Genetic Polymorphisms of Vitamin D Receptor Gene are Associated with Cervical Cancer Risk in Northeastern Thailand

Objective: This study aimed to explore whether VDR polymorphisms (Fok1, Apa1 and Taq1) are associated to the cervical cancer in Thai population. Materials and methods: Subjects of 204 cervical cancer patient and 204 age-matched healthy control were enrolled in the case-control study. VDR polymorphisms were detected by using real-time PCR. Haplotype analysis of three loci was applied to the obtained genotypes. Results: Significantly increased risk for cervical cancer was observed in carriers of TT genotype (p = 0.0388) and T allele (p = 0.0357) of Fok1 and TC genotype (p = 0.0001), CC genotype (p = 0.0160) and the C allele of Taq1 (p = 0.0001). Haplotype analyses revealed a significant correlation between C-T-C, T-G-C and T-T-C haplotypes and elevated risk for cervical cancer (OR = 2.06; 95%CI = 1.06-4.00; p = 0.0313, OR = 2.15; 95%CI = 1.22-3.80; p = 0.0078 and OR = 2.81; 95%CI = 1.53-5.16; p = 0.0006, respectively). Furthermore, haplotype carrying C allele of Taq1 (C-G-C + C-T-C + T-G-C + T-T-C) significantly increased cervical cancer risk with OR of 1.92 (95%CI = 1.32-2.79, p = 0.0006). Conclusion: Our finding revealed an association between VDR polymorphisms and cervical cancer risk. Taq1 C allele might be a molecular marker for cervical cancer development.     

Association between Circulating Vitamin D,the Taq1 Vitamin D Receptor Gene Polymorphism and Colorectal Cancer Risk among Jordanians

Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form 1,25(OH)2D to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by pairedt-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancerpatients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT (8.91±4.31) and Tt (9.15±5.25) genotypescompared to control ((21.3±8.31) and (19.3±7.68); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.     

Association of Vitamin D Receptor Gene Polymorphisms with Prostate Cancer Risk in the Pakistani Population

Background: Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic researchrecently. Association studies between different types of cancers including prostate cancer (PCa) and VDR genepolymorphism have also been conducted. The objective of this study was to find possible associations betweenPCa and VDR gene polymorphisms in the Pakistani population. Materials and Methods: A total of 162 subjects,including prostate cancer patients and controls, were genotyped for Apa I, Taq I and Fok I polymorphisms inthe VDR gene using allele specific PCR, PCR-RFLP and direct DNA sequencing. Allelic frequencies were testedfor Hardy-Weinberg equilibrium and associations between the genetic markers and PCa were calculated usinglogistic regression. Results: Apa I CC genotype was found to have strongest association with PCa risk, and “A”genotype was found to have protective effect. Fok I and Taq I did not have appreciable levels of association withPCa, although Taq I “TC” heterozygotes seemed to have some protective effect. Similarly the “C” allele of Fok Ialso seemed to have protective effect. Conclusions: To our knowledge, this is the first report showing associationbetween VDR gene polymorphisms and PCa in Pakistan. Our findings may be somewhat skewed because ofsmall sample size and tendency of consanguineous marriages in Pakistani society; nevertheless, it shows thetrend of association and protective effects of certain VDR gene polymorphisms against PCa.     

MYH基因变异与散发性大肠癌发病风险的初步研究

背景与目的：初步探讨MYH（MutY homologue,MYH）基因的变异与散发性大肠癌发病风险的关系。材料与方法：应用变性高效液相色谱（denaturing high performance liquid chromatography,DHPLC）和测序技术,对140例大肠癌患者及280名正常对照人群的MYH基因16个外显子区域中的7个（外显子1、7、9、11、13、14和16）区域进行变异筛查,用SPSS统计软件进行数据分析。结果：Exon1区域的变异位点为Exonl-316 G〉A、Exonl-292 G〉A和Intronl＋11 C〉T,3者同时出现在所有变异样本中,且病例组变异危险性均为对照组的8．16倍（P=0．04;OR=8．16,95％C／为1．01—203．70）;Exon16区域的变异为nt1678—80delGTF,病例组中直肠癌患者的变异危险性为结肠癌患者的7．18倍（P=0．04;OR=7．18,95％C／为1．102～165）;Exon11区域查出4例Intron10—2A〉G变异;Exon13区域筛查出2例In．on13＋12C〉T变异;Exon14区域筛查出1种错义变异,即Exon14＋74T〉A,P．V463E;Exon7和Exon9区域未筛查出任何变异。结论：MYH变异可能会增加结直肠癌发病风险,应进行监测管理;未筛查到高加索人群中最常见的Exon7区域的变异,提示人种之间变异存在差别。     

