Genetic polymorphisms of MMP1, MMP3 and MMP7 gene promoter and risk of colorectal adenoma

BACKGROUND: Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls. METHODS: Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression. RESULTS: No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression. CONCLUSION: These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis

Enquête de satisfaction auprès de patients atteints d'hépatite chronique C suivis par une infirmière (expérimentation sur le transfert de tâches au Centre Hospitallier de Montélimar [Drôme])

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Celiac disease is not associated with chronic hepatitis C.

International audienc

Low compliance with colonoscopic screening in first-degree relatives of patients with large adenomas.

International audienceBACKGROUND: Little is known about compliance with colonoscopy as a screening method in first-degree relatives of patients with large adenomas. Aims To evaluate the compliance with screening colonoscopy among this population, and its determinants. METHODS: Data were obtained from the family part of the GEADE study, a study on genetic factors of colorectal adenomas. Index cases were 306 patients with adenomas > or = 10 mm. All living first-degree relatives aged 40-75 who could be contacted by the index case were asked to undergo a colonoscopy, unless they had had one in the previous 5 years. RESULTS: Among 674 eligible relatives, 56 had had a colonoscopy within the preceding 5 years and 114 underwent a screening colonoscopy resulting in a compliance with screening colonoscopy of 18%. This was not related to most characteristics of index cases. Compliance was significantly lower when the index case lived in the Greater Paris area than when he/she lived in other areas (12% vs. 21%). It was higher in siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55 years old (22%) than in relatives aged 55 and over (15%). CONCLUSIONS: Compliance with colonoscopy was low in first-degree relatives of patients with large adenomas. The reasons for this should be determined and appropriate strategies developed to increase compliance

Colonoscopic screening of first-degree relatives of patients with large adenomas: increased risk of colorectal tumors.: Adenomas in relatives and colorectal tumor risk

International audienceBackground & Aims: The risk of developing colorectal neoplasia is not well established among family members of individuals with large adenomas and screening strategies remain under debate in this population. This study aimed at quantifying the risk of colorectal adenomas and cancers using colonoscopic screening in first-degree relatives of patients with large adenomas. Methods: This case-control study was performed in 18 endoscopic units of French non-University Hospitals. A colonoscopy was offered to first-degree relatives of 306 index cases with adenomas ≥ 10 mm, if they were alive, aged 40-75 and could be contacted by the index case. Among 674 relatives meeting these criteria, 168 were examined and matched for age, gender, and geographical area with two controls (n=307). Controls were randomly selected from 1362 consecutive patients aged 40-75 having undergone a colonoscopy for minor symptoms. Results: The overall prevalence of large adenomas was 8.4% and 4.2% in relatives and controls, respectively. Odds ratios (OR) associated with a history of large adenomas in relatives were 2.27 (95% confidence interval [CI]: 1.01-5.09) for cancers or large adenomas and 1.21 (95% CI: 0.68-2.15) for small adenomas, and 1.56 (95% CI: 0.96-2.53) for all colorectal neoplasia. The risk of large adenomas and cancers was higher in relatives of index cases younger than 60 years (OR: 3.82; 95% CI: 0.92-15.87) and when the index case had large distal adenomas (OR, 3.14; 95% CI: 1.27-7.73). Conclusion: First-degree relatives of patients with large adenomas are at increased risk of developing colorectal cancers or large adenomas. This result has implications for screening in this high-risk population

Analysis of Candidate Genes in Occurrence and Growth of Colorectal Adenomas

Predisposition to sporadic colorectal tumours is influenced by genes with minor phenotypic effects. A case-control study was set up on 295 patients treated for a large adenoma matched with polyp-free individuals on gender, age, and geographic origin in a 1 : 2 proportion. A second group of 302 patients treated for a small adenoma was also characterized to distinguish effects on adenoma occurrence and growth. We focussed the study on 38 single nucleotide polymorphisms (SNPs) encompassing 14 genes involved in colorectal carcinogenesis. Effect of SNPs was tested using unconditional logistic regression. Comparisons were made for haplotypes within a given gene and for biologically relevant genes combinations using the combination test. The APC p.Glu1317Gly variant appeared to influence the adenoma growth (P=.04, exact test) but not its occurrence. This result needs to be replicated and genome-wide association studies may be necessary to fully identify low-penetrance alleles involved in early stages of colorectal tumorigenesis