Cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations.

PURPOSE: Studies investigating the association between genetic polymorphism of cyclin D1 (CCND1) G870A and risk of colorectal cancer (CRC) reported conflicting results. In order to derive a more precise estimation of the relationship, a meta-analysis was performed. MATERIALS AND METHODS: We performed an extensive search of relevant studies and carried out a meta-analysis, including 20 studies with 5,975 cases and 8,333 controls, to obtain a more precise estimate. RESULTS: Overall, significantly elevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs. GG: OR = 1.23, 95% CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95% CI = 1.01-1.26; dominant model: OR = 1.16, 95% CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected among Caucasians (AA vs. GG: OR = 1.27, 95% CI = 1.04-1.44; dominant model: OR = 1.17, 95% CI = 1.02-1.34).We also observed sporadic CRC with an increased cancer susceptibility (AA vs. GG: OR = 1.24, 95% CI = 1.04-1.48; dominant model: OR = 1.17, 95% CI = 1.04-1.33), when colorectal cancer was stratified into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC). However, no significant associations were found in both Asians and HNPCC patients for all genetic models. CONCLUSION: Result suggests that the cyclin D1 870A allele is a low-penetrant risk factor for developing sporadic colorectal cancer, especially among Caucasians.

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population.

To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption and the susceptibility to esophageal cancer in a Chinese population, we conducted a case-control study with 221 cases and 191 population-based controls in the Taixing city of Jiangsu Province of China. ADH2 and ALDH2 genotypes were examined using PCR and denaturing high-performance liquid chromatography. Alcohol drinkers with the ALDH2 A allele showed a significantly increased risk of esophageal cancer compared with drinkers with the ALDH2 G/G genotype (odds ratio (OR)=3.08, 95% confidence interval (CI): 1.65-5.78) or nondrinkers with any genotype (OR=3.05, 95% CI: 1.49-6.25). Drinkers with the ALDH2 A allele and a cumulative amount of alcohol consumption > or =2.5 (kg * years) were at a significantly higher risk of developing esophageal cancer (OR=11.93, 95% CI: 3.17-44.90) compared with individuals with ALDH2 G/G genotypes and a cumulative amount of alcohol consumption <2.5 (kg * years). A dose-dependent positive result was found between cumulative amount of alcohol consumption and risk of esophageal cancer in individuals carrying the ALDH2 A allele (P=0.023) and the homozygous ALDH2 G allele (P=0.047). Compared with individuals carrying both ALDH2 G/G and ADH2 A/A alleles and with a cumulative amount of alcohol consumption <2.5 (kg * years), drinkers carrying both ALDH2 A and ADH2 G alleles and with a cumulative amount of alcohol consumption > or =2.5 (kg * years) showed a significantly elevated risk of esophageal cancer (OR=53.15, 95% CI: 4.24-666.84). This result suggests that to help lower their risk for esophageal cancer, persons carrying the ALDH2 A allele should be encouraged to reduce their consumption of alcoholic beverages.

Relationship between growth hormone 1 genetic polymorphism and susceptibility to colorectal cancer.

The aim of this study was to evaluate the relationship between smoking, alcohol drinking and genetic polymorphism of the growth hormone 1 gene (GH1) T1663A with reference to colorectal cancer. We conducted a case-control study with 315 cases of colorectal cancer and 438 population-based controls in the Jiangsu Province, China. GH1 T1663A genotypes were identified using PCR-RFLP (restriction fragment length polymorphism) methods. Information on smoking and drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The distribution of T/T and A/A genotypes was significantly different between controls and cases (chi(2)(MH)=3.877, P=0.049). Compared with the GH1 T/T genotype, the A/A genotype was at a decreased risk of developing colorectal cancer (sex-, age-, body mass index-, smoking- and alcohol drinking-adjusted OR=0.56, 95% confidence interval: 0.34-0.90). Smoking was not associated with the risk of colorectal cancer, whereas alcohol drinking was associated with an increased risk of colorectal cancer. Among nonsmokers or nondrinkers, individuals who had the GH1 A/A genotype were at a decreased risk of developing colorectal cancer compared with individuals who had the GH1 T allele. These results show that the GH1 T1663A A/A genotype can decrease the risk for colorectal cancer.