Vitamin D Receptor BsmI Polymorphism and Colorectal Cancer Risk: an Updated Analysis

Background: Previous studies have investigated the association between the vitamin D receptor (VDR) BsmI polymorphism and colorectal cancer (CRC) susceptibility, but the results were conflicting. The aim of this study is to quantitatively summarize the relationship between this polymorphism and CRC risk. Materials and Methods: Two investigators independently searched the Medline, Embase, China National Knowledge Infrastructure (CNKI) and Chinese Biomedicine databases for studies published before November 2013. Summary odds ratios (ORs) and 95% confidence intervals (95%CIs) for VDR BsmI polymorphism and CRC were calculated in a fixedeffects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. Results: This meta-analysis included 14 case-control studies, which included 10,822 CRC cases and 11,779 controls. Overall, the variant genotype (BB) of the BsmI was associated with a lower CRC risk when compared with the wild-type bb homozygote (OR=0.66, 95%CI: 0.49-0.88). Similarly, a decreased CRC risk was also found in the dominant and recessive models. When stratifying for ethnicity, source of controls, and study sample size, associations were observed among Caucasians, population-based studies and studies with large study sample size (>1000 subjects). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. No publication bias was found in the present study. Conclusions: This updated meta-analysis suggests that the VDR BsmI polymorphism may be associated with a moderate protective effect against CRC.     

Associations between Vitamin D Receptor (VDR) Gene Polymorphisms and Colorectal Cancer Risk and Effect Modifications of Dietary Calcium and Vitamin D in a JapanesePopulation

Much interest has been drawn to possible associations between vitamin D receptor (VDR) gene polymorphismsand colorectal cancer risk in conjunction with potentially protective effects of calcium and vitamin D. In a studyof 685 cases of colorectal cancer and 778 community controls in Japan, we examined the associations of the FokI,BsmI, ApaI, and TaqI polymorphisms with colorectal cancer risk and effect modification by dietary calciumand vitamin D. Genotypes were determined by the PCR-RFLP method. The ApaI polymorphism seemed to beassociated with a decreased risk of colorectal cancer, particularly of rectal cancer. The adjusted odds ratio ofcolorectal cancer for the ApaI AA and Aa genotypes combined versus the aa genotype was 0.83 (95% confidenceinterval [CI] 0.67-1.02), and the corresponding value for rectal cancer was 0.75 (95%CI 0.56-0.99). A decreasedrisk of colorectal cancer for the ApaI AA and Aa genotypes combined was more evident in individuals with highcalcium intake (interaction p=0.055). The FokI polymorphism seemed to be associated with a decreased risk ofcolon cancer among those with high vitamin D intake (interaction p=0.09). The BsmI and TaqI polymorphismswere unrelated to colorectal cancer risk, and the null associations were not modified by calcium or vitamin Dintake. In conclusion, the ApaI polymorphism may be associated with a decreased risk of colorectal cancer inJapanese, dependent on dietary calcium intake.     

Lack of Associations between Vitamin D Metabolism-Related Gene Variants and Risk of Colorectal Cancer

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluatedgenetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D bindingprotein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1).Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled inthis case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results:In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714),and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRCand the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status,NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants andCRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC,and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledgehas not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless,our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesisneed to be further investigated.     

