Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Nov 7:8:326.
doi: 10.1186/1471-2407-8-326.

Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study

Sébastien Küry  1 , Bruno Buecher, Sébastien Robiou-du-Pont, Catherine Scoul, Hélène Colman, Tanguy Le Neel, Claire Le Houérou, Roger Faroux, Jean Ollivry, Bernard Lafraise, Louis-Dominique Chupin, Véronique Sébille, Stéphane Bézieau
Affiliations

Low-penetrance alleles predisposing to sporadic colorectal cancers: a French case-controlled genetic association study

Sébastien Küry et al. BMC Cancer. .

Abstract

Background: Sporadic colorectal cancers (CRC) are multifactorial diseases resulting from the combined effects of numerous genetic, environmental and behavioral risk factors. Genetic association studies have suggested low-penetrance alleles of extremely varied genes to be involved in susceptibility to CRC in Caucasian populations.

Methods: Through a large genetic association study based on 1023 patients with sporadic CRC and 1121 controls, we tested a panel of these low-penetrance alleles to find out whether they could determine "genotypic profiles" at risk for CRC among individuals of the French population. We examined 52 polymorphisms of 35 genes - drawn from inflammation, xenobiotic detoxification, one-carbon, insulin signaling, and DNA repair pathways - for their possible contribution to colorectal carcinogenesis. The risk of cancer associated with these polymorphisms was assessed by calculation of odds ratios (OR) using multivariate analyses and logistic regression.

Results: Whereas all these polymorphisms had previously been found to be associated with CRC risk, especially in Caucasian populations, we were able to replicate the association for only five of them. Three SNPs were shown to increase CRC risk: PTGS1 c.639C>A (p.Gly213Gly), IL8 c.-352T>A, and MTHFR c.1286A>C (p.Ala429Glu). On the contrary, two other SNPs, PLA2G2A c.435+230C>T and PPARG c.1431C>T (p.His477His), were associated with a decrease in CRC risk. Further analyses highlighted genotypic combinations having a greater predisposing effect on CRC (OR 1.97, 95%CI 1.31-2.97, p = 0.0009) than the allelic variants that were examined separately.

Conclusion: The identification of CRC-predisposing combinations, composed of alleles PTGS1 c.639A, PLA2G2A c.435+230C, PPARG c.1431C, IL8 c.-352A, and MTHFR c.1286C, highlights the importance of inflammatory processes in susceptibility to sporadic CRC, as well as a possible crosstalk between inflammation and one-carbon pathways.

PubMed Disclaimer

References

    1. Remontet L, Esteve J, Bouvier AM, Grosclaude P, Launoy G, Menegoz F, Exbrayat C, Tretare B, Carli PM, Guizard AV, Troussard X, Bercelli P, Colonna M, Halna JM, Hedelin G, Mace-Lesec'h J, Peng J, Buemi A, Velten M, Jougla E, Arveux P, Le Bodic L, Michel E, Sauvage M, Schvartz C, Faivre J. Cancer incidence and mortality in France over the period 1978–2000. Rev Epidemiol Sante Publique. 2003;51:3–30. - PubMed
    1. de la Chapelle A. Genetic predisposition to colorectal cancer. Nat Rev Cancer. 2004;4:769–780. doi: 10.1038/nrc1453. - DOI - PubMed
    1. Davidson NO. Genetic testing in colorectal cancer: who, when, how and why. Keio J Med. 2007;56:14–20. doi: 10.2302/kjm.56.14. - DOI - PubMed
    1. Hunter DJ, Riboli E, Haiman CA, Albanes D, Altshuler D, Chanock SJ, Haynes RB, Henderson BE, Kaaks R, Stram DO, Thomas G, Thun MJ, Blanche H, Buring JE, Burtt NP, Calle EE, Cann H, Canzian F, Chen YC, Colditz GA, Cox DG, Dunning AM, Feigelson HS, Freedman ML, Gaziano JM, Giovannucci E, Hankinson SE, Hirschhorn JN, Hoover RN, Key T, et al. A candidate gene approach to searching for low-penetrance breast and prostate cancer genes. Nat Rev Cancer. 2005;5:977–985. doi: 10.1038/nrc1754. - DOI - PubMed
    1. Goodman JE, Mechanic LE, Luke BT, Ambs S, Chanock S, Harris CC. Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis. Int J Cancer. 2006;118:1790–1797. doi: 10.1002/ijc.21523. - DOI - PMC - PubMed

Publication types