[Association of IVS10+12G>A polymorphism in hMSH2 gene with colorectal cancer in Chinese].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: This SNP may be associated with colorectal cancers in Chinese. Further investigation with larger sample size is needed.

[Promoter hypermethylation and loss of heterozygosity of the APC gene in patients with familial adenomatous polyposis].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Transabdominal transanal resection of distal rectal cancer after high dose preoperative radiotherapy: a Chinese experience in preserving sphincter function.

BACKGROUND: The combination of high dose preoperative radiotherapy and transanal abdominal transanal radical proctosigmoidectomy and colo-anal anastomosis as a sphincter-preserving method has never been performed in mainland China. OBJECTIVES: To assess the feasibility and efficacy of high dose preoperative radiotherapy and TATA as a sphincter-preserving method in Jiangsu, an economically well-developed region of China with a population of 70 million people. METHODS: From September 1994 to September 2000, 25 consecutive patients with pathologically confirmed distal rectal adenocarcinoma were treated preoperatively with a total dose of 45-46 Gy at 1.8-2.0 Gy per fraction during 5 weeks. Sphincter-preserving surgery by TATA was performed 4-6 weeks after radiotherapy. RESULTS: Acute toxicity of preoperative radiotherapy was tolerable. Eight percent of the patients presented pathologic complete tumor response after preoperative radiotherapy. All patients underwent TATA as scheduled. During a median follow-up of 70 months, the 5 year survival rate was 88%. The 5 year survival rate for those tumors down-staged to pathological TO or to pT1 was 100%. CONCLUSIONS: High dose preoperative radiotherapy and TATA as a sphincter-preserving method was feasible and efficient in Chinese patients with distal rectal cancer. In this study, the subset of patients with a good response to radiotherapy had a better clinical outcome.

[The expression of mutation p53 gene from circulating cancer cells of peripheral blood and the clinical significance in detecting the patients with colorectal cancer].

OBJECTIVE: To study the clinical significance of detecting p53 gene mutation expression in colorectal cancer cells of peripheral blood. METHODS: 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. RESULTS: 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. CONCLUSION: Detecting the mutation p53 expression in cancer cells of peripheral blood might be helpful to the early diagnosis of colorectal cancer.

[A novel APC gene germline mutation in a familial adenomatous polyposis pedigree].

OBJECTIVE: To detect the adenomatous polyposis coli (APC) gene germline mutation in the proband and her family members with familial adenomatous polyposis (FAP). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical Observations on Treatment for Chinese Patients with Gastrointestinal Stromal Tumors.

BACKGROUND: To investigate the diagnostic and treatment methods for Chinese patients with gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: From January 2004 to June 2014, patients diagnosed with primary GIST and treated by a single medical team in the Department of Digestive Disease of XuYi Hospital of Traditional Chinese Medicine were retrospectively recruited. Re-examination and follow-up was conducted regularly and abdominal enhanced CT, blood biochemistry and responses to surgery or imatinib were recorded. RESULTS: A total of 15 patients were enrolled, including 9 male and 6 female patients, with an average age of 54 years (ranging from 32-81 years). The primary symptoms were abdominal uncomfortable in 5 patients, abdominal pain in 6 patients as well as nausea and vomiting in 4 patients. One patient was diagnosed with bowl obstruction at the first visit. All patients were treated with surgery, and tumor site was confirmed 1 esophagus, 6 stomach, 4 small bowel, and 4 colorectal and all patients were pathologically diagnosed with GIST. Immunochemical test positive for CD 117 was found 12 patients, and positive for CD 34 in7 patients. The median follow-up time was 24 months (range of 3-63). Three metastasis were confirmed 1.5, 2 and 2.6 years postoperatively. Three patients were treatment by imatinib postoperatively. CONCLUSIONS: Surgery remains the main treatment method for Chinese patients with GIST and imatinib could be feasible and safe for treating Chinese patients with GIST.

Carcinoma microsatellite instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for stage II rectal cancer.

