BMC Cancer 2006, 6:175 http://www.biomedcentral.com/1471-2407/6/175 als identified with adenomas in the large intestine (991 high- and low-risk adenomas, 53 hyperplastic polyps) and 400 controls, defined as individuals with normal findings at flexible sigmoidoscopy screening. Adenoma cases and controls were all drawn from the NORCCAP study. All of the participants completed a questionnaire on demographics, health status, dietary, and smoking habits, alcohol consumption, physical exercise and occu- pation. The questionnaire contained information on a family history of adenomas and carcinomas, and the included cases and controls had no known personal his- tory of genetic predisposition. The adenocarcinomas were collected prior to chemo- or radiotherapy treatment. Two specialist histopathologists examined the histology of the adenomas independently in order to determine the tumor stage as mild, moderate or severe dysplasia. They reached the same conclusion in all cases. The KAM study is approved by the Regional Ethics Committee and the Data Inspectorate. In the present study we analyzed available blood samples from 156 cases with adenocarcinoma, 981 cases with ade- nomas, (i.e. 227 high-risk and 754 low-risk adenomas) and 399 controls. The 53 hyperplastic polyps were not included in the analysis. Diminished numbers of availa- ble cases in the KAM biobank and analyzed cases are due to loss of samples during preparation and/or lack of infor- mation from questionnaires. A high-risk adenoma is defined as an adenoma measuring = 10 mm in diameter and/or with villous components and/or showing severe dysplasia [14]. The distribution of gender and age among controls and cases with colonic carcinomas and adeno- mas are shown in Table 1. Genomic DNA was isolated from blood samples accord- ing to standard procedures [16] with minor modifications as previously described [17]. Genotypes were determined on an ABI 7500 using end- point readings or on a light cycler (Roche Molecular Bio- chemicals, Mannheim, Germany). ERCC1 Asn118Asn (rs#3177700) was determined on a light cycler as described [6].ASE-1 G-21A (rs#967591) was determined using the primers 5'-TCT GCA ACC TGG TGC GAG-3', 5'- CCT TTC TCC TTC CAC CAA CG-3' and the probes G- allele: 5'-FAM- AGG GTT GCC TGA GGT GTG GGT CC- BHQ, A-allele: Yakima Yellow- AGG GTT ACC TGA GGT GTG GGT CC-BHQ-3'. The reactions were run for 40 cycles at 15 s at 94°C, 60 s at 62°C.RAI IVS1 A4364G (rs#1970764) was determined as described [8]. In gen- eral, 10 μl reactions contained ca. 50 ng DNA, 5 μl Mas- termix (Applied Biosystems, Birkerød, Denmark), 100 nM of each probe and 900 nM of each primer. Controls were included in each run, and 10 % of the samples were retyped with identical results. MiniTab Statistical Software, Release 13.1 Xtra (Minitab Inc.) and SPSS (Statistical Packages for the Social Sci- ences) 12.0.1 for Windows were used for the statistic cal- culations. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated using binary logistic regres- sion to assess the relationship between each polymor- phism and the colorectal adenoma or carcinoma cases. When, estimating OR for carriers of the haplotype the comparison group was all the other remaining individu- als, individuals who were not homozygous carriers of the high-risk haplotype. We have previously shown that nei- ther known heterozygotes nor possible heterozygotes are at increased risk of breast cancer. This strongly suggests that the haplotype is detecting a recessive marker. We have therefore chosen only to look at homozygous carriers' vs. the rest. All data are adjusted for age and gender. Smoking dose and alcohol intake were also included in the adjustment in the logistic regression analyses, but the results did not differ from those adjusted only for age and gender. Including smoking and alcohol parameters resulted in lower numbers of cases and controls due to missing data in the questionnaires. Due to this we choose to use the data adjusted only for age and gender. Table 1: Distributions of gender and age among controls and cases with colorectal carcinomas and adenomas. No. of subjects Sexa Male Female Ageb Mean (SD) Controls No (%) 399 157 (39.3) 242 (60.7) 54.2 (3.3) Carcinomas No (%) 156 86 (55.1) 70 (44.9) 67.9 (11.2) Adenomas, all No (%) 981 601 (61.3) 380 (38.7) 57.3 (3.7) High-risk adenomas No (%) Low-risk adenomas No (%) 227 150 (66.1) 77 (33.9) 57.3 (3.5) 754 451 (59.8) 303 (40.2) 57.3 (3.8) a There are significant differences in the number of males and females in the control group and the case groups, p < 10-4 (test for comparison of two proportions). b There are significant differences in age among the control group and the case groups, p < 10-4 (Mann-Whitney test). Page 3 of 6 (page number not for citation purposes)