PURPOSE: Whereas truncating germline mutations of the adenomatous polyposis coli (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of APC may confer a weaker risk for colorectal cancer. METHODS: We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas. Missense adenomatous polyposis coli alterations identified in this colorectal cancer multiple-polyp population were analyzed in a population-based series of patients with colorectal cancer and healthy control subjects. RESULTS: Germline APC or mutY human homologue (MYH) alterations were identified in 16 of 39 colorectal cancer-multiple polyp patients. Four missense APC gene alterations (S130G, E1317Q, D1822V, G2502S) were observed in 13 individuals and 3 additional patients carried presumed pathogenic (APC Y94X, biallelic MYH Y165C and heterozygous MYH G382D) mutations. When independently assessed in 971 patients with colorectal cancer and 954 healthy control subjects, none of the identified missense APC alterations conferred a significantly increased risk for colorectal cancer, odds ratio (95 percent confidence intervals): S130G = 3.1 (0.29-32.25), E1317Q = 1.08 (0.59-2.74), G2502S = 1 (0.65-1.63), D1822V (heterozygous) = 0.79 (0.64-0.98), D1822V (homozygous) = 0.82 (0.63-1.27). CONCLUSIONS: Germline missense APC alterations observed in 33 percent of patients with multiple colorectal neoplasms seemed to play a limited role in colorectal cancer risk when independently assessed by a population-based, case-control analysis.
PURPOSE: Whereas truncating germline mutations of the adenomatous polyposis coli (APC) gene give rise to familial adenomatous polyposis, missense polymorphisms of APC may confer a weaker risk for colorectal cancer. METHODS: We sequenced the entire open reading frame of the APC gene and tested for two common MYH mutations in a population-based series of patients with colorectal cancer and 5 to 99 adenomas. Missense adenomatous polyposis coli alterations identified in this colorectal cancer multiple-polyp population were analyzed in a population-based series of patients with colorectal cancer and healthy control subjects. RESULTS: Germline APC or mutY human homologue (MYH) alterations were identified in 16 of 39 colorectal cancer-multiple polyppatients. Four missense APC gene alterations (S130G, E1317Q, D1822V, G2502S) were observed in 13 individuals and 3 additional patients carried presumed pathogenic (APCY94X, biallelic MYHY165C and heterozygous MYHG382D) mutations. When independently assessed in 971 patients with colorectal cancer and 954 healthy control subjects, none of the identified missense APC alterations conferred a significantly increased risk for colorectal cancer, odds ratio (95 percent confidence intervals): S130G = 3.1 (0.29-32.25), E1317Q = 1.08 (0.59-2.74), G2502S = 1 (0.65-1.63), D1822V (heterozygous) = 0.79 (0.64-0.98), D1822V (homozygous) = 0.82 (0.63-1.27). CONCLUSIONS: Germline missense APC alterations observed in 33 percent of patients with multiple colorectal neoplasms seemed to play a limited role in colorectal cancer risk when independently assessed by a population-based, case-control analysis.
Authors: Julia A Knight; Heather J Sutherland; Gordon Glendon; Norman F Boyd; Irene L Andrulis Journal: Ann Epidemiol Date: 2002-01 Impact factor: 3.797
Authors: L A Boardman; S Schmidt; N M Lindor; L J Burgart; J M Cunningham; T Price-Troska; K Snow; D A Ahlquist; S N Thibodeau Journal: Genes Chromosomes Cancer Date: 2001-02 Impact factor: 5.006
Authors: H Lamlum; N Al Tassan; E Jaeger; I Frayling; O Sieber; F B Reza; M Eckert; A Rowan; E Barclay; W Atkin; C Williams; J Gilbert; J Cheadle; J Bell; R Houlston; W Bodmer; J Sampson; I Tomlinson Journal: Hum Mol Genet Date: 2000-09-22 Impact factor: 6.150
Authors: M Cotterchio; G McKeown-Eyssen; H Sutherland; G Buchan; M Aronson; A M Easson; J Macey; E Holowaty; S Gallinger Journal: Chronic Dis Can Date: 2000
Authors: K Heinimann; A Thompson; A Locher; T Furlanetto; E Bader; A Wolf; R Meier; K Walter; P Bauerfeind; G Marra; H Müller; D Foernzler; Z Dobbie Journal: Cancer Res Date: 2001-10-15 Impact factor: 12.701