Tanzeela Khan

Association of a VDR Gene Polymorphism with Risk of Colorectal Cancer in Kashmir

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

Polymorphisms in the 3′UTR of the human leptin gene and their role in hypertension

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3′ flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2±5.12) and low (20.13±1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3′UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p≤0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3′ flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.

ECRG1 and Its Relationship with Esophageal Cancer: A Brief Review

Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC.

Mitteilungen onkologischer Gesellschaften· Reports of Oncological Societies

Die Prognose von Patienten mit metastasierten kolorektalen Karzinomen ist weiterhin schlecht und liegt trotz Einsatz neuerer Substanzen im Median bei 20–24 Monaten. Die aktuell wirkungsvollsten Chemotherapien bestehen aus Kombinationsschemata von 5-Fluorouracil (5-FU) mit Irinotecan oder Oxaliplatin. Neben diesen Chemotherapeutika ist eine neue Klasse zielgerichteter molekularer Substanzen entwickelt worden, die z.B. die Angiogenese hemmen oder bestimmte Wachstumsfaktoren bzw. deren Rezeptoren blockieren und so eine antineoplastische Wirkung entfalten sollen. Die Vorstellung ist, dass z.B. mit spezifischen Antikorpern nur solche Tu morzellen gezielt angegriffen und in ihrem Wachstum gehindert werden, die die entsprechenden Rezeptoren besitzen. Die wichtigsten bislang zugelassenen biologischen Substanzen sind Bevacizumab, ein monoklonaler Antikorper gegen den Va scular Endothelial Growth Factor, oder Cetuximab, ein Antikorper gegen den Epidermal Growth Factor Receptor (EGFR oder ErbB1) [De Roock, et al. 2007]. In Kombination mit konventionellen Chemotherapeutika konnen Ansprechraten bis 60% erreicht und dadurch das progressionsfreie Uberleben und zum Teil das Gesamtuberleben verlangert werden. Die Suche nach neuen zielgerichteten Therapien hat dazu gefuhrt, dass derzeit eine ganze Reihe neuer Substanzen in klinischen Therapiestudien gepruft werden, mit zum Teil viel versprechenden Ansatzen. Allen ist gemeinsam, dass selektiv Tu morzellen (oder beispielsweise das zum Tumor gehorige Gefassystem) angesteuert und zielgenau behandelt werden sollen, die Rezeptoren aufweisen, gegen die der Antikorper gerichtet ist. Ein neuer, voll humanisierter Antikorper, der ebenfalls fur den EGF-Rezeptor spezifisch ist [Berlin et al. 2006], Panitumumab, wurde vor kurzem ebenfalls zugelassen.

Title Page / Contents / Imprint / Guidelines

S. Al-Batran, Frankfurt/M. C. Berking, München C. Bokemeyer, Hamburg M. Borner, Bern T. Cerny, St. Gallen H. T. Eich, Münster A. Engert, Köln M. Fassnacht, München B. Groner, Frankfurt/M. V. Heinemann, München M. Hentrich, München R. D. Issels, München W. Janni, Ulm U. R. Kleeberg, Hamburg H. Lang, Mainz M. Moehler, Mainz M. Schuler, Essen R. Stupp, Zürich M. Theobald, Mainz R. Thomas, Köln U. Wedding, Jena J. A. Werner, Marburg O. Zivanovic, New York