[Evaluation of optimized sequential screening program of colorectal cancer in current China].

OBJECTIVE: To evaluate the sensitivity and specificity of optimized sequential screening program of colorectal cancer, and provide evidence for the further optimization of colorectal cancer screening program. METHODS: Using cluster sampling method, 4 administrative villages were selected from Jiashan county as a census district in 2011 to 2013. Volunteers of 40 to 74 years old in the census were recruited, and tested by both optimized sequential screening (including questionnaire survey and fecal occult blood test) and colonoscopy for colorectal cancer. Sensitivity and specificity of different screening methods were calculated, respectively. RESULTS: A total of 2 607 volunteers took both simultaneously screening and colonoscopy at the same time. 20 colorectal cancer cases, 85 advanced adenoma cases, 271 non-advanced adenomas cases, and 141 non-adenomatous polyps cases were detected. Sensitivity of optimized sequential screening for colorectal cancer, advanced adenomas, and non-advanced adenomas were 70.0% (14/20) , 57.6% (49/85) and 36.5% (99/271) , specificity was 68.7% (1 776/2 587) , 69.2% (1 746/2 522) and 68.9% (1 610/2 336) , respectively. Sensitivity of the fecal occult blood test of colorectal cancer, advanced adenomas and non-advanced adenomas were 70.0% (14/20) , 47.1% (40/85) and 26.6% (72/271), specificity was 79.4% (2 053/2 587), 79.9% (2 014/2 522) and 79.6% (1 860/2 336). The sensitivity of fecal occult blood test and those of optimized sequential screening for colorectal cancer, advanced adenomas was not significant (χ(2) = 0.00, 1.91, all P values > 0.05). Sensitivity of questionnaire survey of colorectal cancer, advanced adenomas and non-advanced adenomas were 10.0% (2/20), 14.1% (12/85), 12.9% (35/271), specificity was 87.6% (2 266/2 587), 87.7% (2 211/2 522), 87.6% (2 046/2 336). There were no significant difference between non-advanced adenomas. The sensitivity of advanced adenomas and non-advanced adenomas showed no significant decline when the following six term were removed from screening programs: chronic diarrhea, chronic constipation, mucus or bloody history, history of chronic appendicitis or appendectomy surgery, chronic cholecystitis or gallbladder surgery, adverse events in the history of life, while the sensitivity of colorectal cancer remained nearly the same 70.0% (14/20), 52.9% (45/85), 31.4% (85/271) (χ(2) = 0.38, 1.61, all P values > 0.05). CONCLUSION: Current optimized sequential screening programs for colorectal cancer in China have a high sensitivity and specificity. However, further optimization is viable and necessary.

[Association between H-ras and L-myc gene polymorphisms and susceptibility to colorectal cancer].

OBJECTIVE: To explore the association between the polymorphisms of oncogenes H-ras and L-myc and colorectal cancer risk, and the interaction of those genes. METHODS: The genotypes of H-ras and L-myc genes were determined by polymerase chain reaction-based restriction fragment length polymorphism analysis. Stratified analysis and logistic model were used to detect the gene-gene interaction. The gene-gene interaction was validated by multifactor dimensionality reduction (MDR) analysis. RESULTS: The single SNP model showed that the polymorphisms of H-ras and L-myc genes were not significantly related with colorectal cancer risk (P > 0.05). Stratified analysis revealed that among the L-myc LS + SS genotype carriers, those with H-ras TC + CC genotype showed significantly increased risk of rectal cancer than those with TT genotype (OR = 1.81, P = 0.005). The positive interaction between L-myc and H-ras was detected by logistic regression model. The OR of the interaction effect was 2.74 (P = 0.024). This result was confirmed in the MDR model, with 54.83% testing balanced accuracy and 10/10 cross-validation consistency, and the model was still significant after the 1000 times permutation test (P = 0.001). CONCLUSION: Our findings suggest that the polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer.

Performance of a colorectal cancer screening protocol in an economically and medically underserved population.

