INTRODUCTION: About 20% of colorectal cancer (CRC) patients show some kind of familiarity, which might be caused by yet unknown combinations of low penetrance susceptibility genes. We aimed to identify genetic factors for familial CRC (fCRC) in a unique study design that includes phenotypic extremes as represented by fCRC cases and 'hyper-normal' controls without CRC history and no adenomatous polyps on colonoscopy. MATERIALS AND METHODS: Candidate gene variants were determined by allele-specific amplification (SLC10A2 c.169C>T and c.171G>T) and restriction fragment length polymorphism assays (CCND1 c.870A>G; CDH1 -160C>A; TP53 R72P; VDR T2M). In total, 98 patients with fCRC, 96 patients with sporadic CRC, and 220 hyper-normal controls were included. RESULTS: The minor allele of the CDH1 -160C>A polymorphism occurred significantly more often in controls compared to fCRC cases (OR = 0.664; p = 0.042). Homozygosity of the minor allele was significantly associated with affiliation to the control group (OR = 0.577; p = 0.029), indicating that both heterozygous and homozygous carriers of the common allele are at-risk for CRC. With respect to the CCND1 c.870A>G mutation, comparison of fCRC and sporadic CRC cases showed that A/A homozygosity was more common than G/G homozygosity among fCRC patients compared to controls (OR = 2.119; p = 0.045). However, no differences in allele or genotype frequencies were detected between sporadic CRC cases and controls, and no associations were observed for SLC10A2, TP53, and VDR polymorphisms. CONCLUSIONS: We report a potential association of variants in the CCND1 and CDH1 genes with fCRC using a unique study design with phenotypic extremes.
INTRODUCTION: About 20% of colorectal cancer (CRC) patients show some kind of familiarity, which might be caused by yet unknown combinations of low penetrance susceptibility genes. We aimed to identify genetic factors for familial CRC (fCRC) in a unique study design that includes phenotypic extremes as represented by fCRC cases and 'hyper-normal' controls without CRC history and no adenomatous polyps on colonoscopy. MATERIALS AND METHODS: Candidate gene variants were determined by allele-specific amplification (SLC10A2 c.169C>T and c.171G>T) and restriction fragment length polymorphism assays (CCND1 c.870A>G; CDH1 -160C>A; TP53R72P; VDR T2M). In total, 98 patients with fCRC, 96 patients with sporadic CRC, and 220 hyper-normal controls were included. RESULTS: The minor allele of the CDH1 -160C>A polymorphism occurred significantly more often in controls compared to fCRC cases (OR = 0.664; p = 0.042). Homozygosity of the minor allele was significantly associated with affiliation to the control group (OR = 0.577; p = 0.029), indicating that both heterozygous and homozygous carriers of the common allele are at-risk for CRC. With respect to the CCND1 c.870A>G mutation, comparison of fCRC and sporadic CRC cases showed that A/A homozygosity was more common than G/G homozygosity among fCRC patients compared to controls (OR = 2.119; p = 0.045). However, no differences in allele or genotype frequencies were detected between sporadic CRC cases and controls, and no associations were observed for SLC10A2, TP53, and VDR polymorphisms. CONCLUSIONS: We report a potential association of variants in the CCND1 and CDH1 genes with fCRC using a unique study design with phenotypic extremes.
Authors: T Ochsenkühn; E Bayerdörffer; A Meining; M Schinkel; C Thiede; V Nüssler; M Sackmann; R Hatz; A Neubauer; G Paumgartner Journal: Cancer Date: 1999-04-15 Impact factor: 6.860
Authors: W Wang; S Xue; S A Ingles; Q Chen; A T Diep; H D Frankl; A Stolz; R W Haile Journal: Cancer Epidemiol Biomarkers Prev Date: 2001-09 Impact factor: 4.254
Authors: Haixin Lei; Sara Sjöberg-Margolin; Sima Salahshor; Barbro Werelius; Eva Jandáková; Kari Hemminki; Annika Lindblom; Igor Vorechovský Journal: Int J Cancer Date: 2002-03-10 Impact factor: 7.396
Authors: José G Guillem; Beth S Rapaport; Tomas Kirchhoff; Prema Kolachana; Khedoudja Nafa; Emily Glogowski; Rob Finch; Helen Huang; William D Foulkes; Arnold Markowitz; Nathan A Ellis; Kenneth Offit Journal: J Am Coll Surg Date: 2003-02 Impact factor: 6.113
Authors: Nora Manoukian Forones; Jacqueline Miranda de Lima; Lessileia Gomes de Souza; Ismael Dale Cotrim Guerreiro da Silva Journal: J Gastrointest Cancer Date: 2009-04-17