrossRefPubMed
19.
go back to reference Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score. Public Health Nutr. 2014;17(12):2769–82.CrossRefPubMed Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. Mediterranean diet and health status: an updated meta-analysis and a proposal for a literature-based adherence score. Public Health Nutr. 2014;17(12):2769–82.CrossRefPubMed
20.
go back to reference Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics Oxford University Press. 2006 Aug 1;22(15):1928–9. Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics Oxford University Press. 2006 Aug 1;22(15):1928–9.
21.
go back to reference Halder SK, Beauchamp RD, Datta PK. Smad7 induces tumorigenicity by blocking TGF-β-induced growth inhibition and apoptosis. Exp Cell Res. 2005;307(1):231–46.CrossRefPubMed Halder SK, Beauchamp RD, Datta PK. Smad7 induces tumorigenicity by blocking TGF-β-induced growth inhibition and apoptosis. Exp Cell Res. 2005;307(1):231–46.CrossRefPubMed
22.
go back to reference Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. Elsevier Ireland Ltd. 2013;335(1):168–74. Li Q, Zou C, Zou C, Han Z, Xiao H, Wei H, et al. MicroRNA-25 functions as a potential tumor suppressor in colon cancer by targeting Smad7. Cancer Lett. Elsevier Ireland Ltd. 2013;335(1):168–74.
23.
go back to reference Zhang B, Jia W, Matsuo K, Shin A, Xiang Y, Matsuda K, et al. Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in east Asians. Int J Cancer. 2014;135(4):948–55.CrossRefPubMedPubMedCentral Zhang B, Jia W, Matsuo K, Shin A, Xiang Y, Matsuda K, et al. Genome-wide association study identifies a new SMAD7 risk variant associated with colorectal cancer risk in east Asians. Int J Cancer. 2014;135(4):948–55.CrossRefPubMedPubMedCentral
24.
go back to reference Slattery ML, Herrick J, Curtin K, Samowitz W, Wolff RK, Caan BJ, et al. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res. 2010;70(4):1479–85.CrossRefPubMedPubMedCentral Slattery ML, Herrick J, Curtin K, Samowitz W, Wolff RK, Caan BJ, et al. Increased risk of colon cancer associated with a genetic polymorphism of SMAD7. Cancer Res. 2010;70(4):1479–85.CrossRefPubMedPubMedCentral
25.
go back to reference Thompson CL, Plummer SJ, Acheson LS, Tucker TC, Casey G, Li L. Association of common genetic variants in SMAD7 and risk of colon cancer. Carcinogenesis. 2009;30(6):982–6.CrossRefPubMedPubMedCentral Thompson CL, Plummer SJ, Acheson LS, Tucker TC, Casey G, Li L. Association of common genetic variants in SMAD7 and risk of colon cancer. Carcinogenesis. 2009;30(6):982–6.CrossRefPubMedPubMedCentral
26.
go back to reference Geng T-T, Xun X-J, Li S, Feng T, Wang L-P, Jin T-B, et al. Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population. World J Gastroenterol. 2015;21(22):6898–904.CrossRefPubMedPubMedCentral Geng T-T, Xun X-J, Li S, Feng T, Wang L-P, Jin T-B, et al. Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population. World J Gastroenterol. 2015;21(22):6898–904.CrossRefPubMedPubMedCentral
27.
go back to reference Jung KJ, Won D, Jeon C, Kim S, Kim T. Il, Jee SH, et al. a colorectal cancer prediction model using traditional and genetic risk scores in Koreans. BMC Genet. 2015;16(49):1–7. Jung KJ, Won D, Jeon C, Kim S, Kim T. Il, Jee SH, et al. a colorectal cancer prediction model using traditional and genetic risk scores in Koreans. BMC Genet. 2015;16(49):1–7.