The performance of combining fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) in colorectal cancer (CRC) screening in economically and medically underserved populations is uncertain. This study investigated the performance of a CRC screening protocol of combining FITs and an HRFQ as primary screening methods in a rural Chinese population. A CRC mass screening was conducted using FITs and an HRFQ as the first and colonoscopy as the second stage of screening in Jiashan, 2007-2009. The target population was 31,963 residents in three communities. The compliance was 84.7% for HRFQ, 76.4% for FITs, and 78.7% for colonoscopy. The detected rates of cancer, adenoma, nonadenomatous polyps, and advanced neoplasm were 2.7%, 14.8%, 5.9%, and 8.9% by FITs, which were higher than those by HRFQ (0.5%, 9.2%, 4.8%, and 3.8%, respectively). There was no significant difference in detected rate for nonadenomatous polyps between FITs and HRFQ. A total of 41.2% adenomas, 53.2% nonadenomatous polyps, and 29.8% advanced neoplasms were detected by HRFQ but missed by FITs. Positive predictive value of the screening protocol of combining FITs and HRFQ for advanced neoplasm was 5.7%, which was higher than FITs alone. Men had a higher prevalence of advanced neoplasm than women. Results indicate that combining FITs and HRFQ as primary screening methods is an efficient CRC screening strategy in economically and medically underserved populations.

[Expression of caspase apoptosis pathway genes mRNA in colorectal cancer and polyps].

OBJECTIVE: To investigate mRNA expression of caspase apoptosis pathway genes in colorectal cancer, polyps and normal mucosa. METHODS: Nineteen patients with colorectal cancer, 86 patients with polyps and 10 normal controls were enrolled from 2008 to 2010. Fluorescence quantitative RT-PCR was performed to detect the mRNA expression of caspase apoptosis pathway genes (caspase-2,-3,-6,-7,-8,-9 and -10) in colorectal cancer, polyps and normal mucosa. RESULT: There were no statistically significant differences of demographic characteristics between patients with colorectal cancer, patients with polyps and normal controls. Compared with normal control group, the mRNA expression of all selected genes except for caspase-3 were lower; however, the P values did not reach statistic significance. Highly positive correlations were observed between mRNA expression of all selected genes except caspase-9. CONCLUSION: There are no significant changes in mRNA expression levels of caspase apoptosis pathway genes from normal mucosa to polyps to cancer. The mRNA expressions of most caspase pathway genes are highly correlated with each other.

[Association of XPC gene polymorphisms with breast cancer risk].

OBJECTIVE: To access the association of xeroderma pigmentosum group C (XPC) Lys939Gln (A/C) and Ala499Val (C/T) polymorphisms with breast cancer risk in a Chinese Han population. METHODS: 173 patients with breast cancer and 171 matched controls in terms of habitation and age (±5 years) were included in this population-based case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was employed to genotyping the Lys939Gln and Ala499Val polymorphisms. Associations of genotypes of Lys939Gln and Ala499Val with breast cancer risk were evaluated using unconditional logistic regression model. Associations between XPC haplotypes and breast cancer risk were estimated by Haplo. Stats package. RESULT: No significant associations were observed both in individual SNPs and haplotype analyses. However, there was a significant interaction between XPC Lys939Gln polymorphism and menopausal status (P=0.032). CONCLUSION: The XPC Lys939Gln polymorphism may modulate breast cancer susceptibility jointly with the menopausal status.

[Association of CASP3 polymorphisms and its haplotypes with susceptibility of breast cancer].

OBJECTIVE: To investigate the association of Caspase3 (CASP3) polymorphisms with susceptibility of breast cancer in Chinese Han population. METHODS: In this population-based case-control study, 251 cases with breast cancers and 251 matched controls in terms of habitation and age (±5 years) were recruited. Rs4647693, rs2696056, rs4647610 were selected as TagSNPs in CASP3 gene and genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The haplotype distribution was estimated and compared by PHASE software. RESULT: There was significant association between menarche age and breast cancer (P=0.007), as well as the early pregnancy age and breast cancer (P=0.002). No significant differences were detected in the distribution of CASP3 genotype and haplotype frequencies between breast cancer patients and controls. The GGA was the most common haplotype both in cases and controls. CONCLUSION: CASP3 polymorphisms and its haplotypes were not related to the susceptibility of breast cancer.

[Optimization of sequential screening scheme in prevention of colorectal neoplasm].

