BMC Cancer 2006, 6:175 http://www.biomedcentral.com/1471-2407/6/175 (OR= 0.49, CI 0.21–1.13) and adenomas (OR = 0.70, CI 0.49–1.01). Vogel et al. [24] have shown that the RAI mRNA level is 41 % higher in lymphocytes from women compared to men, which may indicate that a gender dif- ference could be due to variation in transcription levels which subsequently result in differences in protein level. A possible explanation for our gender specific findings could be that women who are homozygous carriers of the haplotype have a defective apoptosis trigger (high levels of RAI). Colon cells with excessive DNA damage do not undergo apoptosis but survive with the potential of subse- quent malignant transformation. Very little is known about the function of ASE-1. White- head et al. [11] identified the ASE-1 gene product as a nucleolar protein by screening a HeLa cDNA library with a human autoimmune serum. The mouse Pol I-associated factor PAF49 shows striking homology to the human nucleolar protein ASE-1. Immunolocalization analysis revealed that PAF49 accumulated in the nucleolus of growing cells but dispersed to nucleoplasma in growth- arrested cells. These results strongly suggest that PAF49/ ASE-1 plays an important role in rRNA transcription [12]. Involvement in the immune function of this gene product has also been suggested [25]. We found that the observed risk estimate was highest among the heterozygote carriers, which may suggest that we detect an effect of another, linked polymorphism. The fact that we observe an effect for adenomas but not for colorectal cancer makes a chance finding possible. Another explanation for the observed association in the adenoma group only could be that the polymorphism may play a role in regression of adenomas rather than in progression to cancer. The CRC cases and controls have not been matched by age which may affect the results in a study. However, the con- trols were recruited from the same cohort as the adenoma and carcinoma cases. The adenoma cases and controls are from 50 to 64 years of age. Further, our controls have been screened and found polyp free and the risk of any of them having colon cancer at the time of inclusion is not very likely. Taking the number of statistical tests performed and the p- values we cannot exclude that our findings are due to chance. The relatively small numbers of the CRC cases limited our power to detect and association with carcino- mas. However, the findings for RAI are consistent with previous findings [5-8]. Conclusion The high-risk haplotype is not associated with increased risk of adenomas or colorectal cancer prior to gender strat- ification. When stratifying for gender, we did detect an effect in women and an inverse effect in men in relation to CRC cases, although not significant. Of the high-risk haplotype markers, the ASE-1 polymorphism was associ- ated with an increased risk of adenomas in women. The RAI polymorphism showed a trend towards risk reduction for both adenomas and carcinomas in women, although not significant. There was no significant association between the ERCC1 polymorphism and risk of colorectal adenomas and carcinomas. In conclusion we found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and ade- noma development in women. Competing interests The author(s) declare that they have no competing inter- ests. Authors' contributions CFS prepared samples for analysis and contributed with the data analysis. She prepared the first draft of the paper. MS prepared samples for analysis and contributed with the data analysis. She also contributed to the manuscript. ILH participated in collection and quality control of the questionnaires. UBV, HW and BAN genotyped the DNA samples. EHK brought the idea of the KAM study and organized it. All authors discussed the results, contributed to interpretation of the results and the final manuscript. Additional material Additional file 1 Table 2: Distributions of RAI, ASE-1 and ERCC1 genotypes and high- risk haplotype, and development of colorectal carcinomas and adeno- mas. The table presents the genotypic distribution of the three polymor- phisms in the RAI, ASE-1, and ERCC1 genes for both cases and controls, and the estimates of relative risk associated with the three polymorphisms as well as the predefined haplotype. Click here for file [http://www.biomedcentral.com/content/supplementary/1471- 2407-6-175-S1.pdf] Acknowledgements This study was supported by the Norwegian Cancer Society (Grant num- bers 51024/001 and E01-0851001), Telemark University College (Grant number 22069), the Norwegian Colorectal Cancer Prevention (NORC- CAP) study (Grants from the Norwegian Cancer Society and the Depart- ment of Health and Social Affairs), with the aid of EXTRA funds from the Norwegian Foundation for Health and Rehabilitation (2001/2/0110), East- ern Norway Regional Health Authority, the Danish Research Agency (Grant numbers 22-02-0356 and 2052-03-0016) and DRAGE, a grant from Danish Ministry of Health, Research Center for Environmental Health's Fund. Page 5 of 6 (page number not for citation purposes)