PURPOSE: Rectal cancers with high microsatellite-instable have clinical and pathological features that differentiate them from microsatellite-stable or low- frequency carcinomas, which was studied rarely in stage II rectal cancer, promoting the present investigation of the usefulness of microsatellite-instability status as a predictor of the benefit of adjuvant chemotherapy with fluorouracil in stage II rectal cancer. PATIENTS AND METHODS: Data of 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2008 to 2012 were retrospectively collected. All patients experienced a total mesorectal excision (TME) operation. Survival analysis were analyzed using the Cox regression method. RESULTS: Five-year rate of disease-free survival (DFS) was noted in 390 (84.8%) of 460 patients with stage II rectal cancer. Of 460 tissue specimens, 97 (21.1%) exhibited high-frequency microsatellite instability. Median age of the patients was 65 (50-71) and 185 (40.2%) were male. After univariate and multivariate analysis, microsatellite instability (p= 0.001), female sex (p< 0.05) and fluorouracil-based adjuvant chemotherapy (p< 0.001), the 3 factors were attributed to a favorable survival status independently. Among 201 patients who did not receive adjuvant chemotherapy, those cancers displaying high-frequency microsatellite instability had a better 5-year rate of DFS than tumors exhibiting microsatellite stability or low-frequency instability (HR, 13.61 [95% CI, 1.88 to 99.28]; p= 0.010), while in 259 patients who received adjuvant chemotherapy, there was no DFS difference between the two groups (p= 0.145). Furthermore, patients exhibiting microsatellite stability or low-frequency instability who received adjuvant chemotherapy had a better 5-year rate of DFS than patients did not (HR, 5.16 [95% CI, 2.90 to 9.18]; p< 0.001), while patients exhibiting high-frequency microsatellite instability were not connected with increased DFS (p= 0.696). It was implied that female patients had better survival than male. CONCLUSION: Survival status after anterior resection of rectal carcinoma is related to the microsatellite instability status, adjuvant chemotherapy and gender. Fluorouracil-based adjuvant chemotherapy benefits patients of stage II rectal cancer with microsatellite-stable or low microsatellite-instable, but not those with high microsatellite- instable. Additionally, free of adjuvant chemotherapy, carcinomas with high microsatellite-instable have a better 5-year rate of DFS than those with microsatellite-stable or low microsatellite-instable, and female patients have a better survival as well.

Analysis of Small Fragment Deletions of the APC gene in Chinese Patients with Familial Adenomatous Polyposis, a Precancerous Condition.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly caused by mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectal polyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-year old if total proctocolectomy is not performed. So identification of APC germline mutations has great implications for genetic counseling and management of FAP patients. In this study, we screened APC germline mutations in Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristics of Chinese FAP patients. MATERIALS AND METHODS: The FAP patients were diagnosed by clinical manifestations, family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards, genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerase chain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification (MLPA) for large duplications and/or deletions. RESULTS: We found 6 micromutations out of 14 FAP pedigrees, while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p. Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13), c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and all deletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA and two c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in the CAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5'-CCTGAACA-3' ,3'-ACAAGTCC-5 palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon 1309. CONCLUSIONS: Though there were no novel mutations found as the pathogenic gene of FAP in this study, we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especially the 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene.

Genomic structure of the human beta-PIX gene and its alteration in gastric cancer.

beta-PIX, a newly identified p21-activated kinase (PAK)-interacting exchange factors (PIX), encodes a guanine nucleotide exchange factor for Rho guanosine triphosphatases. Characterization of beta-PIX gene was performed using the BAC Library method. The beta-PIX gene has 17 exons and an A/T polymorphism at the 32nd base upstream of the intron/exon junction of exon 7. The frequencies of genotypes A/T, A/A and T/T were 23.6% (13/55), 72.7% (40/55) and 3.6% (2/55), respectively; these frequencies are in Hardy-Weinberg equilibrium. Two out of 14 informative tumors (14.3%) were shown to have lost their heterozygosity at this locus, but no mutations in the remaining alleles were detected. In addition, we examined the gene-expression profile in another set of 30 gastric samples, but no significant over-expression of either the beta-PIX gene or the alpha-PIX gene was found. Though the beta-PIX gene has been speculated to potentially have tumor-related biological characteristics, the findings of the present study suggest that the involvement of beta-PIX gene in human gastric carcinogenesis is minimal.

