Association of vitamin D receptor gene polymorphisms with colon cancer.

OBJECTIVE: In this study, we investigated the association of two vitamin D receptor (VDR) polymorphisms BsmI and TaqI with colon cancer in a Caucasian population. METHODS: The VDR gene polymorphisms BsmI and TaqI were detected by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-genotyping assays by using endonucleases BsmI and TaqI, and an agarose gel electrophoresis technique in a series of 43 colon cancer patients and 42 healthy controls. RESULTS: Allele frequencies and genotype distributions were found to be similar in both cases and controls. When homozygous carriers and heterozygotes were combined for each allele, alleles B and T were found to be more common in the control group (p=0.039, χ(2)=4.276, odds ratio [OR]=0.312, 95% confidence interval [CI]=0.100-0.973 and p=0.039, χ(2)=4.258, OR=0.254, 95% CI=0.064-1.000, respectively). When genotypes were analyzed as pairs, the Bb/TT variant was higher in the control group at a statistically high significance (p=0.001, χ(2)=11.854, OR=0.122, 95% CI=0.032-0.460). CONCLUSION: The alleles B and T and the genotype combination Bb/TT were found to be higher in the control group, and thus BsmI and TaqI polymorphisms of the VDR gene may be possible risk factors for colorectal carcinogenesis.

The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population.

Endothelial nitric oxide synthase (eNOS), coded by the gene NOS3, may play an important role in uncontrollable cellular growth in several cancer types. Our study was performed to test the association between Glu298Asp polymorphisms in the NOS3 gene and colorectal cancer risk and progression. In this study, NOS3 Glu298Asp polymorphism was genotyped in 84 patients with colorectal cancer and 99 healthy subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There were significant differences in the distribution of NOS3 genotypes and frequencies of the alleles between colorectal cancer patients and controls (P = 0.016, P = 0.006, respectively). The increased frequency of NOS3 Glu298Asp homozygotes genotypes in patients who had advanced tumour stage was statistically significant (P = 0.042). Our findings have suggested that NOS3 Glu298Asp polymorphism might be associated with the risk and progression of colorectal cancer in Turkish population.

Genetic variants of SDF-1 and CXCR4 genes in endometrial carcinoma.

In this study, we aimed to investigate a possible association between the Stromal cell-derived factor-1 (SDF-1) and CXCR4 polymorphisms and the risk of developing endometrial carcinoma. SDF-1 3'A and CXCR4 gene polymorphisms was performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 139 healthy individuals and 113 patients with endometrial carcinoma. In our study groups SDF-1 3'A AA genotype frequency was higher in patients that of controls and individuals who had AA genotype showed a 2.6-fold increased risk for endometrial cancer. The carriers of CXCR4 T allele were higher in patients compared with controls and individuals who had TT genotype had a 2.5-fold high risk for endometrial carcinoma. Our finding suggest that there was no significant association between the (SDF-1) and CXCR4 polymorphisms and endometrium cancer risk. Further studies in a larger population are needed to better elucidate the role of (SDF-1) and CXCR4 gene polymorphisms in the risk of endometrial carcinogenesis. To the best of our knowledge, this is the first study to show such an association.

Association of vitamin D receptor Taq I polymorphism and susceptibility to oral squamous cell carcinoma.

BACKGROUND: It has been hypothesised that vitamin D receptor (VDR) gene polymorphisms may influence both the risk of cancer occurrence and prognosis. MATERIALS AND METHODS: The distribution of VDR Taq I polymorphism in 64 patients with OSCC was determined by polymerase chain reaction based restriction fragment length polymorphism (RFLP) and compared with that of 87 healthy controls. RESULTS: There was a significant difference in the distribution of VDR Taq I genotypes between OSCC patients and healthy controls. Patients with the VDR Tt genotype were found to be at significantly higher risk for OSCC than those with other genotypes (p=0.036). In particular, female OSCC patients were at higher risk (p<0.001) for oral cancer. CONCLUSION: These results suggest that the VDR Taq I polymorphism may be associated with susceptibility to OSCC. Female predilection of the OSCC risk in association with VDR gene polymorphism should also be investigated.

The influence of cyclin D1 A870G polymorphism on colorectal cancer risk and prognosis in a Turkish population.