Methionine Synthase Reductase Gene A66G Polymorphism is Associated with Risk of Colorectal Cancer

A hospital-based case-control study was conducted to evaluate the significance of methionine and folate related ‍polymorphisms, with 72 colon and 70 rectal cancer cases and 241 non-cancer controls. The polymorphisms examined ‍were in the genes for methionine synthase reductase (MTRR A66G), methionine synthase (MTR A2756G) and ‍methylenetetrahydrofolate reductase (MTHFR C677T and A1298C). An unconditional logistic regression model ‍was applied for estimating the odds ratios (ORs) and 95% confidence intervals (CIs). The age-sex adjusted OR for ‍the MTRR GG genotype as compared with the AA and AG genotypes was 2.77 (95% CI: 1.39-5.53, p = 0.004), whereas ‍adjusted ORs for other polymorphisms were not statistically significant. When the ORs for environment factors ‍(smoking, alcohol consumption, body-mass-index, and physical exercise) were calculated according to each ‍polymorphism, no substantial difference was observed except with the MTRR polymorphism. The ORs for the MTRR ‍GG genotype seemed to be modified by the extent of environmental exposure. In conclusion, the present study ‍showed that the GG genotype of MTRR A66G is a risk factor for colorectal cancer in Japanese, while MTHFR and ‍MTR polymorphisms are not. The conclusions, however, need further evaluation in terms of micronutrient status ‍and additional confirmatory studies are required with datasets for various ethnic groups.     

RPSA Gene Mutants Associated with Risk of Colorectal Cancer among the Chinese Population

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) inribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and387 patients with CRC was conducted in a Chinese population. Information about socio-demography and livingbehavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291)in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used forassessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotypehad a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustmentfor covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00).Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Amongthe subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC(OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects incomparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibilityto CRC and influence the protective effect of tea consumption in the Chinese population.     

Parathyroid Hormone Gene rs6256 and Calcium Sensing Receptor Gene rs1801725 Variants are not Associated with Susceptibility to Colorectal Cancer in Iran

Background: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. Materials and Methods: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. Results: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m2) cases and overweight/ obese (BMI ≥25 kg/m2) cases for the two SNPs. Conclusions: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings.     

The Common 677C>T Gene Polymorphism of Methylenetetrahydrofolate Reductase Gene is not Associated with Breast Cancer Risk

Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. A common 677C>T polymorphism in the gene for MTHFR, leading to a thermolabile enzyme with decreased activity, has been associated with reduced plasma folate levels and elevated homocysteine levels and could be a risk factor for breast cancer. In the present case-control study, MTHFR genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects. The homozygous TT genotype was found in 13.0% patients and 13.1% controls (P = n.s.). The odds ratio of TT homozygotes for breast cancer was 0.99 (95% confidence interval 0.68–1.43). The MTHFR genotype was furthermore not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. In a subgroup of 116 premenopausal patients, no increased frequency of the homozygous 677T genotype was found (13.8%). Therefore, we conclude that the MTHFR 677C>T polymorphism is not associated with individual susceptibility to breast cancer.     

维生素D及其受体在胰腺癌中的研究进展

胰腺癌是全球最致命的恶性肿瘤之一,其发病率接近死亡率。绝大多数胰腺癌患者在确诊时已属晚期,失去手术治疗机会,而放、化疗对胰腺癌的疗效并不确切,目前分子靶向治疗已成为治疗恶性肿瘤的重要手段,因此,亟需研发新的治疗靶点。大量体内外实验证明,维生素D可通过与其受体(VDR)结合发挥抗肿瘤作用。维生素D通路作为治疗胰腺癌的新靶点,已成为目前研究的一个热点。全文主要就维生素D及其受体的结构、功能、抗肿瘤作用机制以及在胰腺癌中的研究进展作一综述。     

The 870G>A Polymorphism of the Cyclin D1 Gene is not Associated with Breast Cancer

A common 870G > A polymorphism in the gene for cyclin D1, CCND1, has been linked to alternative splicing and cancer susceptibility. To analyze its role for breast cancer, we determined the CCND1 genotype in 500 breast cancer patients and 500 controls. CCND1 genotype frequencies were similar among patients and controls. The CCND1 genotype was furthermore not associated with tumor characteristics. We conclude that the CCND1 870G > A polymorphism is not associated with breast cancer.     

