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Multicenter Study
. 2017 Oct 30;18(1):122.
doi: 10.1186/s12881-017-0485-5.

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

Jéssica Alonso-Molero  1 , Carmen González-Donquiles  2 , Camilo Palazuelos  3 , Tania Fernández-Villa  1 , Elena Ramos  1 , Marina Pollán  4   5 , Nuria Aragonés  4   5 , Javier Llorca  3   4 , M Henar Alonso  4   6   7   8 , Adonina Tardón  4   9 , Pilar Amiano  4   10 , José Juan Jiménez Moleon  4   11 , Rosana Peiró Pérez  4   12 , Rocío Capelo  13 , Antonio J Molina  1 , Inés Gómez Acebo  3   4 , Marcela Guevara  10 , Beatriz Perez-Gomez  4   5   14 , Virginia Lope  4   5 , José María Huerta  4   15 , Gemma Castaño-Vinyals  4   16   17   18 , Manolis Kogevinas  4   16   17   18   19 , Victor Moreno  4   6   7   8 , Vicente Martín  4   20
Affiliations
Multicenter Study

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

Jéssica Alonso-Molero et al. BMC Med Genet. .

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.

Keywords: Colorectal cancer; Gene-environment; Mediterranean diet; SMAD7; rs4939827.

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Conflict of interest statement

Ethics approval and consent to participate

The protocol of MCC-Spain was approved by the Ethics committees of the participating institutions. All participants were informed about the study objectives and signed an informed consent. Confidentiality of data is secured removing personal identifiers in the datasets. The database was registered in the Spanish Agency for Data Protection, number 2102672171. Permission to use the study database will be granted to researchers outside the study group, after revision and approval of each request by the Steering Committee.

More details on the organization of the project can be found online at http://www.mccspain.org.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Signaling pathway TGFβ-SMAD
Fig. 2
Fig. 2
Algorithm for cases and controls for this study, selected from the population which participated in the project
Fig. 3
Fig. 3
Association between SNP rs4939827 and the Mediterranean dietary pattern adherence in relation with colorectal cancer taking into account the genotype. Reference: TT genotype. Vertical axis: Adjusted Odd Ratio (The adjusted odds ratios (OR) was calculating taking into account the variables sex, age, socioeconomic level, BMI, total energy intake, family history fist degree, METS and area was used as random variable). Abscissa axis: Mediterranean Diet Pattern Adherence
See this image and copyright information in PMC

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