OBJECTIVE: To improve early diagnosis rate and reduce the incidence rate of colorectal cancer, through the application of optimized sequential screening scheme for colorectal neoplasm in general population. METHODS: Quantitative risk assessment by questionnaires survey and fecal occult blood test (FOBT) were used to proceed preliminary screening among people aged 40 to 74. Electronic colonoscopy was applied to examine the whole colon and rectum among identified high-risk subjects. The detected cases received treatment for colorectal cancer, adenomatous polyps or non-adenomatous polyps. The early diagnosis rate and incidence rate of colorectal cancer were evaluated and compared with those before screening. RESULT: With application of optimized sequential screening schemes, various types of colorectal lesions were detected in 1 117 subjects, including 69 cases of colorectal cancer, 701 cases of colorectal adenoma and 211 cases of advanced adenoma. The early diagnosis rate of colorectal cancer was increased by 58.19%, and its incidence rate also decreased significantly. CONCLUSION: The optimized sequential screening scheme is simple, economical, efficient in colorectal cancer screening of general population.

The association of XPC polymorphisms and tea drinking with colorectal cancer risk in a Chinese population.

The xeroderma pigmentosum complementation group C (XPC) is responsible for removal of bulky helix-distorting DNA lesions. Several polymorphisms of XPC gene may modulate the colorectal cancer (CRC) susceptibility. We assessed the association of XPC Lys939Gln (A/C), Ala499Val (C/T), and PAT (-/+) polymorphisms with CRC risk in a population-based case-control study which included 421 CRC patients and 845 controls. For Lys939Gln, the CC genotype was associated with a significantly increased risk of CRC (odds ratio (OR)=1.5; 95% confidence interval (CI)=1.0-2.2) compared with the AA genotype. The subjects with PAT +/+ genotype had a significantly increased risk of CRC (OR=1.5; 95% CI=1.0-2.3), compared with those with PAT-/- genotype. Though no significant association between Ala499Val and CRC risk was observed, we found that individuals carrying the CT+TT genotypes showed a significantly decreased risk of rectal cancer (OR=0.7; 95% CI=0.5-1.0). Additionally, the haplotype C+C was associated with a significantly increased CRC risk (OR=1.3; 95% CI=1.0-1.6), compared with the most common haplotype A-T. Further, individuals with four or more risk alleles exhibited a significantly increased risk of CRC (OR=1.4; 95% CI=1.0-2.0), with a significant gene-dosage effect (P for trend=0.038). Besides, never tea drinking was associated with a significantly increased risk of CRC (OR=2.3; 95% CI=1.7-3.3). Our results suggest that the XPC polymorphisms may modulate CRC susceptibility independently or jointly, and tea drinking has a protective effect on CRC.

Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk.

It has been well elucidated that the signal transduction of cell-cycle control pathway and apoptosis pathway plays an important role in the normal growth and differentiation of organisms. To test the hypothesis that mutants of key genes involved in cell-cycle regulation and apoptosis might contribute to the increased risk of colorectal cancer (CRC), a population-based case-control study was carried out in Jiashan County, Zhejiang Province. The study population was composed of 373 CRC cases and 838 controls. Five genetic variants including CCND1 G870A, p21 codon31 C/A, p21 3'UTR C/T, caspase8 IVS12-19G/A, and caspase8 6n del/ins were genotyped. The associations of the polymorphisms with CRC were estimated by logistical regression model after adjustment for the important covariates. The interactive effect among the five selected genetic polymorphisms on CRC was explored by multifactor dimensionality reduction (MDR) software. The significant association between five single-nucleotide polymorphisms (SNPs) and CRC risk was not observed, respectively. However, caspase8 del/del showed a marginally significant association with the increased risk of rectum cancer [adjusted odds ratio (OR) (95% confidence interval, CI) = 1.92 (0.97-3.79); P = 0.06]. Furthermore, the MDR analysis indicated that the best interactive model for CRC included three factors-CCND1 G870A, caspase8 IVS12-19G/A, and caspase8 6 n del/ins-with 53.44% testing balanced accuracy and 10/10 cross-validation consistency, but the model was no longer significant after the 1000 times permutation test (P = 0.25). Our findings suggest that the selected polymorphisms of p21, CCND1, and caspase8 may not contribute to the risk of colorectal cancer.

[Association between HRE-2 gene polymorphism at codon 655 and genetic susceptibility of colorectal cancer].

