Association of IVS10+12G>A polymorphism in hMSH2 gene with colorectal cancer in Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the single-nucleotide polymorphism (SNP) IVS10+12 G>A in hMSH2 gene with colorectal cancer in a Chinese population of Jiangsu province.</p><p><b>METHODS</b>A case-control study to investigate whether this SNP affects the risk of developing colorectal cancer was conducted. Subjects included 108 colorectal cancer patients and 180 healthy individuals. Peripheral white blood cell DNA was obtained from all subjects. The hMSH2 gene IVS10+12 G>A was genotyped using a PCR-based DHPLC, the existence of IVS10+12 G>A was verified by DNA sequencing.</p><p><b>RESULTS</b>The allele frequency of the IVS10+12 G>A in the hMSH2 gene in the healthy individuals was 51.7%. There was significant difference in the frequency of the IVS10+12 G>A between patients and healthy controls (P<0.05), and between familial patients and healthy controls (P<0.05). There was also significant difference of the frequency of the IVS10+12 G>A between patients younger than 50 years, and patients with high consumption of fried food and pickled vegetable and healthy controls respectively (P<0.05).</p><p><b>CONCLUSION</b>This SNP may be associated with colorectal cancers in Chinese. Further investigation with larger sample size is needed.</p>

Mismatch repair gene hMLH1 A655G/A polymorphism and colorectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the etiological role of hMLH1 gene A655 polymorphism in colorectal cancer.</p><p><b>METHODS</b>A case-control study was carried out, including 115 colorectal cancer patients and 135 healthy people as control. Genomic DNA was extracted from peripheral white blood cell from all the subjects. Polymorphism was detected by PCR-based DHPLC analysis and verified by DNA sequencing.</p><p><b>RESULTS</b>The hMLH1 gene A655G polymorphism was detected in 3.0% of healthy people and 11.3% of colorectal cancer patients (P<0.01), and the difference was significant (P<0.01). The hMLH1 gene A655G polymorphism was detected in 8.2% of tubular adenocarcinoma or tubular-papillary adenocarcinoma and 27.8% of mucinous adenocarcinoma, which was also significant (P<0.05).Meanwhile, hMLH1 gene A655G polymorphism was not associated with age, gender and lymphatic metastasis (all P>0.05).</p><p><b>CONCLUSIONS</b>The hMLH1 gene A655G polymorphism may play a role in the pathogenesis of colorectal cancer. Determination of the polymorphism may be a potential marker to predict the prognosis of colorectal cancer patients.</p>

Transsacral local wide resection for mid-lower rectal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of transsacral local wide resection for mid-lower rectal tumors.</p><p><b>METHODS</b>Clinical data of 133 patients undergone transsacral local wide resection for mid-lower rectal tumors between September 1994 and September 2005 were analyzed retrospectively.</p><p><b>RESULTS</b>No patient died during operation. Fecal fistula occurred in 6(4.5%) patients. Negative resection margin was proved histologically in all the patients. Postoperative diagnosis was adenoma in 28 patients, hyperplastic polyp in 3 patients, carcinoid in 8 patients, gastrointestinal stromal tumor in 1 patient,adenoma with intra-mucosal carcinogenesis in 29 patients and adenocarcinoma invading into submucosa in 64 patients. Median follow-up was 76 months in 64 patients with T(1) adenocarcinoma, whose 5-year cumulative local recurrence and overall survival were 2.0% and 100% respectively. No local recurrence was observed in other patients.</p><p><b>CONCLUSION</b>Transsacral local wide resection is simple and safe for mid-lower rectal tumors, which is an appropriate procedure for mid-lower rectal benign tumor and can serve as a sphincter-saving operation for selected T(1) lower rectal carcinoma.</p>

Genetic polymorphisms of alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 associated with the susceptibility on esophageal cancer / 中华流行病学杂志

Objective To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on the susceptibility of esophageal cancer. Methods A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high -- performance liquid chromatography (DHPLC). Results (1) Compared with ALDH2 G/G carriers, ALDH2 A/A (OR=5.69, 95%CI: 2.51-12.18) and ALDH2 G/A (OR=1.70, 95%CI: 1.08-2.68) carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 A/A (OR=8.63,95% CI: 2.07-35.95). (2) Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. (3) Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. (4)Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A , drinkers with ALDH2 G/A or A/A and ADH2 C,/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer (OR=8.36, 95% CI: 2.98-23.46). Conclusion These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.

Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the status of hypermethylation in the promoter 1A region of the adenomatus polyposis coli (APC) gene in 3 familial adenomatous polyposis (FAP) pedigrees and to screen large fragment deletions in the APC gene.</p><p><b>METHODS</b>DNA from tumor tissues and corresponding normal tissues of 5 FAP patients was modified by sodium bisulfite. Then the methylation status of the APC gene was analyzed by methylation specific-PCR (MSP) and DNA sequencing. Multiplex ligation-dependent probe amplification (MLPA) was used to screen aberrations involving large fragments from all the 15 exons and promoter region of APC gene.</p><p><b>RESULTS</b>No methylation was present in normal tissues. Hypermethylation was found in tumor tissues of one proband and her son. Loss of heterozygosity was observed in another patient from the same FAP family.</p><p><b>CONCLUSION</b>Aberrant methylation of the APC promoter region provides an important mechanism for impairing APC function and may occur early during colon neoplasia progression. Loss of heterozygosity may play a role in patients with classical polyposis.</p>

The expression of mutation p53 gene from circulating cancer cells of peripheral blood and the clinical significance in detecting the patients with colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the clinical significance of detecting p53 gene mutation expression in colorectal cancer cells of peripheral blood.</p><p><b>METHODS</b>Flow cytometry (FCM) was used to detect p53 gene mutation expression in peripheral blood cancer cells of 128 patients with colorectal cancer. Experimental data were analyzed by SPSS (v.11.0) software.</p><p><b>RESULTS</b>The lymph node metastasis showed the significant difference statistically (P<0.01) between p53 positive and negative expression in the colorectal cancer patients. The mutation p53 expression associated with existing histological differentiation (r=0.8476, P<0.05). A lymph node metastasis difference was observed between left and right colorectal cancers of mutation p53 positive expression.</p><p><b>CONCLUSION</b>Detecting the mutation p53 expression in cancer cells of peripheral blood might be helpful to the early diagnosis of colorectal cancer.</p>

A novel APC gene germline mutation in a familial adenomatous polyposis pedigree / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the adenomatous polyposis coli (APC) gene germline mutation in the proband and her family members with familial adenomatous polyposis (FAP).</p><p><b>METHODS</b>The diagnosis of a patient with FAP was validated by colonoscopy, pathology and the family history. The systematic screening with multiplex ligation-dependent probe amplification (MLPA), denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing were carried out to detect APC gene germline mutations.</p><p><b>RESULTS</b>A novel mutation c.1999 C >T (Q667X) of APC, which leads to premature termination of the protein, was identified in this family. This mutation manifested an aggressive form of FAP with early onset of colorectal adenocarcinoma and colonic adenoma.</p><p><b>CONCLUSION</b>The mutation of APC Q667X is the cause of clinical phenotype of this family with FAP, and the prophylactic colectomy for the affected family members should be considered.</p>

Study of in vivo micronucleus formation in lymphocytes from the patients and its relation to malignant degrees of colorectal cancer / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of the micronucleus (MN) formation in lymphocytes from patients with the malignant degrees of colorectal cancer.</p><p><b>METHODS</b>The MN test in capillary blood lymphocytes was conducted in 112 patients randomly selected from in-hospital patients before therapy. Experimental data were analyzed by SPSS (v.10.1) software.</p><p><b>RESULTS</b>The differences in the frequency of MN between 7 pathological types of colorectal cancers and controls were statistically significant (P<0.01). The frequency of MN increased with the decrease of the histological differentiation in colorectal cancer, and the statistically significant differences were seen between low differentiation group and the other differentiation groups in colorectal cancers.</p><p><b>CONCLUSION</b>There is a significant correlation between MN formation and the malignant degrees of colorectal cancer, and MN formation will be a useful biomarker for the identification of malignant degrees of colorectal cancer before operation or for the screening of high risk subgroup.</p>