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Colorectal Cancer Syndrome (colorectal + cancer_syndrome)
Selected AbstractsMUTYH mutations associated with familial adenomatous polyposis: functional characterization by a mammalian cell-based assay,HUMAN MUTATION, Issue 2 2010Sara Molatore Abstract MUTYH -associated polyposis (MAP) is a colorectal cancer syndrome, due to biallelic mutations of MUTYH. This Base Excision Repair gene encodes for a DNA glycosylase that specifically mitigates the high mutagenic potential of the 8-hydroxyguanine (8-oxodG) along the DNA. Aim of this study was to characterize the biological effects, in a mammalian cell background, of human MUTYH mutations identified in MAP patients (137insIW [c.411_416dupATGGAT; p.137insIleTrp]; R171W [c.511C>T; p.Arg171Trp]; E466del [c.1395_1397delGGA; p.Glu466del]; Y165C [c.494A>G; p.Tyr165Cys]; and G382D [c.1145G>A; p.Gly382Asp]). We set up a novel assay in which the human proteins were expressed in Mutyh,/, mouse defective cells. Several parameters, including accumulation of 8-oxodG in the genome and hypersensitivity to oxidative stress, were then used to evaluate the consequences of MUTYH expression. Human proteins were also obtained from Escherichia coli and their glycosylase activity was tested in vitro. The cell-based analysis demonstrated that all MUTYH variants we investigated were dysfunctional in Base Excision Repair. In vitro data complemented the in vivo observations, with the exception of the G382D mutant, which showed a glycosylase activity very similar to the wild-type protein. Our cell-based assay can provide useful information on the significance of MUTYH variants, improving molecular diagnosis and genetic counseling in families with mutations of uncertain pathogenicity. Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] Surveillance for endometrial cancer in hereditary nonpolyposis colorectal cancer syndromeINTERNATIONAL JOURNAL OF CANCER, Issue 4 2007Laura Renkonen-Sinisalo Abstract The estimated lifetime risk for endometrial carcinoma (EC) in hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is 32,60%, thus supporting surveillance. The survival rate of EC patients is, however, favourable questioning the need for surveillance. Yet, the effectiveness of gynecological surveillance remains to be shown. The 2 previously published studies were based on transvaginal ultrasound (TVUS) alone. Intrauterine biopsy has not been tested in surveillance for EC in HNPCC families. The effect of gynecological surveillance was evaluated among 175 Finnish mutation carriers. During 759 person years at risk, there were 503 surveillance visits including TVUS and intrauterine biopsy of endometrium at 94% and 74% of the visits, respectively. EC occurred in 14 cases, 11 of which were diagnosed by surveillance, 8 by intrauterine biopsies. TVUS indicated only 4 EC patients but missed 6 other cases. Intrauterine sampling detected 14 additional cases of potentially premalignant hyperplasia. The stage distribution and survival tended to be more favorable in the 14 EC cases of the surveilled group (no deaths) than in the group of 83 symptomatic mutation carriers of whom 6 died of EC, but with no statistical significance. Four cases of ovarian cancer occurred but none was detected by surveillance in TVUS examinations. In conclusion, EC surveillance in HNPCC seems more effective with endometrial biopsies than with TVUS alone. A definite improvement in survival remains to be shown. The detection of early cancer stages and premalignant lesions offers the opportunity to avoid extensive adjuvant treatment. © 2006 Wiley-Liss, Inc. [source] Colorectal carcinoma in young adults: a retrospective study on Indian patients: 2000,2008COLORECTAL DISEASE, Issue 10Online 2010S. Gupta Abstract Aim, To highlight an increased incidence of colorectal cancer (CRC) amongst young Indian adults. Method, A retrospective study of 305 cases of CRC admitted to SSKM Hospital, Kolkata, India during 2000,2008 was carried out. Results, The ratio (0.64) of under-40 to above-40 CRC patients reported in this study is comparable to those from premier Oncology Centers in India (,0.52) and is higher than those in the Indian National Cancer Registry (,0.20) and international average (0.07). Distinctive tumour characteristics in younger patients including left-sided lesion (69.7%), presentation at an advanced (III/IV) stage (60%), poor histological differentiation (50%) and predominance of mucin-secreting adenocarcinoma (80%) are similar to those reported in the international literature. Some features are suggestive of hereditary non polyposis colorectal cancer syndrome, which may be a possible reason for the high proportion of young CRC patients. Conclusion, A high index of suspicion for CRC among young Indian adults is necessary. [source] | ||||||||||