Coexistence of K-ras mutations and HPV infection in colon cancer

BACKGROUND: Activation of the ras genes or association with human papillomavirus infection have been extensively studied in colorectal cancer. However, the correlation between K-ras mutations and HPV in colorectal cancer has not been investigated yet. In this study we aimed to investigate the presence of K-ras mutations and their correlation with HPV infection in colon cancer. METHODS: K-ras mutations were analyzed by a mutagenic PCR assay and digestion with specific restriction enzymes to distinguish the wild-type and mutant codons. HPV infection was analyzed by PCR amplification and hybridization with specific probes by Southern blotting. Stattistical analyses were performed by the chi-square and Fisher's exact tests RESULTS: HPV gene fragments were detected in 43 tumors and 17 normal tissue samples. HPV 18 was the prevalent type in the tumor tissue. A mutation at codon 12 of the K-ras gene was present in 31 patients. 56% of the HPV-positive tumors also harbored a K-ras mutation. Codon 13 mutations were not observed. These data indicate that infection with high risk HPV types and mutational activation of the K-ras gene are frequent events in colorectal carcinogenesis. CONCLUSION: Our findings suggest that mutational activation of the K-ras gene is a common event in colon carcinogenesis and that HPV infection may represent an important factor in the development of the premalignant lesions leading to the neoplastic phenotype

Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk

Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer

<p>Abstract</p> <p>Background</p> <p><it>TP53 </it>is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of <it>Arg72Pro </it>and <it>PIN3 Ins16bp </it>polymorphisms in <it>TP53 </it>gene as genetic susceptibility and predictive markers to breast cancer.</p> <p>Methods</p> <p>We analysed DNA samples from 264 breast cancer patients and 440 controls, for <it>TP53 Arg72Pro </it>and <it>PIN3 Ins16bp </it>polymorphisms using PCR-RFLP.</p> <p>Results</p> <p>We observed that women with <it>A2A2 </it>genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60–12.0; p = 0.004; OR = 3.88, 95% CI 1.18–12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between <it>TP53 Arg-A2 </it>haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08–4.06; p = 0.028). Furthermore, both <it>TP53 </it>polymorphisms are associated with higher incidence of lymph node metastases.</p> <p>Conclusion</p> <p>Our findings suggest <it>TP53 PIN3 Ins16bp </it>polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.</p

Utility of c-erbB-2 expression in tissue and sera of ovarian cancer patients

In this study expression of the c-erbB-2 gene in tumors and healthy tissue of patients with ovarian cancer was investigated. Serum c-erbB-2 protein levels were also determined. Elevated serum values were observed in 45% of patients. c-erbB-2 protein levels in the armors were significantly higher than in healthy tissue. Overexpression of the protein was observed in 60% of patients. However no association was found between the clinical variables and tumor c-erbB-2 expression. This is the first study in the literature investigating the c-erbB-2 oncoprotein levels in the normal and tumor tissue. We conclude that the role of the c-erbB-2 gene in ovarian cancer warrants further studies

Changes in enzymatic antioxidant defense system in blood and endometrial tissues of women after menopause

The effects of menopause on antioxidant enzyme activities were investigated in blood and endometrial tissues of women. Endometrial pieces were obtained from pre-or postmenopausal patients who had hysterectomy due to descendus or prolapsus uteri. In endometrium homogenates, both cytosolic superoxide dismutase (CuZn-SOD) and catalase (CAT) activities were similar in pre-or postmenopausal women (median ages 41 and 64, respectively); whereas GPx (glutathione peroxidase) activity was significantly decreased (p< 0.001). Activity of these enzymes were also compared in the blood of premenopausal and late menopausal women, and only GPx activity was found significantly low (p< 0.01). Subsequent measurements were carried out in blood of healthy menopausal women who were in the same age intervals with the premenopausal subjects studied, and GPx activity was found indifferent in two groups, indicating that the decrement is due to aging rather than the change in hormonal status. CuZn-SOD activity was highest in blood of late menopausal group compared with those in both premenopausal and early menopausal group, giving a significant difference with the latter (p< 0.001). In other words, SOD activity was increased in menopausal women at an older age, showing a diverse change with GPx activity

Relevance of anti-Mullerian hormone on in vitro fertilization outcome

Purpose: The aim of this study was to investigate the relevance of serum and follicular anti-Mullerian hormone (AMH) concentrations on ovarian reserve and clinical pregnancy. Materials and Methods: Thirty patients were prospectively included in this study. Serum AMH levels were quantitatively measured on the follicle aspiration day. Retrieving less than five oocytes was defined as poor response. Eleven days after embryo transfer, beta-human chorionic gonadotropin (beta-hCG) level in the blood was measured. Two weeks after the beta-hCG test, a clinical pregnancy was confirmed by transvaginal ultrasound (TVUS). Results: There was a statistically significant correlation between serum AMH and number of retrieved oocytes (p = 0.024). There was a correlation between the number of retrieved oocytes and baseline antral follicle count (AFC), between ovarian reserve and baseline follicle-stimulating hormone (FSH), and between ovarian reserve and serum AMH (p < 0.05). Serum AMH cut-off value for the normal ovarian reserve was calculated as 0.37ng/m1 (sensitivity 71.43%, specificity 66.67%, positive prediction 83.33%, negative prediction 50%). Conclusion: Increasing use of serum AMH will be of considerable benefit. Consequently, the observed positive correlation between serum AMH and ovarian reserve will require larger sampling to refine the role of AMH