[Study of in vivo micronucleus formation in lymphocytes from the patients and its relation to malignant degrees of colorectal cancer].

OBJECTIVE: To investigate the association of the micronucleus (MN) formation in lymphocytes from patients with the malignant degrees of colorectal cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Mutation analysis on MSH2 and MLH1 genes in patients of colorectal cancer at early age].

OBJECTIVE: To investigate the etiological role of function and construction alteration in mismatch repair genes MSH2 and MLH1 in the patients onset of colorectal cancers (CRC) at early ages. METHODS: The genomic DNA was extracted from the tumor tissues and normal colon tissues during operation and subjected to analysis of microsatellite instability (MSI) in 42 Chinese patients aged less than 50 with CRC. Mutation screenings were performed with denaturing high-performance liquid chromatography (DHPLC) followed by DNA sequencing of DNA samples with variant peaks, and genomic deletion detection with quantitative multiplex PCR (Q-M-PCR) in the patients uncovered with MSI(+). RESULTS: 22 out of the 42 (52.4%) patients investigated were microsatellite instability positive (MSI(+)), 10/42 MSI(+)-H and 12/42 MSI(+)-L. 8 kinds of DNA germline alterations, 5 polymorphisms and 3 novel point mutations, were found in 9 patients with MSI(+). A large DNA (exon 1-6) deletion in MSH2 gene and a missense mutation Met242Ile in MLH1 gene were unveiled in CRC tissues of two patients with MSI(+)-H. CONCLUSION: Mutations of mismatch repair genes are frequent in Chinese patients of CRC with onset at early ages.

Outcomes based on risk assessment of anastomotic leakage after rectal cancer surgery.

PURPOSE: Anastomotic leakage (AL) is associated with high morbidity and mortality, high reoperation rates, and increased hospital length of stay. Here we investigated the risk factors for AL after anterior resection for rectal cancer with a double stapling technique. PATIENTS AND METHODS: Data for 460 patients who underwent primary anterior resection with a double stapling technique for rectal carcinoma at a single institution from 2003 to 2007 were prospectively collected. All patients experienced a total mesorectal excision (TME) operation. Clinical AL was defined as the presence of leakage signs and confirmed by diagnostic work-up according to ICD-9 codes 997.4, 567.22 (abdominopelvic abscess), and 569.81 (fistula of the intestine). Univariate and logistic regression analyses of 20 variables were undertaken to determine risk factors for AL. Survival was analysed using the Cox regression method. RESULTS: AL was noted in 35 (7.6%) of 460 patients with rectal cancer. Median age of the patients was 65 (50-74) and 161 (35%) were male. The diagnosis of AL was made between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate and multivariate analysis, age (p=0.004), gender (p=0.007), tumor site (p<0.001), preoperative body mass index (BMI) (p<0.001), the reduction of TSGF on 5th POD less than 10U/ml (p=0.044) and the pH value of pelvic dranage less than or equal to 6.978 on 3rd POD (p<0.001) were selected as 6 independent risk factors for AL. It was shown that significant differences in survival of the patients were AL-related (p<0.001), high ASA score related (p=0.036), high-level BMI related (p=0.007) and advanced TNM stage related (p<0.001). CONCLUSIONS: AL after anterior resection for rectal carcinoma is related to advanced age, low tumor site, male sex, high preoperative BMI, low pH value of pelvic drainage on POD 3 and a significant reduction of TSGF on POD 5. In addition to their high risk of immediate postoperative morbidity and mortality, AL, worse physical status, severe obesity and advanced TNM stage have similarly negative impact on survival.

Risk assessment on anastomotic leakage after rectal cancer surgery: an analysis of 753 patients.