OBJECTIVE: To explore the distribution of HER-2 genetic polymorphism at codon 655 and its association with susceptibility of colorectal cancer in Chinese. METHODS: A population-based case-control study was carried out. 292 patients with colorectal cancer and 842 healthy controls were interviewed. Meanwhile, the genetic polymorphism of HRE-2 was detected using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of Ile/Val+Val/Val genotypes and Val allele were both higher in cases (25.34% and 13.36%) than those in controls (18.41% and 9.74%) (P<0.05). Compared with Ile/Ile genotype, Ile/Val+Val/Val genotypes were significantly associated with colorectal cancer [ORadjusted=1.54, 95% CI: 1.11-2.14]. The adjusted odds ratio of interactions between this polymorphism and smoking, alcohol drinking were 1.43 (95%CI: 0.88-2.30) and 1.29 (95%CI: 0.73-2.29), respectively. CONCLUSION: The present findings suggest that HER-2 genetic polymorphism at codon 655 may be associated with the risk of colorectal cancer in Chinese. In addition, there are no interactions between this polymorphism and smoking, alcohol drinking, respectively.

Genetic polymorphisms of transforming growth factor-beta1 and its receptors and colorectal cancer susceptibility: a population-based case-control study in China.

The TGF-beta signaling pathway plays a very important role in the control of cell proliferation and differentiation that is involved in colorectal carcinogenesis. The associations between polymorphisms of TGF-beta1 and its receptors genes and the colorectal cancer risk were assessed in a population-based case-control study (206 cases and 838 controls). We could not observe any variant in the G-800A, codon25 and codon263 of TGF-beta1 and A-364G of TGFbetaR2 in Chinese population. However, the results revealed that -509CT and TT genotypes were significantly associated with decrease risk for colorectal cancer (adjusted OR=0.58, 95% CI 0.40-0.84 and adjusted OR=0.44, 95% CI 0.29-0.68, respectively). Moreover, the linkage disequilibrium analysis revealed that TGF-beta1 C-509T and codon10 polymorphisms were in strong linkage disequilibrium, and the -509C/+29C was associated with a significantly increased risk of colorectal cancer (OR=1.32, 95% CI=1.05-1.66). Our findings indicate that the distributions of polymorphisms in TGF-beta1 and its receptors genes vary greatly among different ethnic groups, and these polymorphisms might contribute to the colorectal cancer susceptibility.

[Application of multifactor dimensionality reduction on the interactions between gene-gene, gene-environment and the risk sporadic colorectal cancer in Chinese population].

OBJECTIVE: To identify the association between risk of sporadic colorectal cancer and the common single nucleotide polymorphisms (SNPs) in DNA repairs genes, gene to gene interactions among them and their gene to environment interactions with common environmental factors. METHODS: In this population-based case-control study, 206 primary colorectal cancer cases and 845 cancer-free healthy controls were enrolled. Genotyping was carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique, with the status of subjects case or controls unknown. Multifactor dimensionality reduction (MDR) and logistic analysis were both used for association analysis. RESULTS: As compared to the younger age group (> or = 42, < 61 years), the risk of colorectal cancer in older age group (> or = 61 years) increased significantly (OR = 2.04, 95% CI: 1.49-2.80). Similar result was observed in the family cancer history (OR = 1.51, 95% CI: 1.05-2.17). However, no significant association between any single DNA repair gene SNP and colorectal cancer risk was discovered. Results from MDR analysis only showed a significant interaction among the four following factors: age, alcohol drinking, XRCC1 Arg194Trp and OGG1 Ser326Cys (the cross-validation consistency = 10/10, the average testing accuracy = 0.616, P = 0.011). Using a logistic regression model, the "high-risk" individuals had a significantly elevated risk of colorectal cancer compared to those "low- risk" individuals classified by the above MDR model (OR = 2.72, 95% CI: 1.66-4.47). CONCLUSION: The impact of polymorphisms in DNA repair genes on the risk of sporadic colorectal cancer exhibited a low-penetrance characteristics while the intricate interactions existing among them and with environmental factors.

Association between H-RAS T81C genetic polymorphism and gastrointestinal cancer risk: a population based case-control study in China.

