Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia.

Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.

Exposure to gamma rays induces early alterations in skin in rodents: Mechanical, biochemical and structural responses.

In this study, the effect of gamma rays has been investigated on the normal rat skin using biomechanical, biochemical and histological techniques. Seventeen male Wistar albino rats were divided into two groups (control (n=7) and irradiated (n=10)). The irradiated group was treated with a (60)Co gamma source at a dose of 10Gy at room temperature. Skin biomechanics were measured with tensile test using biomaterial testing machine and maximum load, stiffness, energy absorption capacity, ultimate stress, ultimate strain and elastic modulus were calculated. In the irradiated group, energy, strain and toughness were significantly lower than in the control group (p<0.05). However, strength, displacement, stiffness, stress and elastic modulus were similar to that of the control group (p>0.05). Catalase (CAT) activities and the levels of malondialdehyde (MDA) in the skin of rats were measured using the biochemical methods. MDA levels significantly increased whereas CAT activities decreased in the irradiated group as compared with the control group (p<0.05). Diameters of collagen fibers were measured by transmission electron microscopy. There was no significant difference (p>0.05) between control and irradiated groups for collagen fiber diameter. Thickness of epidermis was significantly lower than the control group. There were no changes in the epidermis between the irradiated group and the control group ultrastructurally. The results of this study show that the gamma irradiation has a significant effect on normal healthy skin.

Prenatal diagnosis of sickle cell anemia in twin pregnancies and identification by VNTRs.

BACKGROUND: Sickle cell anemia (SCA) is an inherited disorder of hemoglobin synthesis that is characterized by life-long severe hemolytic anemia, attacks of pain crisis, and chronic organ system damage. In this study, prenatal diagnosis was performed to three couples (families A, B, and C) with twin pregnancies who were at risk for SCA. METHODS: The SCA carrier state of the couples were confirmed at molecular level. Chorionic villus samples (CVS) of twins were obtained at 10-12 weeks of gestation. Amplification refractory mutation system (ARMS) and restriction fragment length polymorphism (RFLP) techniques were applied to determine and confirm the presence of the sickle cell anemia of the fetuses. Identification of each twin, confirmation of parentage and elimination of maternal contamination of chorionic villus samples were ruled out by variable number of tandem repeats (VNTR) analysis of four different loci [D1S80 (pMCT118), ApoB, IgJH, D4S95]. RESULTS: We found that one of the fetuses was heterozygous for SCA and the other was normal in family A; in family B both fetuses were heterozygous and in family C both fetuses were normal. CONCLUSION: Prenatal diagnosis is the major way of prevention of the genetic disorders including sickle cell anemia. Prenatal diagnosis of twins contains additional risks such as confusion in differentiation leading to false molecular diagnosis. VNTR loci analysis is a useful tool and can be safely used for the elimination of all problems mentioned above.

IRS-2 G1057D polymorphism in Turkish patients with colorectal cancer.

INTRODUCTION: Gene polymorphisms have a broad range of analysis, but are of particular use in molecular medicine due to their potential in revealing the genetic tendency in diseases such as cancer, heart attack etc. These studies basically depend on mutations that can be detected by proper techniques. The genes coding the insulin receptor substrate (IRS) proteins are among the most widely analysed polymorphisms in various cancer types, in which a G1057D mutation is seen. AIM: To determine the risk of colon cancer by analysing the IRS-2 gene polymorphism in Turkish patients. MATERIAL AND METHODS: A total of 161 newly diagnosed colorectal cancer patients were analysed and compared to 197 unrelated healthy controls. A polymerase chain reaction-based restriction fragment length polymorphism method was carried out. RESULTS: No differences were observed between the patient and control groups for both allele and genotype frequencies of the IRS-2 G1057D gene. CONCLUSIONS: Our results demonstrated that IRS-2 G1057D polymorphism is not associated with colorectal cancer in the Turkish population. This research is a preliminary and original study in Turkish patients with colorectal cancer. It also provides population-level genetic data on IRS-2 in the Turkish population. Further studies should be performed on larger number of patients and controls for more reliable results about the genetic tendency in colorectal cancer in Turkey. The study is a collaborative work of different universities and scientists.

The association between cyclooxygenase-2 (COX-2/PTGS2) gene polymorphism and osteoarthritis.

OBJECTIVES: This study aims to investigate the relationship between the risk for the development of osteoarthritis and Cyclooxygenase-2 (COX 2) -765G>C gene polymorphism. PATIENTS AND METHODS: We included a total of 100 osteoarthritis patients (18 males, 82 females; mean age 60.4±8.4 years; range 41 to 81 years) who were treated in the Physical Therapy Clinic and 100 healthy subjects without a history of arthritis (40 males, 60 females; mean age 30.9±7.5 years; range 16 to 48 years) in our study between September 2006 and May 2008. The frequency of -765G>C gene polymorphism in the COX-2 promoter region was investigated in the osteoarthritis patients and the control group without a history of arthritis using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analysed with chi-square and logistic regression analysis. RESULTS: The frequencies of -765G>C polymorphism for GG, GC and CC genotypes were found to be 54%, 35%, and 11% in the control group and 48%, 34% and 18% in the osteoarthritis group, respectively. CONCLUSION: Based on the data obtained, it can be stated that there is no significant relation between COX-2 -765G>C polymorphism and osteoarthritis disease. Furthermore, this study presents the first results of COX-2 promoter variant in Turkish patients with osteoarthritis.

Allele frequency distributions of Apo B VNTR locus in Cukurova, Turkey.

The highly polymorphic minisatellites contain a variable number of tandemly repeated (VNTR) DNA sequences. They are extremely useful and informative markers to study genetic variation among human populations. We have analysed the allele frequency distribution at the highly polymorphic apolipoprotein B (Apo B) VNTR locus in order to obtain the population data for the Cukurova region in Turkey by using the polymerase chain reaction and polyacrylamide gel electrophoresis. We observed 10 different alleles and 21 genotypes in a sample of 100 unrelated individuals. The allele frequencies ranged from 0.01 to 0.4, with an expected heterozygosity of 0.69 for the Apo B locus. Alleles 37 (frequency = 0.4) and 35 (frequency = 0.17) were the most common in the Cukurova population. There was a significant deviation from the Hardy-Weinberg equilibrium (HWE) for genotype frequencies (chi2 = 29.12; df = 1; p = 0.000). This study possesses novelty as it is the first DNA polymorphism study conducted at the Cukurova population using an Apo B minisatellite locus.