Most colorectal cancers arise from adenomatous polyps or certain hyperplastic polyps. Only a few studies have investigated potential genetic modifiers of the associations between meat intake and polyp risk, and results are inconsistent. Using data from the Tennessee Colorectal Polyp Study, a large colonoscopy-based study, including 1,002 polyp cases (557 adenoma only, 250 hyperplastic polyp only, 195 both polyps) and 1,493 polyp-free patients, we evaluated the association of colorectal polyp risk with carcinogen exposure from meat and genetic polymorphisms in enzymes involved in heterocyclic amine (HCA) metabolism, including N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2), cytochrome P450 1A2 (CYP1A2), and aryl hydrocarbon receptor (AhR). Data on intake levels of meats by preparation methods, doneness preferences, and other lifestyle factors were obtained. Fourteen single nucleotide polymorphisms in the AhR, CYP1A2, NAT1, and NAT2 genes were evaluated. No clear association was found for any polymorphisms with polyp risk. However, apparent interactions were found for intake of meat and HCAs with AhR, NAT1, and NAT2 genotypes, and the interactions were statistically significant for the group with both adenomatous and hyperplastic polyps. Dose-response relationships with meat or HCA intake were found only among those with the AhR GA/AA (rs2066853) genotype, NAT1 rapid, or NAT2 rapid/intermediate acetylators but not among those with other genotypes of these genes. This doseresponse relationship was more evident among those with both AhR GA/AA and the NAT1 rapid acetylator than those without this genotype combination. These results provide strong evidence for a modifying effect of metabolizing genes on the association of meat intake and HCA exposure with colorectal polyp risk. (Cancer Epidemiol Biomarkers Prev 2008;17(2):320 -9)

Background Bladder cancer (BC) is the 5th most common cancer in the USA. Non-muscle invasive bladder cancer represents about 70% of all cases and has generally a favorable outcome. However, recurrence rates as high as 60 to 70% and progression rates of 10 to 20% necessitate intensive surveillance with cystoscopy. The invasiveness and high cost of cystoscopy poses significant burden on BC patients as well as on the healthcare system. In this study we test the feasibility of a simple, sensitive, and non-invasive detection of BC using Bladder CARE test in urine samples. Results Urine from 136 healthy and 77 BC subjects was collected using the at-home Bladder CARE Urine Collection Kit and analyzed with Bladder CARE test. The test measures the methylation level of three BC-specific biomarkers and two internal controls using methylation-sensitive restriction enzymes coupled with qPCR. Bladder CARE showed an overall sensitivity of 93.5%, a specificity of 92.6%, and a PPV and NPV of 87.8% and 96.2%, respectively. Bladder CARE has an LOD as low as 0.046%, which equates to detecting 1 cancer cell for every 2,200 cells analyzed. We also provided evidence that bisulfite-free methods to assess DNA methylation, like Bladder CARE, are advantageous compared to conventional methods that rely on bisulfite conversion of the DNA. Conclusion Highly sensitive detection of BC in urine samples is possible using Bladder CARE. The low LOD of the test and the measurement of epigenetic biomarkers make Bladder CARE a good candidate for the early detection of BC and possibly for the routine screening and surveillance of BC patients. Bladder CARE and the at-home urine sample collection system have the potential to (1) reduce unnecessary invasive testing for BC (2) reduce the burden of surveillance on patients and on the healthcare system, (3) improve the detection of early stage BC, and (4) allow physicians to streamline the monitoring of patients.

Background:There are few cases of choriocarcinoma metastases to the spine that have been reported. Most occurrences are in women with the gestational form of the tumor, and these now exhibit a very high remission rate with chemotherapeutic treatment, typically circumventing the need for spinal surgery.Case Description:In an effort to better understand treatment options for those rare instances when choriocarcinoma does find its way into the spine, we have synthesized a comprehensive literature review on the clinical cases of choriocarcinoma spinal metastases. We also describe our unique experience and decision-making involving the first reported case of surgical treatment of non-gestational choriocarcinoma spinal metastases in a male patient.Conclusion:Spinal surgery has a limited role in metastatic choriocarcinoma, but there is the potential for improving neurologic decline even in the rare and aggressive male variant of this disease.

Frankia are gram-positive, filamentous bacteria capable of fixing atmospheric dinitrogen in symbiosis with a wide variety of woody plants and shrubs. Some isolates of Frankia harbor plasmids of 8.5 (pFQ11) and 22.4 kb (pFQ12) that have no known function but are transmitted through many generations in culture. We have sequenced the 22 437-bp pFQ12 plasmid that is present in isolates CpI1 and ArI3. This sequence, with 76% G+C, is almost totally unrelated to that of pFQ11 found in the same cells. However, four regions of identity, 40-90 bp each, are dispersed around the plasmids. The 22.4-kb plasmid has >50 open reading frames (ORFs) that encode putative proteins of more than 100 amino acids, with the largest being 2226 amino acids. Twenty of these ORFs are likely to encode proteins based on their codon bias as determined by two different algorithms. Transcripts from nine of these regions have been identified by reverse transcriptase-polymerase chain reaction (RT-PCR) or filter hybridization. The two Frankia plasmids each encode a protein similar to the korSA protein that regulates transmission of pSAM2 in Streptomyces. The origin of replication (ORI) region of pFQ12 was localized by intrastrand AT and GC equivalence switch. It includes a 40-bp, intergenic, A+T-rich region that has a strong identity in pFQ11.Key words: ORI analysis, RT-PCR, Glimmer, DNA sequence.Résumé : Frankia est une bactérie filamenteuse gram-positive capable de fixer le diazote atmosphérique lorsqu'en symbiose avec une grande variété de plantes ligneuses et d'arbustes. Certains isolats de Frankia contiennent des plasmides de 8,5 (pFQ11) et 22,4 kb (pFQ12) qui n'ont aucune fonction connue mais qui sont transmises à travers plusieurs gé-nérations en culture. Nous avons séquencé le plasmide pFQ12 de 22 437 pb qui est présent dans les isolats CpI1 et ArI3. Cette séquence, constituée à 76 % de G+C, est presque totalement non apparentée à celle de pFQ11 retrouvé dans les mêmes cellules. Cependant, quatre régions d'identité, de 40-90 pb chaquene, sont dispersées autour des plasmides. Le plasmide de 22,4 kb contient >50 cadres de lecture ouverts « CLO » dant des protéines putatives de plus de 100 acides aminés, la plus grosse étant composée de 2226 acides aminés. Vingt d'entre ceux-ci sont susceptibles de coder des protéines, en se basant sur leur préférence en codons tel que déterminé par deux algorithmes différents. Les transcrits de neuf de ces régions ont été identifiés par RT-PCR ou par hybridation sur filtre. Les deux plasmides de Frankia codent chacune une protéine semblable à la protéine korSA qui contrôle la transmission de pMSA2 dans Streptomyces. La région ORI (« origin of replication ») de pFQ12 a été localisée par la transition de l'équivalence en AT et GC dans l'ADN. Elle renferme une région intergénique AT-riche de 40 pb qui démontre une forte analogie avec pFQ11.Mots clés : analyse ORI, RT-PCR, Glimmer, séquence d'ADN.[Traduit par la Rédaction] 617 John et al.