BACKGROUND: Gastrointestinal cancer, such as gastric, colon and rectal cancer, is a major medical and economic burden worldwide. However, the exact mechanism of gastrointestinal cancer development still remains unclear. RAS genes have been elucidated as major participants in the development and progression of a series of human tumours and the single nucleotide polymorphism at H-RAS cDNA position 81 was demonstrated to contribute to the risks of bladder, oral and thyroid carcinoma. Therefore, we hypothesized that this polymorphisms in H-RAS could influence susceptibility to gastrointestinal cancer as well, and we conducted this study to test the hypothesis in Chinese population. METHODS: A population based case-control study, including 296 cases with gastrointestinal cancer and 448 healthy controls selected from a Chinese population was conducted. H-RAS T81C polymorphism was genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. RESULTS: In the healthy controls, the TT, TC and CC genotypes frequencies of H-RAS T81C polymorphism, were 79.24%, 19.87% and 0.89%, respectively, and the C allele frequency was 10.83%. Compared with TT genotype, the TC genotype was significantly associated with an increased risk of gastric cancer (adjusted OR = 3.67, 95%CI = 2.21-6.08), while the CC genotype showed an increased risk as well (adjusted OR = 3.29, 95%CI = 0.54-19.86), but it was not statistically significant. In contrast, the frequency of TC genotype was not significantly increased in colon cancer and rectal cancer patients. Further analysis was performed by combining TC and CC genotypes compared against TT genotype. As a result, a statistically significant risk with adjusted OR of 3.65 (95%CI, 2.22-6.00) was found in gastric cancer, while no significant association of H-RAS T81C polymorphism with colon cancer and rectal cancer was observed. CONCLUSION: These findings indicate, for the first time, that there is an H-RAS T81C polymorphism existing in Chinese population, and this SNP might be a low penetrance gene predisposition factor for gastric cancer.

[Association of single nucleotide polymorphisms and haplotypes in DNA repair gene XRCC1 with susceptibility of breast cancer].

OBJECTIVE: To examine the contribution of the three most common single nucleotide polymorphisms (SNPs) in XRCC1 gene, C26304T, G27466A and G28152A, to susceptibility of breast cancer in Chinese Han population. METHODS: In this population-based case control study, 84 cases with breast cancer and 252 controls, matched to the cases in terms of habitation and age (5 years), were genotyped for the XRCC1 C26304T, G27466A and G28152A polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The haplotype distribution was estimated and compared by EH linkage software 1. 2. RESULT: The distribution of basic characteristics, such as age, alcohol drinking, the family history of malignancy in first and second relatives except cigarette smoking, were not significantly different between cases and controls. However, the percentage of ever or current smokers was significantly higher in cases (7.1%) than that in controls (2.0%). The distributions of allelotype and genotype of C26304T, G27466A and G28152A polymorphisms were also not significantly different between cases and controls. There was no significant association between the risk of breast cancer and these three SNPs of XRCC1 gene. The genetic linkage disequilibrium existed in these three polymorphic sites both in cases and controls, in which the CGG, CGA, CAG and TGG haplotypes were the most common. There was also no significant association of XRCC1 haplotype with risk of breast cancer. CONCLUSION: XRCC1 C26304T, G27466A and G28152A SNPs may not be associated with the susceptibility of breast cancer. The CGG, CGA, CAG and TGG haplotypes might be the most common haplotypes in Chinese Han population.

Genetic polymorphisms of the uridine diphosphate glucuronosyltransferase 1A7 and colorectal cancer risk in relation to cigarette smoking and alcohol drinking in a Chinese population.

BACKGROUND: The impact of uridine diphosphate glucuronosyltransferase 1A7 (UGT1A7) polymorphisms on genetic susceptibility to digestive system cancer has received close attention since the discovery by Guillemette, the polymorphisms of which may alter enzyme activity. To clarify the allele frequency distribution and its association with risk of colorectal cancer, a population-based case-control study was carried out in Chinese population. METHODS: A total of 140 patients with colorectal cancer and 280 cancer-free frequency-matched controls from a follow-up cohort population established in 1989, were enrolled. For the UGT1A7 polymorphisms analysis, polymerase chain reaction (PCR)-based genotyping techniques including semi-nested PCR, allele-specific PCR and PCR-restriction fragment length polymorphism (RFLP) were developed. RESULTS: The variant allele frequencies in patients and controls were 50.0% and 38.6%, respectively, which were significantly associated with risk of colorectal cancer (odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.19-2.13). For the variant genotypes analysis, *2/*2 and *3/*3 exhibited a significant association with risk of colorectal cancer (OR: 7.80, 95%CI: 2.66-22.87; OR: 3.47, 95%CI: 1.51-7.97, respectively). Stratification analysis indicated that in previous-current cigarette smoking (cigarette smoking history), current cigarette smoking (current cigarette smoking status), previous-current alcohol drinking (alcohol drinking history) or current alcohol drinking individuals (current alcohol drinking status), the risk developing colorectal cancer increased: OR (95%CI), 2.81 (0.97-8.11), 3.39 (1.19-9.67), 2.89 (0.99-8.46) and 3.14 (1.09-9.09), respectively. CONCLUSIONS: UGT1A7 polymorphisms may have a significant modifying effect on colorectal cancer risk, which may interact with environmental factors, cigarette smoking and alcohol drinking in colorectal carcinogenesis.

