Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

<p>Abstract</p> <p>Background</p> <p>CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility.</p> <p>Methods</p> <p>We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls.</p> <p>Results</p> <p>The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect.</p> <p>Conclusion</p> <p>Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.</p

Inflammatory response gene polymorphisms and their relationship with colorectal cancer risk

<p>Abstract</p> <p>Backgroud</p> <p>Patients with chronic inflammatory bowel disease (IBD) are at an increased risk of colorectal cancer (CRC) and it is estimated that one in six persons diagnosed with IBD will develop CRC. This fact suggests that genetic variations in inflammatory response genes may act as CRC disease risk modifiers.</p> <p>Methods</p> <p>In order to test this hypothesis we investigated a series of polymorphisms in 6 genes (NOD2, DLG5, OCTN1, OCTN2, IL4, TNFα) associated with the inflammatory response on a group of 607 consecutive newly diagnosed colorectal cancer patients and compared the results to controls (350 consecutive newborns and 607 age, sex and geographically matched controls).</p> <p>Results</p> <p>Of the six genes only one polymorphism in TNFα(-1031T/T) showed any tendency to be associated with disease risk (64.9% for controls and 71.4% for CRC) which we further characterized on a larger cohort of CRC patients and found a more profound relationship between the TNFα -1031T/T genotype and disease (64.5% for controls vs 74.7% for CRC cases above 70 yrs). Then, we investigated this result and identified a suggestive tendency, linking the TNFα -1031T/T genotype and a previously identified change in the CARD15/NOD2 gene (OR = 1.87; p = 0,02 for CRC cases above 60 yrs).</p> <p>Conclusion</p> <p>The association of polymorphisms in genes involved in the inflammatory response and CRC onset suggest that there are genetic changes capable of influencing disease risk in older persons.</p

Clinical characteristics of tumors derived from colorectal cancer patients who harbor the Tumor Necrosis Factor beta-1031T/T and NOD2 3020insC polymorphism

Background: Genetic predispositions to disease have focused on highly penetrant causative changes in tumor suppressor genes or genes associated with DNA mismatch repair. New investigations are revealing new genetic associations with disease that are more subtle in their association with disease and require characterization. Methods: In this report we have examined the tumor characteristics in a group of patients who have been shown to harbor two polymorphisms in two genes that are associated with the immune system NOD2 and TNFα. Results: Colorectal cancers from patients with NOD2 3020insC and TNFα-1031T/T constitutional changes are mostly right-sided disease (OR = 2.21, p = 0.03) with a tendency to higher stages (OR = 2.41, p = 0.06), increased number of associated polyps (OR = 1.77, p = 0.16) and later age of average age of disease onset (p = 0.039). Conclusion: The results reveal that there appear to be specific characteristics associated with the tumors that may aid in determining management strategies to reduce the risk of disease