28.
go back to reference Baert-Desurmont S, Charbonnier F, Houivet E, Ippolito L, Mauillon J, Bougeard M, et al. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk. Eur J Hum Genet. 2016;24(1):99–105.CrossRefPubMed Baert-Desurmont S, Charbonnier F, Houivet E, Ippolito L, Mauillon J, Bougeard M, et al. Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk. Eur J Hum Genet. 2016;24(1):99–105.CrossRefPubMed
29.
go back to reference Ho JW, Choi S, Lee Y, Hui TC, Cherny SS, Garcia-Barceló M-M, et al. Replication study of SNP associations for colorectal cancer in Hong Kong Chinese. Br J Cancer. 2011;104(2):369–75.CrossRefPubMed Ho JW, Choi S, Lee Y, Hui TC, Cherny SS, Garcia-Barceló M-M, et al. Replication study of SNP associations for colorectal cancer in Hong Kong Chinese. Br J Cancer. 2011;104(2):369–75.CrossRefPubMed
30.
go back to reference Tenesa A, Farrington SM, Prendergast JGD, Porteous ME, Walker M, Haq N, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet. 2008;40(5):631–7.CrossRefPubMedPubMedCentral Tenesa A, Farrington SM, Prendergast JGD, Porteous ME, Walker M, Haq N, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21. Nat Genet. 2008;40(5):631–7.CrossRefPubMedPubMedCentral
31.
go back to reference Tenesa A, Theodoratou E, Din FVN, Farrington SM, Cetnarskyj R, Barnetson RA, et al. Ten common genetic variants associated with colorectal cancer risk are not associated with survival after diagnosis. Clin Cancer Res. 2010;16(14):3754–9.CrossRefPubMedPubMedCentral Tenesa A, Theodoratou E, Din FVN, Farrington SM, Cetnarskyj R, Barnetson RA, et al. Ten common genetic variants associated with colorectal cancer risk are not associated with survival after diagnosis. Clin Cancer Res. 2010;16(14):3754–9.CrossRefPubMedPubMedCentral
32.
go back to reference Passarelli MN, Coghill AE, Hutter CM, Zheng Y, Makar KW, Potter JD, et al. Common colorectal cancer risk variants in SMAD7 are associated with survival among pre-diagnostic non-steroidal anti-inflammatory drug users: a population-based study of post-menopausal women. Genes Chromosom Cancer. 2011;50(11):875–86.CrossRefPubMedPubMedCentral Passarelli MN, Coghill AE, Hutter CM, Zheng Y, Makar KW, Potter JD, et al. Common colorectal cancer risk variants in SMAD7 are associated with survival among pre-diagnostic non-steroidal anti-inflammatory drug users: a population-based study of post-menopausal women. Genes Chromosom Cancer. 2011;50(11):875–86.CrossRefPubMedPubMedCentral
33.
go back to reference Yao K, Hua L, Wei L, Meng J, Correlation HJ. Between CASC8, SMAD7 polymorphisms and the susceptibility to colorectal cancer. Medicine (Baltimore). 2015;94(46):e1884.CrossRef Yao K, Hua L, Wei L, Meng J, Correlation HJ. Between CASC8, SMAD7 polymorphisms and the susceptibility to colorectal cancer. Medicine (Baltimore). 2015;94(46):e1884.CrossRef
Metadata
Title
The RS4939827 polymorphism in the SMAD7 GENE and its association with Mediterranean diet in colorectal carcinogenesis
Authors
Jéssica Alonso-Molero
Carmen González-Donquiles
Camilo Palazuelos
Tania Fernández-Villa
Elena Ramos
Marina Pollán
Nuria Aragonés
Javier Llorca
M. Henar Alonso
Adonina Tardón
Pilar Amiano
José Juan Jiménez Moleon
Rosana Peiró Pérez
Rocío Capelo
Antonio J. Molina
Inés Gómez Acebo
Marcela Guevara
Beatriz Perez-Gomez
Virginia Lope
José María Huerta
Gemma Castaño-Vinyals
Manolis Kogevinas
Victor Moreno
Vicente Martín
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2017
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-017-0485-5

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