BMC Cancer 2006, 6:175 http://www.biomedcentral.com/1471-2407/6/175 Background Colorectal cancer (CRC) still is one of the leading causes of cancer deaths in developed countries and adenomas are the predominant precursors of this disease [1]. The risk of sporadic CRC is mainly associated with life- style factors and may be modulated by several genetic fac- tors of low penetrance [2,3]. Genetic variants represented by single nucleotide polymorphisms (SNPs) in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to CRC. To better understand what kind of impact, and at what stage in cancer progression certain SNPs contribute to CRC sus- ceptibility, implementing cases with both pre-malignant and malignant neoplasia in case-control studies may be valuable. Many published candidate gene association studies have assessed cancer risk by examining a single SNP per gene or a single locus at a time analysis approach. It has been sug- gested that use of haplotypes in association studies may have increased power over single-allele studies [4]. Haplo- type analyses take into account a number of tightly linked markers, which are much more informative than individ- ual markers. Haplotype analyses can identify unique chro- mosomal segments likely to harbor disease predisposing genes. Recently, a region in chromosome 19q13.2-3 encompassing the genes ERCC1, ASE-1 and RAI was iden- tified as a high-risk haplotype, defined as homozygous carriers of a haplotype consisting of ERCC1 Asn118AsnA, ASE-1 G-21AG and RAI IVS1 A4364GA. This haplotype consisting of three marker SNPs, is shown to be strongly associated with increased risk of skin cancer [5], breast cancer [6] and lung cancer [7] when compared to persons that are not homozygous carriers of the haplotype. No association has been observed with testicular cancer [8]. It is possible that this high-risk haplotype would be associ- ated with risk of colorectal cancer because it seems to be a marker of general mechanisms affecting several cancer forms. The region of chromosome 19 seems to be involved in the balance between growth and elimination of DNA damage and unwanted cells [8]. The ERCC1 gene encodes a subunit of the nucleotide exci- sion repair complex required for the incision step of nucleotide excision repair (NER) [9,10]. Since the ERCC1 protein is essential for NER and influence genomic insta- bility, polymorphisms in ERCC1 may play a role in car- cinogenesis. The ASE-1 gene (Anti Sense ERCC1) also called CD3EAP (CD3e antigen, epsilon polypeptide associated protein), encodes a nucleolar protein localized to fibrillar centers of the nucleolus and to the nucleolus organizer region of mitotic chromosomes [11]. The mouse homolog of ASE-1 is part of the RNA polymerase I complex [12]. The gene RAI (RelA-associated Inhibitor) also called iASSP and PPP1R13L, is an inhibitor of the RelA subunit of the transcription factor NF-κB [13]. The NF-κB plays a pivotal role in the inflammatory response and apoptosis. It is, therefore, likely that polymorphisms affecting the level or activity of the RelA-associated inhibitor RAI would influence the availability of RelA, and thus modify regulation of apoptosis. In the present paper, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas in a homogenous Norwegian cohort. In addition we investigated whether polymorphisms in these genes alone contributed to color- ectal adenoma and carcinoma risk. To the best of our knowledge this high-risk haplotype has not previously been studied in relation to colorectal adenomas or carci- nomas. Studying colorectal adenomas in addition to colorectal cancer may give information about the risk fac- tors in the earlier stages of carcinogenesis Methods The KAM cohort (Kolorektal cancer, arv og miljø) is based on the screening group of the Norwegian Colorectal Can- cer Prevention study (The NORCCAP study) in the county of Telemark [14], and a series of CRC cases operated on at Telemark Hospital (Skien) and Ulleval University Hospi- tal (Oslo). Those invited to participate in the NORCCAP study were 20,780 men and women, age 50–64 years old, drawn by randomization from the population registry in Oslo (urban) and the county of Telemark (mixed urban and rural). They were invited to have a flexible sigmoidos- copy screening examination with or without (1:1) an additional faecal occult blood test (FOBT). Seven hundred and seventy-seven individuals were excluded according to exclusion criteria. The overall attendance rate was 65%. The ID number for the NORCCAP study at ClinicalTri- als.gov is I [NCT00119912] [15]. The screened cases in the NORCCAP study selected for colonoscopy were invited to participate in the KAM study (1044 cases agreed). During a limited period of time, after the screening study of NORCCAP was well established, controls (polyp free by sigmoidoscopy) were invited to participate in the KAM study (400 controls agreed). Written consent was obtained from all the participants. The KAM cohort is based on an ethnic homogenous group of Norwegian ori- gin. The KAM biobank consists of blood and tissue samples from 160 CRC cases (16 identified in the NORCCAP screening group and 144 from hospitals), 1044 individu- Page 2 of 6 (page number not for citation purposes)