Serum 25-hydroxy Vitamin D Status is Not Related to Osteopenia/Osteoporosis Risk in Colorectal Cancer Survivors

Background: The incidence of colorectal cancer increases with vitamin D deficiency as shown in recentlypublished studies. In addition, prospective investigations have indicated that low vitamin D levels may beassociated with increased mortality of colorectal cancer, especially in stage III and IV cases. However, the exactincidence of vitamin D deficiency and the relation between vitamin D deficiency and osteopenia/osteporosis isstill not known. The aim of this study is to identify severity of vitamin D deficiency and absolute risk factors ofosteopenia/osteoporosis in colorectal cancer survivors. Materials and Methods: A total of 113 colorectal cancersurvivors treated with surgery and/or chemotherapy ± radiotherapy were recruited from medical oncologyoutpatient clinics during routine follow-up visits in 2012-2013. Bone mineral densitometry (BMD) was performed,and serum 25-OH vitamin D levels were also checked on the same day of the questionnaire. The patients wasdivided into 2 groups, group A with normal BMD and group B with osteopenia/osteoporosis. Results: Themedian age of the study population was 58 (40-76). Thirty (30.0%) were female, whereas 79 (70.0%) were male.The median follow-up was 48 months (14-120 months). Vitamin D deficiency was found in 109 (96.5%); milddeficiency (20-30 ng/ml) in 19 (16.8%), moderate deficiency (10-20 ng/ml) in 54 (47.8%) and severe deficiency(<10 ng/ml) in 36 (31.9%). Osteopenia was evident in 58 (51.4%) patients whereas osteoporosis was noted in 17(15.0%) . Normal BMD was observed in 38 (33.6%). No apparent effects of type of surgery, presence of stoma,chemotherapy, radiotherapy and TNM stage were found regarding the risk of osteopenia and osteoporosis.Also, the severity of the vitamin D deficiency had no effect in the risk of osteopenia and osteporosis (p=0.93). Infemale patients, osteopenia/osteoporosis were observed in 79.5% patients as compared to 60.7% of male patients(p=0.04). Conclusions: In our study, vitamin D deficiency and osteopenia/osteoporosis was observed in 96.5%and 66.4% of colorectal cancer survivors, respectively. There is no defined absolute risk factor of osteopeniaand osteoporosis in colorectal cancer survivors. To our knowledge, in the literature, our study is the first toevaluateall the risk factors of osteopenia and osteoporosis in colorectal cancer survivors.     

结直肠癌患者维生素D受体对血浆促炎性细胞因子和肠道菌群的影响

摘 要：［目的］ 研究结直肠癌患者维生素D受体（VDR）表达对血浆促炎性因子以及肠道菌群的影响情况。［方法］ 纳入初次诊断为结直肠癌的患者130例和年龄、性别成组匹配的对照（无结直肠疾病的受检者）130名,采用免疫组化的方法测量结直肠癌患者癌组织中的VDR表达水平,并将患者分为VDR高表达组以及VDR低表达组。检测研究对象血浆中促炎性细胞因子白介素-6（IL-6）、C反应蛋白（CRP）和肿瘤坏死因子受体2（sTNFRⅡ）水平,对研究对象粪便样本中细菌的16S rDNA进行测序得到肠道菌群构成与丰富度。［结果］ VDR低表达组患者血浆sTNFRⅡ与CRP显著高于对照组（P<0.001）。VDR低表达组sTNFRⅡ显著高于VDR高表达组（P=0.027）。VDR低表达组与高表达组分别与对照组相比得到的差异细菌不同,VDR低表达患者体内Fusobacterium varium、Ruminococcus torques等6种细菌有显著升高。［结论］ 结直肠癌患者体内VDR受体表达可能影响了血浆促炎性因子和肠道菌群变化。     

