Association between laryngeal squamous cell carcinoma and polymorphisms in tumor necrosis factor related apoptosis induce ligand (TRAIL), TRAIL receptor and sTRAIL levels.

The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

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.

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.