The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population.

Growing evidence suggests that the Thr241Met (T241M) polymorphism in the homologous recombination repair gene XRCC3 may alter DNA repair capacity and subsequent susceptibility to carcinogens. In a few studies of colorectal cancer (CRC), however, the results have been discrepant. A population-based nested case-control study including 140 cases and 280 cancer-free controls was conducted to evaluate the effect of XRCC3 polymorphism, environmental exposure, and family history (FH) on the risk of CRC. The variant allele frequency was low among the ethnic Han Chinese, but we observed a significant difference between cases (6.07%) and controls (2.32%). The analytic results of the unconditional logistic regression model adjusted by age, sex, alcohol intake, cigarette smoking, and FH of cancer in first-degree relatives showed a significantly increased risk of CRC (adjusted odds ratio [OR] = 3.13, 95% confidence interval [CI]: 1.41-6.95, P = 0.005) as the T/M and M/M genotypes compared with the T/T genotype, which changed weakly in consideration of the subsite (adjusted OR = 4.80, 95%CI: 1.77-12.98, P = 0.002 in colon cancer, adjusted OR = 2.41, 95%CI: 0.93-6.25, P = 0.071 in rectal cancer, respectively). Combined with environmental factors such as alcohol intake and cigarette smoking, no significant interaction could be found. However, the results revealed a significant association between FH of cancer in first-degree relatives and the risk of CRC (adjusted OR = 2.24, 95%CI: 1.18-4.25, P = 0.014). These results also suggest that XRCC3 T241M polymorphism and FH of cancer may be risk factors for CRC, and the XRCC3 241Met allele may be an effective biomarker for genetic susceptibility to CRC. Larger studies are needed to confirm our findings and identify the underlying mechanisms.

The association between drinking water source and colorectal cancer incidence in Jiashan County of China: a prospective cohort study.

BACKGROUND: The pollution of drinking water, e.g. from rivers and pools, has long been recognized to be associated with an increased risk for colorectal cancer (CRC), but there are few direct prospective cohort studies related to person-years on the relative risks of different sources of drinking water for CRC, hence the reason for our study. METHODS: Based on a screening for CRC among residents aged 30 years and over in Jiashan County, Zhejiang Province, China, a total of 64,115 residents were classified into five cohorts by their source of drinking water and followed-up from 1st May 1990 to 1st January 2001. Person-years was calculated for every cohort member and Poisson regression was used to control potential confounding variables including demographic variables and smoking history, and to attain crude and adjusted relative risks based on person-years. RESULTS: A trend was seen toward increasing incidence rates for CRC from the drinking water sources of municipal, river, ditch, mixed water to well in turn as shown by relative risk rates of 29.61, 32.67, 33.45, 40.87 and 58.67 per 100,000 inhabitants. Only the role in risk of well water was significantly different from municipal water (P < 0.05). After the confounding variables were adjusted, the significant risk from well water could be seen for colon cancer, rectal cancer as well as CRC. The relative risks were 1.741 [95% confidence interval (CI) 1.001-3.029], 2.228 (95% CI 1.432-3.466) and 2.022 (95% CI 1.432-2.854), respectively. CONCLUSION: Drinking well water over a long period was identified as playing a role in the risk for CRC, especially for rectal cancer.

Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer.