PURPOSE: To investigate the risk factors for anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. PATIENTS AND METHODS: Between January 2004 and December 2011, 753 consecutive patients in Jiangsu Cancer Hospital and Research Institute diagnosed with rectal cancer and undergoing anterior resection with a double stapling technique were recruited. All patients experienced a total mesorectal excision (TME) operation. Additionally, decrease of postoperative tumor supplied group of factors (TSGF), which have not been reported before, was proposed as a new indicator for AL. Univariate and multivariate analysis were performed to determine risk factors for AL. RESULTS: AL was detected in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of anastomotic leakage was confirmed between the 6th and 12th postoperative day (POD; mean 8th POD). After univariate analysis and multivariate analysis, age (p<0.001), gender (p=0.002), level of anastomosis (p <0.001), preoperative body mass index (BMI) (p = 0.001) and reduction of TSGF in 5th POD was less than 10 µ/ml (p <0.001) were selected as 5 independent risk factors for AL. It was also indicated that a temporary defunctioning transverse ileostomy (p = 0.04) would decrease the occurrence of AL. CONCLUSION: AL after anterior resection for rectal carcinoma is related to elderly status, low level site of the tumor (below the peritoneal reflection), being male, preoperative BMI and the decrease of TSGF in 5th POD is less than 10 m/ml. Preventive ileostomy is advisable after TME for low rectal tumors to prevent AL.

Acidic pelvic drainage as a predictive factor for anastomotic leakage after surgery for patients with rectal cancer.

PURPOSE: To demonstrate the value of sequential determinations of pelvic drainage in the identification of increased risk of anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. PATIENTS AND METHODS: Between January 2004 and December 2011, data for the daily postoperative pH of pelvic drainage fluid in 753 consecutive patients with rectal cancer who initially underwent anterior resection with a double stapling technique were reviewed. All patients experienced a total mesorectal excision. Patients with anastomotic leakage (Group AL, n=57) were compared to patients without leakage (Group nAL, n=696). Patients with perioperatively abdominopelvic implants that were likely to affect pH value (determined at 25 °) other than leakage were excluded. Mean postoperative values were compared. RESULTS: Anastomotic leakage was noted in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of anastomotic leakage was made between the 6th and 12th postoperative day (POD; mean 8th POD). There was no significance of the daily average values of pH on POD1 and 2 in group AL while a significantly sharp declining mean pH value reached its diagnostic point of AL (p<0.001) on POD3. A cut-off value of 6.978 on the 3rd POD maximized the sensitivity (98.7.0%) and specificity (94.7%) in assessing the risk of leakage. CONCLUSION: According to these results, an early and persistent declining of pH value of pelvic drainage fluid after rectal surgery with anastomosis, is a marker of AL. A cut-off value of 6.798 on POD3 maximizes sensitivity and specificity.

Role of MYH polymorphisms in sporadic colorectal cancer in China: a case-control, population-based study.

PURPOSE: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic G:C?T:A transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. PATIENTS AND METHODS: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. RESULTS: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 G?A, exon 1-292 G?A and intron 1+11 C?T, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 A?G, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 C?T, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 T?A), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot- spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 A?G (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. CONCLUSIONS: According to these results, the linked variant in Exon 1 region, Intron 10-2 A?G of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

Comparative study on the value of anal preserving surgery for aged people with low rectal carcinoma in Jiangsu, China.

OBJECTIVE: To compare the efficacy of anal preserving surgery for aged people with low rectal carcinoma. METHODS: Clinical data for a consecutive cohort of 98 rectal cancer patients with distal tumors located within 3 cm-7 cm of the anal verge were collected. Among these, 42 received anal preserving surgery (35 with Dixon, 3 with Parks and 4 with transanal operations). The local recurrence and survival rates in the above operations were compared with those of the Miles operation in another 56 patients with rectal cancer. RESULTS: The local recurrence and 3-, 5-year survival rates of anal preserving surgery were 16.7%, 64.3% and 52.4%, those of Miles operations were 16.1%, 67.9% and 51.8% respectively (P>0.05). CONCLUSION: Anal preserving surgery for aged people with low rectal cancer is not inferior to conventional operations in China, with satisfactory long term survival and comparable local recurrence rates.