The 3020insC Allele of NOD2 Predisposes to Cancers of Multiple Organs

The NOD2 gene has been associated with susceptibility to Crohn's disease and individuals with Crohn's disease are at increased risk for cancer at a number of organ sites. We studied the association between the 3020insC allele of the NOD2 gene and cancer among 2604 cancer patients and 1910 controls from Poland. Patients were diagnosed with one of twelve types of cancer in the Szczecin region between 1994 and 2004. Significant associations were found for colon cancer (OR = 1.8; 95% CI 1.2 to 2.6), for lung cancer (OR = 1.7; 95% CI = 1.1 to 2.5) and for ovarian cancer (OR = 1.6; 95% CI 1.1 to 2.3). In addition, a significant association was found for early-onset laryngeal cancer (OR = 2.9; 95% CI 1.4 to 6.2) and for breast cancer in the presence of DCIS (OR = 2.1 95% CI = 1.2 to 3.6). The NOD2 3020insC allele is relatively common (in Poland 7.3% of individuals) and may be responsible for an important fraction of cancer cases. We estimate that the lifetime cancer risk among carriers of this allele is 30% higher than that of individuals with two wild-type alleles

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

New Fluorescence Probes for Biomolecules

Steady state fluorescence measurements have been used for the investigation of interaction between the bovine serum albumin (BSA) and fluorescence probes: 3-hydroxy-2,4- bis[(3-methyl-1,3-benzoxazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ6), 3-hydroxy- 2,4-bis[(3-methyl-1,3-benzothiazol-2(3H)-ylidene)methyl]cyclobut-2-en-1-one (SQ7) and 3-hydroxy-2,4-bis[(1,3,3-trimethyl-1,3-dihydro-2H-indol-2-ylidene)methyl]cyclobut-2-en-1-one (SQ8). The binding constant between bovine serum albumin and squarine dyes has been determined by using both the Benesi-Hildebrand and Stern-Volmer equations. The negative value of free energy change indicates the existence of a spontaneous complexation process of BSA with squarine dyes

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

Molecular basis of inherited predispositions for tumors*

On the basis of literature data and own experience the authors review the current knowledge about the molecular basis of inherited predispositions for tumors. They hypothesize that in the near perspective 5-10 years studies using existing registry data/material and the latest novel technology will allow the identification of the molecular background for the majority of hereditary cancers which will have enormous practical consequences especially for the prevention of malignancies