The aim of this study was to investigate the association of environmental factors (dietary folate, methionine and drinking status) and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) gene, as well as the combination of these factors, with the risk of colon cancer and rectal cancer. A case-control study of 53 colon cancer patients, 73 rectal cancer patients and 343 healthy controls was conducted. Genotypes of C677T and A1298C polymorphisms were analyzed by PCR-RFLP. The dietary folate and methionine intakes were assessed using food-frequency questionnaires and food consumption tables. Unconditional logistic regression was applied to estimate the odds ratios (ORs) and their 95% confidence intervals (CIs). The frequency of MTHFR 677T and 1298C alleles in healthy population were 39.4 and 17.2%, respectively. After adjustment for specific variants, the MTHFR 677TT genotype showed a significantly reduced risk of colon cancer compared with the wild type (OR=0.22, 95% CI: 0.50-0.98), and 1298C allele-carrier showed an inverse association with the risk of rectal cancer compared to the wild type (OR=0.52, 95% CI: 0.28-0.98). Adequate intake of folate was a protective factor from colon cancer (OR=0.32, 95% CI: 0.12-0.88) and MTHFR C677T polymorphism showed a statistically significant effect (OR=0.25, 95% CI: 0.06-0.93), reducing the risk of colon cancer in groups that have an intake of folate exceeding 115.64ng per 1000kcal per day. This study suggests that MTHFR C677T and A1298C polymorphisms are associated with the reduced risk of colon and rectal cancers, respectively. Adequate folate intake shows an inverse association with the risk of colon cancer. There is a significant interaction between MTHFR C677T polymorphism and folate intake in reducing the risk of colon cancer.

Alcohol drinking and colorectal cancer: a population-based prospective cohort study in China.

STUDY OBJECTIVE: To asses the association between alcohol consumption and the risk of colorectal cancer (CRC) in the Chinese population. DESIGN: A population-based prospective cohort study was initiated from the colorectal cancer screening population in Jiashan County in 1989-1990. The drinking habits of individuals were investigated with demographic information. SETTING: A cohort study was followed-up from 1st May 1990 to 1st January 2001 and censored at the date of diagnosis of CRC, at death from any causes, or at 1st January 2001, whichever came first, and the person-time was computed. PARTICIPANTS: Two hundred and forty two CRC patients were diagnosed during the study period and 64,100 individuals finished the follow-up. RESULTS: The distribution of sex, smoking status, occupation, education level and marital status were all significantly different among different drinking habits at baseline. When the above factors were adjusted, no significant association was observed between alcohol consumption and the risk of CRC. Exclusion of individuals diagnosed cancer less than 1 year after the examination date did not alter the strength of an alcohol-CRC relationship. Further analysis in sex strata also did not show a significant relationship. CONCLUSIONS: Alcohol drinking may not be associated with a higher risk of CRC in the Chinese population.

[A case-control study on the association between genetic polymorphisms of metabolic enzymes and the risk of colorectal cancer].

OBJECTIVE: To investigate the association between metabolic enzymes polymorphisms and the risk of colorectal cancer(CRC). METHODS: Methods of detection used were based on polymerase chain reaction(PCR) including PCR-restriction fragment length polymorphism (PCR-RFLP), allele specific-PCR (AS-PCR) and multiple-PCR to identify the polymorphisms of CYP1A1 6235T/C, CYP1A2 734C/A, CYP2E1 -1259G/C, CYP2E1 -1019C/T, GSTM1 and T1 null type, NAT1 and NAT2 alleles among 140 cases and 343 cancer-free controls. RESULTS: The allele frequencies of CYP1A1 6235C, CYP1A2 734A, CYP2E1 -1259C, CYP2E1 -1019T, GSTM1 and T1 null type, NAT1* 10 and NAT2 Mx (x = 1,2,3) alleles were 31.65%, 63.77%, 23.02%, 32.61%, 57.25%, 17.39%, 26.45% and 39.21% in the case group and 39.85%, 66.62%, 20.27%, 28.61%, 55.46%, 20.35%, 25.22% and 39.36% in control group, respectively. The frequencies were in Hardy-Weinberg equilibrium. Data on single genetic polymorphism and stratification analysis of multi-genetic polymorphisms indicated that CYP1A1 6235CC homozygote was associated with the significant reduction of CRC risk (OR = 0.79, 95% CI: 0.63-0.99) and in individuals with CYP1A2 734A allele. CYP1A1 62345C allele had the same effect (OR = 0.53, 95% CI: 0.34-0.83). However, individuals with GSTT1 null genotype, GSTM1 null genotype could significantly increase the risk (OR = 4.41, 95% CI: 1.21-16.10). CONCLUSION: CYP1A1 6235C allele might play an important role in fighting against colorectal carcinogenesis. However, GSTM1 and T1 null genotype might serve as risk factors genetically. Larger scale population-based studies were needed to confirm the current findings.