BACKGROUND: Cyclin D1, encoded by the gene CCND1, is a regulatory protein in the cell cycle transition from G(1) phase to S phase. A common polymorphism (A870G) at codon 242 affects splicing of the CCND1 transcript and may cause uncontrollable cellular growth. The present study was performed to test the association between A870G polymorphisms in the CCND1 gene and colorectal cancer risk and progression. PATIENTS AND METHODS: The 870 A>G polymorphism in the cyclin D1 gene was genotyped in a Turkish colorectal cancer case-control population including fifty-seven cases (35 male, 22 female; mean age + or - SD: 59.33 + or - 13.7 years) and 117 controls (63 male, 54 female; mean age + or - SD: 54.4 + or - 12.2 years) using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Genotype frequencies of our patients and controls both confirmed to the Hardy-Weinberg equilibrium. There was no difference in the distribution of CCND1 genotypes and frequencies of the alleles A (59.6% versus 49.6%) and G (40.4% versus 50.4%) in the colorectal cancer patients and controls, respectively. Women homozygous for the cyclin D1 870 GG genotype showed an increased risk for developing colorectal cancer compared to those with the AG+AA genotypes and this result was statistically significant (OR 5.568, 95% CI 1.270-24.417, p=0.02). On the other hand, the cyclin D1 GA genotype was associated with distant metastasis (p=0.016). CONCLUSION: Our findings suggest that genetic variants of A870G might be associated with distant metastasis and also gender.

Association between CDKN1A Ser31Arg and C20T gene polymorphisms and colorectal cancer risk and prognosis.

BACKGROUND: CDKN1A (p21(WAF1/CIP1)) plays an important role in cell cycle regulation. Somatic alterations in genes which regulate cell division have been shown to be related to different types of cancer prognosis and survival. The purpose of this study was to investigate the effect of the CDKN1A Ser31Arg and C20T gene polymorphisms in Turkish patients with colorectal cancer. PATIENTS AND METHODS: CDKN1A Ser/Arg and C20T polymorphisms were studied in 53 patients with colorectal cancer and 64 healthy controls. Genomic DNA was amplified by polymerase chain reaction (PCR) and genotypes were determinated by the restriction fragment length polymorphism (RFLP) method. RESULTS: There were statistically significant differences in the distribution of CDKN1A Ser/Arg genotypes and allele frequencies between colorectal cancer patients and healthy controls (p=0.040 and p=0.01, respectively). CDKN1A C20T genotype frequency did not show any significant differences between patients and controls. We combined the results for C20T and Ser31Arg polymorphisms and observed that a lower risk of colorectal cancer was associated with CT/SerArg combined genotypes compared to controls and this difference was statistically significant (p=0.024; odds ratio (OR)=0.322, 95% confidence interval (CI)=0.114-0.912). C20T C allele and SerSer genotypes significantly increased risk compared to other combined genotypes (p=0.034; OR=1.265, 95% CI=1.020-1.569). CONCLUSION: The results of present study demonstrated that, potentially, CDKN1A functional polymorphisms may contribute to the risk of colorectal cancer in Turkish.

Polymorphisms in the microsomal epoxide hydrolase gene: role in lung cancer susceptibility and prognosis.

AIMS AND BACKGROUND: The aim of this study was to investigate the relationship between EPHXI exon 3 Tyr113His and exon 4 His139Arg polymorphisms, predicted microsomal epoxide hydrolase (mEH) activity, and lung cancer development. mEH is a protective enzyme involved in oxidative defences against a number of environmental chemicals and pollutants, but it is also responsible for the xenobiotic activation of carcinogens. METHODS: We investigated the two polymorphisms of the mEH gene (EPHX1) in 58 lung cancer patients and 41 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The exon 3 Tyr113His polymorphism was associated with lung cancer (P < 0.001). The frequency of the His113His homozygote genotype in exon 3 was significantly increased in patients compared with controls (P < 0.001). In contrast, there was no significant difference in exon 4 polymorphisms between patients and controls. When the exon 3 and 4 polymorphisms were considered together, the combined EPHX1 His113His113/His139His139 genotype (very low predicted enzyme activity) was found to be associated with an increased risk of lung cancer (P = 0.044, OR = 3.063, CI = 0.932-10.069). We observed that patients with T3 + T4 tumors had an approximately 3-fold higher risk of the Tyr113/His113 genotype than patients with T1 + T2 tumors. Lung cancer patients carrying a heterozygote Tyr113/His 113 genotype had a 2-fold increased risk of lymph node metastases (P = 0.051). CONCLUSION: These findings suggest that the exon 3 Tyr113His and exon 4 His139Arg polymorphisms of EPHXI may be associated with a increased risk of lung cancer and a worse prognosis.

Is there any correlation between TNF-related apoptosis-inducing ligand (TRAIL) genetic variants and breast cancer?

INTRODUCTION: TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand and also a member of the TNF superfamily. We aimed to investigate the possible relationship between TRAIL and breast cancer. Here, we report the results of the first association study on genetic variation in the TRAIL gene and its effect on breast cancer susceptibility and prognosis. MATERIAL AND METHODS: A C/T polymorphism at 1595 position in exon 5 of the TRAIL gene was genotyped in a Turkish breast cancer case-control population including 53 cases (mean age: 55.09 ±11.63 years) and 57 controls (mean age: 57.17 ±17.48 years) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: There were no differences in the distribution of TRAIL genotypes and frequencies of the alleles in the breast cancer patients and controls. A heterozygous TRAIL CT polymorphism in exon 5 was present in 8.3% of tumour stage III-IV and 48.8% of stage I-II patients, and in 42.1% of controls. The reduced frequency of this genotype in patients who had advanced tumour stage was statistically significant (p = 0.017). CONCLUSIONS: Our findings indicate that genetic variants of TRAIL at position 1595 in exon 5 might be associated with progression of breast cancer.

