A two-phase case-control study for colorectal cancer genetic susceptibility: candidate genes from chromosomal regions 9q22 and 3q22.

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer-related death in the Western world. Much of the CRC genetic risk remains unidentified and may be attributable to a large number of common, low-penetrance genetic variants. Genetic linkage studies in CRC families have reported additional association with regions 9q22-31, 3q21-24, 7q31, 11q, 14q and 22q. There are several plausible candidate genes for CRC susceptibility within the aforementioned linkage regions including PTCH1, XPA and TGFBR1 in 9q22-31, and EPHB1 and MRAS in 3q21-q24. METHODS: CRC cases and matched controls were from EPICOLON, a prospective, multicentre, nationwide Spanish initiative, composed of two independent phases. Phase 1 corresponded to 515 CRC cases and 515 controls, whereas phase 2 consisted of 901 CRC cases and 909 controls. Genotyping was performed for 172 single-nucleotide polymorphisms (SNPs) in 84 genes located within regions 9q22-31 and 3q21-q24. RESULTS: None of the 172 SNPs analysed in our study could be formally associated with CRC risk. However, rs1444601 (TOPBP1) and rs13088006 (CDV3) in region 3q22 showed interesting results and may have an effect on CRC risk. CONCLUSIONS: TOPBP1 and CDV3 genetic variants on region 3q22 may modulate CRC risk. Further validation and meta-analysis should be undertaken in larger CRC cohorts.

Severe complications limit long-term clinical success of self-expanding metal stents in patients with obstructive colorectal cancer.

OBJECTIVES: Self-expanding metal stents (SEMS) are increasingly being used to treat malignant colorectal obstruction. However, complications have been reported in up to 50% of patients. There is limited information on long-term outcomes of these patients. The aim of this study was to retrospectively assess the long-term clinical success of SEMS in patients with malignant colorectal obstruction in a single tertiary center and to identify possible predictive factors of developing complications. METHODS: A total of 47 attempts to insert colorectal SEMS were made in 47 patients during a 5-year period. Stents of 9-cm length were placed under endoscopic and radiologic monitoring. After 24 h, all patients underwent abdominal X-ray to verify correct positioning of the stent. Patients were followed at the outpatient clinic. RESULTS: Insertion success was achieved in 44 (94%) patients. Acceptable initial colonic decompression was observed in 44 out of 47 (94%) attempts and in all (100%) successfully inserted stents. The stents were placed in the rectum (n=7, 15%), sigmoid (n=33, 70%), left colon (n=4, 9%), or anastomosis (n=3, 6%). The majority of patients had stage IV disease (n=40, 85%). SEMS served as a bridge to scheduled surgery in 9 (20%) patients and as a palliative definitive treatment in 38 (80%) cases. Three patients were lost to follow-up, so the outcome was evaluated in 41 patients. Long-term clinical failure occurred in 21 (51%) patients and was due to complications such as: migration (n=9, 22%), obstruction (n=7, 17%), perforation (n=3, 7%), and tenesmus (n=2, 5%). Perforations occurred 3, 4, and 34 days after insertion, and all patients died. In the bridge-to-surgery group, primary anastomosis was possible in only four of nine patients (44%). Clinical failure was not associated with any tumor-related factor. However, eight of nine patients with stent migration and two of three patients with perforation had been previously treated with chemotherapy. CONCLUSIONS: Placement of SEMS does not seem to be as effective as suggested because of late complications. For patients with potentially curable lesions, the use of colonic stents for malignant obstruction should only be considered when surgery is scheduled shortly after the stent insertion. Moreover, in patients with incurable obstructing colorectal cancer eligible for chemotherapy and a long life expectancy, palliative treatments other than SEMS should be considered.