Attitudes Towards Prophylactic Colectomy in Hereditary Non-polyposis Colorectal Cancer (HNPCC) Patients
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2048185 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Among women with HNPCC, this study will assess:
1. Knowledge of screening recommendations for endometrial and ovarian cancers.
2. Perceived risk and cancer worries regarding endometrial, ovarian and colorectal cancers.
3. Adherence to screening recommendations for endometrial, ovarian and colon cancers.
4. Perceived benefits,supports and barriers to endometrial and ovarian cancer screening.
5. Patterns of communication about endometrial and ovarian cancer risk within families with HNPCC and with health care providers.
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Project description:The purpose of this study was to identify novel colorectal cancer (CRC)-causing alleles in unexplained familial CRC cases. In order to do so, coding regions in five candidate genes (MGMT, AXIN2, CTNNB1, TGFBR1 and TGFBR2) were sequenced in 11 unrelated microsatellite-stable hereditary non-polyposis CRC (MSS HNPCC) cases. Selected genetic variants were genotyped in a discovery set of 27 MSS HNPCC cases and 85 controls. One genetic variant, rs67687202, in TGFBR1 emerged as significant (P = 0.002), and it was genotyped in a replication set of 87 additional MSS HNPCC-like cases and 338 controls where it was also significantly associated with MSS HNPCC cases (P = 0.041). In the combined genotype data, rs67687202 was associated with a moderate increase in CRC risk (OR = 1.68; 95% CI = 1.13-2.50; P = 0.010). We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is a CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk.
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Project description:Background and study aims Prophylactic surgery of familial adenomatous polyposis (FAP) includes total colectomy with ileorectal anastomosis (IRA) to proctocolectomy with ileoanal anastomosis (IAA). Surgical guidelines rely on studies without systematic endoscopic follow-up and treatment. Our aim was to report our experience based on a different approach: therapeutic follow-up, comparing in this setting IRA and IAA in terms of oncological safety and quality of life. Patients and methods Between January 1965 and November 2015, all patients who underwent prophylactic surgery for FAP with therapeutic endoscopic follow-up in Lyon University hospital: systematic endoscopic treatment of adenomas, were retrospectively and prospectively (since 2011) included. Results A total of 296 patients were analyzed: 92 had proctocolectomy with IAA (31.1 %), 197 total colectomy with IRA (66.5 %), and seven abdominoperineal resections (2.4 %). Median follow-up was 17.1 years (range, 0-38.1). Incidence of secondary cancer (IR vs. IAA) was 6.1 % vs. 1.1 % ( P = 0.06; 95 %CI 0.001-0.36). The 15-year cancer-free and overall survival (IR vs. IAA) were 99.5 % vs 100 % ( P = 0.09) and 98.9 % vs. 98.8 % ( P = 0.82), respectively. Postoperative morbidity occurred in 44 patients: 29 (14.7 %) in the IRA and 15 (16.3 %) in the IAA group ( P = 0.72). The mean number of stools per day in the respective groups were 4.4 (2.5) vs. 5.5 (2.6) ( P = 0.001). Fecal incontinence occurred in 14 patients (7.1 %) in the IRA vs. 16 (17.4 %) in the IAA group ( P = 0.03). Conclusions A combination of therapeutic endoscopic treatment and extended rectal preservation appears to be a safe alternative to ileoanal J-pouch anastomosis.
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