Breast cancer and cyclin D1 gene polymorphism in Turkish women.

BACKGROUND: Cyclin D1 protein plays an important part in regulating the progress of the cell during the G(1) phase of the cell cycle. It has been suggested that G870A polymorphism at the exon4/intron4 splicing region of the CCND1 gene may play a role in tumorigenesis and invasiveness. PATIENTS AND METHODS: A case-control study was performed to test the association between G870A polymorphisms in the CCND1 gene and breast cancer risk and cancer progression. For this purpose, 38 patients with breast cancer and 64 healthy women controls were included in the study. The CCND1 G870A polymorphisms in our study groups were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using peripheral blood samples. RESULTS: A significant difference was found in the distribution of the GG, AG and AA genotypes between the patient group and the control group (p=0.021). A lower risk (odds ratio 0.435, 95% confidence interval 0.223-0.846) was found to be associated with heterozygote AG individuals when compared with homozygote allele carriers in breast cancer. The cyclin D1 A870G genotype was associated with capsular invasion (p=0.02). CONCLUSION: The risk of breast cancer development and prognosis may be associated with genetic variation in the CCND1 genotype, which may be used as a biomarker for further studies.

Role of L-MYC polymorphism in oral squamous cell carcinoma in Turkey.

BACKGROUND: An association between restriction fragment length polymorphism (RFLP) of known oncogenes and a predisposition to develop cancer has been postulated. Our aim was to test the hypothesis that there was an association between the L-MYC S allele in oral squamous cell carcinoma (OSCC) and a predisposition for the disease. PATIENTS AND METHODS: The distribution of L-MYC polymorphism in 80 patients with OSCC was determined by polymerase chain reaction-based RFLP and compared with that of 60 healthy controls. RESULTS: There was no significant difference between patients with OSCC and healthy controls. Patients with the L-MYC S allele and a positive family history of cancer were found to be 1.74 times more at risk for OSCC than those with any other genotype (95% confidence interval=0.88-3.45). Moreover, tumor recurrence was higher among individuals carrying a L-MYC S allele than those with any other allele type. CONCLUSION: L-MYC polymorphism was not a significant marker for predicting susceptibility to OSCC in this population but may be a useful marker for identifying patient susceptibility to tumor recurrence and to developing OSCC, especially in individuals having a family history of cancer.

Fas-1377 A/G polymorphism in lung cancer.

BACKGROUND: Reduced expression of Fas and/or increased expression of FasL is known to exist in some cancer types including lung cancer, so the Fas/FasL system may play a role in the course of cancer. Lack of cell surface Fas expression is one of the main routes of apoptotic resistance in tumor formation and progression. Functional mutations in the Fas gene that impair apoptotic signal transduction are associated with susceptibility to various types of cancer. In this study, we focused on lung cancer. PATIENTS AND METHODS: The genotypic tendencies that may occur due to a specific point mutation (Fas-1377 G -->A) on promoter region for Fas were evaluated. RESULTS: We did not find any relationship between Fas-1377 G-->A polymorphism and lung cancer. But there was a significantly higher number of AG patients who smoked than GG ones. CONCLUSION: There was no relationship between Fas-1377 G-->A polymorphism and lung cancer, but it was statistically significant that smoking might increase the possibility of creating lung cancer in AG genotypes more than in other genotypes.

Investigation of the VDR gene polymorphisms association with susceptibility to colorectal cancer.

The effects of 1,25-dihydroxyvitamin D3 are mediated by binding to a specific intracellular vitamin D receptor (VDR), which has been identified in a variety of tissues. Certain polymorphisms in the VDR gene have been associated with various neoplasms. For this purpose, we studied whether VDR TaqI or FokI genotype are associated with serum 25-hydroxyvitamin D3 in 52 controls and 26 patients with colorectal cancer. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis tecniques were used to detect these polymorphisms. We measured 25-hydroxyvitamin D3 serum levels by ELISA. The frequencies of the FF, Ff and ff genotypes were 73.1%, 11.5%, 15.4% in colorectal cancer patients and 38.5%, 59.6%, 1.9% in healthy controls, respectively. We observed the T allele in 50% and 58.7%, and the t allele in 50% and 41.3% of colorectal cancer patients and the control group, respectively. In patients with colorectal cancer who have TT genotype, serum 25-hydroxyvitamin D3 level was lower than those with Tt/tt genotype (p:0.016). The frequency of subjects with TTFf or TtFf genotype in colorectal cancer patients was very low compared with all other genotypes (OR = 0.112; 95%CI 0.030-0.419). These data suggest that VDR TtFf or TTFf genotypes may protect against colorectal carcinogenesis. However, further studies are necessary to confirm these findings.