Serum Vitamin D Metabolites in Colorectal Cancer Patients Receiving Cholecalciferol Supplementation: Correlation with Polymorphisms in the Vitamin D Genes

Cholecalciferol (D₃) supplementation results in variable increases in serum 25(OH)D₃ levels, however, the influence of genetic polymorphisms on these variable responses is unclear. We measured serum 25(OH)D₃, 24,25(OH)₂D_3, 1,25(OH)₂D₃ and VDBP levels in 50 colorectal cancer (CRC) patients before and during 2,000 IU daily oral D₃ supplementation for six months and in 263 archived CRC serum samples. Serum PTH levels and PBMC 24-OHase activity were also measured during D₃ supplementation. TagSNPs in CYP2R1, CYP27A1, CYP27B1, CYP24A1, VDR, and GC genes were genotyped in all patients, and the association between these SNPs and serum vitamin D₃ metabolites levels before and after D₃ supplementation was analyzed. The mean baseline serum 25(OH)D₃ level was less than 32 ng/mL in 65 % of the 313 CRC patients. In the 50 patients receiving D₃ supplementation, serum levels of 25(OH)D₃ increased (p?=?0.008), PTH decreased (p?=?0.036) and 24,25(OH)₂D₃, 1,25(OH)₂D₃, VDBP levels and PBMC 24-OHase activity were unchanged. GC SNP rs222016 was associated with high 25(OH)D₃ and 1,25(OH)₂D₃ levels at baseline while rs4588 and rs2282679 were associated with lower 25(OH)D₃ and 1,25(OH)₂D₃ levels both before and after D₃ supplementation. CYP2R1 rs12794714 and rs10500804 SNPs were significantly associated with low 25(OH)D₃ levels after supplementation but not with baseline 25(OH)D₃. Our results show that D₃ supplementation increased 25(OH)D₃ levels in all patients. GC rs4588 and rs2283679 SNPs were associated with increased risk of vitamin D₃ insufficiency and suboptimal increase in 25(OH)D₃ levels after D₃ supplementation. Individuals with these genotypes may require higher D₃ supplementation doses to achieve vitamin D₃ sufficiency.     

Novel Mutations of the PARP-1 Gene Associated with Colorectal Cancer in the Saudi Population

Background: colorectal cancer (CRC) is the third most common type of cancers and the fourth leading causeof death worldwide. In Saudi Arabia, CRC accounts for 8.5% of all tumors; it ranks first among all cancersin males and third among females. The aim of this study was to link between different PARP-1 mutations andrisk of CRC in Saudi population and to determine common variants of PARP-1 in Saudi CRC patients andnormal individuals. Materials and Methods: DNA samples were isolated from fifty CRC patients and from acomparable number of control subjects then sequenced to detect different variations present in exons 3, 17, and21 of the PARP-1 gene. Results and Conclusions: When comparing the genotype and allele frequencies of alldetected SNPs in CRC patients with those in controls, we found none were significantly different for all variantseven the most common SNP in PARP-1 gene (Val762Ala). However, two novel alterations in exon 21 were foundto be associated with increased risk of CRC. The variants identified as (1) Lys933Asn [p-value 0.0318] and (2)Lys945Asn [p-value 0.0257]. Our results suggest that PARP-1 Lys933Asn and Lys945Asn alterations could beassociated with increased risk of CRC in the Saudi population.     

Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5’-UTR and 6-bp ins/del in 3’-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, weconducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsuprovince, China. TS genotypes were identified using PCR–RFLP (restriction fragment length polymorphism)methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that thedistributions of 5’-UTR genotypes in TS were significantly different between controls and male colon cases (χ2=8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk ofcolon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. Inccontrast, the 6-bp ins/del polymorphism at the TS 3’- UTR did not influence risk of the colorectal, colon andrectal cancers. When combined genotypes for both TS 5’-UTR and 3’-UTR polymorphisms were evaluated,individuals with the 5’-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men withthe 3’-UTR –6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences inTS 5’-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS3’-UTR and 5’-UTR polymorphisms in increasing risk of colon cancer among Chinese men.