Kisspeptin-54 levels are increased in patients with colorectal cancer.

BACKGROUND: Recent studies have demonstrated that Kisspeptin, the product of the metastasis suppressor gene KiSS-1, could have a role in tumor progression and invasion. In this pilot study, we investigated the association of plasma Kisspeptin-54 level with colorectal cancer (CRC). METHODS: Plasma Kisspeptin-54 levels were quantified using enzyme-immunoassay (EIA) kits from blood samples of 81 patients with CRC at their initial staging and 59 age-matched healthy controls. RESULTS: Plasma Kisspeptin-54 levels were significantly higher in CRC patients (86.2 ± 20.5) than in controls (49 ± 12.7; p < 0.005). The cutoff value for Kisspeptin-54 detection was determined as 46 ng/ml, and area under curve (AUC) value was 0.766 with sensitivity 63 %, specificity 81.4 %, positive predictive value 82.2 %, negative predictive value 61.5 %, positive likelihood ratio 3.38, and negative likelihood ratio 0.46. Increased plasma Kisspeptin-54 levels were significantly correlated with nodal involvement of CRC (Spearman, rs = 0.345, p = 0.002). Kisspeptin-54 was also found to be an independent predictive marker for lymph node metastases of CRC (p = 0; Exp(B): 2.053; 95 % CI, 1.255-2.851). CONCLUSIONS: Our results reveal that plasma Kisspeptin-54 measurement could be a useful diagnostic and prognostic parameter for CRC. Further prospective evaluation is needed to validate these findings and to establish the clinical usefulness of Kisspeptin-54 for CRC diagnostics.

Is MMP-7 gene polymorphism a possible risk factor for chronic obstructive pulmonary disease in Turkish patients.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease that leads to fixed narrowing of small airways and alveolar wall destruction (emphysema). This study was performed to test the association between MMP-7 (rs155668818) and MMP-12 (rs56184183) polymorphisms in the MMP-7 gene and COPD risk and its severity in the Turkish population. MMP-7 and MMP-12 polymorphisms were genotyped in 85 patients with COPD and 73 healthy control subjects using real-time polymerase chain reaction analysis. There were significant differences in the distribution of MMP-7 genotypes but not in the frequencies of these alleles between COPD patients and controls (p=0.009, p=0.102, respectively). The MMP-7 AA genotype was found to be associated with an increased risk of COPD (p=0.004; odds ratio: 2.576; confidence interval: 1.297-5.119). The lowest values of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC in patients with GG homozygosity were determined and these values were statistically significant compared to the control subjects (p<0.001, p<0.001, p<0.001). When the present study groups were analyzed for MMP-12 polymorphism, it was found that all the subjects had wild-type genotype for this polymorphism. These findings have suggested that MMP-7 polymorphism might be associated with the risk and progression of COPD in the Turkish population.

Cyclooxygenase-2 gene and lung carcinoma risk.

In this study, we aimed to investigate a possible association of the COX-2 polymorphisms with the risk of developing lung carcinoma. COX-2 (-765G→C; -1195A→G) gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism in 118 healthy individuals and 231 patients with lung carcinoma. The present study was the first that addressed the role of the COX-2-765G→C and -1195A→G polymorphisms in lung carcinoma in Turkish population. In the present study, we found that the frequencies of GG, CC, and CG genotypes of COX-2-765G→C and AA, GG, and AG genotypes of -1195A→G in our control group were 0.22, 0.22, 0.55 and 0.59, 0.0, 0.40, respectively. These frequencies in patient group were 0.34, 0.07, 0.58 and 0.74, 0.04, 0.24, respectively. There were statistically significant differences in COX-2-765G→C (P=0.0002) and -1195A→G genotypes (P=0.007) between the controls and patients. We found that individuals carrying -765 GG genotype and -765 G allele of COX-2 or 1195 AA genotype of COX-2 and -765G: -1195A haplotype had an increased risk for the development of lung carcinoma. In contrast, individuals with -765 CC, -1195 AG genotypes and -1195 G allele of COX-2 seem to be protective from lung carcinoma. We suggest that the COX-2-765G→C and -1195A→G genotypes may be a risk factor for lung carcinoma.

CCND1 and CDKN1B polymorphisms and risk of breast cancer.

BACKGROUND AND OBJECTIVES: Previous studies have shown alterations in the cell cycle regulatory proteins in breast carcinomas. However, the results of these studies remain controversial. Cyclin D1 (CCND1) and p27(KIP1) (CDKN1B) are two essential regulators of cell cycle progression. This study aimed to investigate the associations of CCND1 A870G and CDKN1B C79T polymorphisms with breast cancer risk. PATIENTS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype and allelic frequencies of polymorphisms. Seventy-eight breast cancer patients and 84 age-matched healthy controls were included in the study. RESULTS: Frequencies of CT genotype and T allele of CDKN1B were found to be higher in breast cancer patients than in controls (p=0.013, OR: 1.514 95% CI: 1.086-2.114.15; p=0.007, OR=1.496; 95% CI: 1.111-2.014, respectively). The frequency of AA genotype of CCND1 was decreased in hormone receptor- (estrogen and progesterone receptors) negative patients with breast cancer (p<0.049, OR=0.286; 95% CI: 0.071-1.142) CONCLUSIONS: Even though CDKN1B polymorphism appears to be an important predictive factor for breast cancer risk and CCND1 polymorphism may be a prognostic biomarker for breast cancer, further investigations with larger study groups are needed to fully elucidate the role of CCND1 and CDKN1B polymorphisms in the development and prognosis of breast cancer.

Genetic variants of vascular endothelial growth factor and risk for the development of endometriosis.

BACKGROUND/AIMS: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated. PATIENTS AND METHODS: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes. RESULTS: The VEGF +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 G/C polymorphisms (D': 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). CONCLUSION: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis.

Possible associations of APE1 polymorphism with susceptibility and HOGG1 polymorphism with prognosis in gastric cancer.

BACKGROUND: Multiple genetic and epigenetic alterations in several genes are implicated in the multistep process of human gastric carcinogenesis. In this study, we examined the polymorphisms of six DNA repair genes: APE1, HOGG1, XRCC1, XRCC3, XPD, and XPG in patients with gastric cancer (GC). PATIENTS AND METHODS: Forty patients with GC and 247 controls were included in this study. DNA polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method. RESULTS: The frequency of the Asp/Glu genotype and Glu allele of APE1 in patients with GC was significantly higher than in the control group (p=0.05). We also observed a higher frequency of the Ser/Ser genotype of HOGG1 in grade III tumors, and in tumors with metastasis to adjacent tissue and solid organs (p<0.05). CONCLUSION: Our results suggest that (i) APE1 gene polymorphism may be associated with GC risk and (ii) HOGG1 gene polymorphism may be informative in the prognosis of GC.