Purpose:To estimate prevalence of BRCA1 and BRCA2 mutations among Chinese patients with breast cancer in eastern China. Methods:Frozen tumor tissues were obtained from 79 female patients, and three exons (2, 11, 22) of BRCA1 and three exons (9, 14, 22) of BRCA2 were examined with 23 pairs of primer, using polymerase chain reaction (PCR) single strand conformational polymorphism (SSCP) sequencing method. Results:It was found that in cDNA of BRCA1, there is a single nucleotide variation of T→C at position of 2430. By the RFLP method, we confirmed that the variation in the general population is a single nucleotide polymorphism. The distribution of T allele and C allele is different between cases and controls, but the difference is not significant. Conclusions:It implied that the mutations of BRCA1 and BRCA2 in breast cancer patients in eastern China is very rare.

Objective To make sure whether there is any association between genetic polymorphism of tumor necrosis factor (TNF) ? and systemic lupus erythematosus (SLE).Method PCR RFLP was used.A population based and family based study was carried out in 99 SLE patients,116 health controls and 12 families.Results The TNF ?2 allele frequency of SLE patients was significantly different from that of controls ( P

OBJECTIVETo study the genetic polymorphisms of UDP-glucuronosyltransferase 1F(UGT1F) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC).

METHODSThe polymorphisms of UGT1F of 84 patients with HCC and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing.

RESULTSThree new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of UGT1F in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant.

CONCLUSIONExons 2-5 of UGT1F are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with HCC.

Alleles ; Amino Acid Substitution ; Base Sequence ; Carcinoma, Hepatocellular ; enzymology ; genetics ; DNA Mutational Analysis ; DNA, Neoplasm ; chemistry ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glucuronosyltransferase ; genetics ; Humans ; Liver Neoplasms ; enzymology ; genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational

OBJECTIVETo explore the interaction between inheritance and environment with the aid of research on the genetic modes of hepatocellular carcinoma (HCC).

METHODSA genetic epidemiological study of HCC was conducted based on the methods of Penrose, simple segregation and Falconer for 100 proband pedigrees from HBsAg positive cohort. The proband samples came from a cohort of 90,00 people who were followed for 8 years. Analyses on genetic modes were carried out and heritability was calculated through the comparison of the proband pedigrees incidence frequency with incidence frequencies of the cohort and general population.

RESULTSThe incidence frequency of first-degree relatives was 4.0%, higher than what was seen in the general population incidence frequency (0.44%) and the cohort (1.03%). A familial aggregation of HBsAg carriers and a strong positive correlation between HBsAg carrier status and HCC were noticed (OR = 8.44, 95% CI: 3.37-20.06, P < 0.001). A ratio of the incidence frequency among siblings to the incident frequency among general population (s/q) approached 1/q(1/2) by Penrose method, but simple segregation did not show agreement with single-gene inheritance. The heritability from positive cohort was 42% +/- 6% (P < 0.05), compared with the heritability (59% +/- 7%) of general population. When the effect of the HBsAg was under control, the heritability from positive cohort turned to be 29% +/- 8% (P < 0.05), compared with the heritability (47% +/- 7%) of general population.

CONCLUSIONOur findings suggested that HCC followed a multifactorial mode rather than single inheritance. An interaction effect of inheritance and environment on HCC was also noticed.

Carcinoma, Hepatocellular ; epidemiology ; genetics ; China ; epidemiology ; Environment ; Female ; Hepatitis B Surface Antigens ; analysis ; Humans ; Incidence ; Liver Neoplasms ; epidemiology ; genetics ; Male

OBJECTIVETo identify risk factors for gestational diabetes mellitus (GDM) in women and to study the contribution of family history of type-2 diabetes to the risk for DDM.

METHODSA case-control study was performed in 85 women with GDM and 177 cases controls. Univariate and multivariate logistic regression and log-linear model were used to identify risk factors of GDM.

RESULTSMultivariate logistic regression showed that obesity before pregnancy, family history of type-2 diabetes, birth weight of pregnant women, age, fasting plasma level of triglyceride, physical inactivity, etc. all were risk factors for GDM. Analysis with log-linear model showed that parents' (father's or mother's) history of type-2 diabetes associated with GDM, with P-values of 0.012 and 0.017, respectively. Prevalence of diabetes in the mothers of proband with GDM was 9.41%, as compared with that in the fathers of proband with GDM 8.24%, with no statistical significance.

CONCLUSIONSObesity before gestation, family history of type-2 diabetes, low birth weight of mother, age, increased fasting plasma level of triglyceride, as well as parents' history of type-2 diabetes, all were risk factors for GDM. Physical exercise was found to be a protective factor for GDM. Mother's history of type-2 diabetes did not differ from father's in contributing to the onset of GDM in their offspring.

Adult ; Birth Weight ; Diabetes Mellitus ; genetics ; Diabetes, Gestational ; etiology ; Exercise ; Female ; Humans ; Logistic Models ; Obesity ; complications ; Pregnancy ; Risk Factors ; Triglycerides ; blood

Objective: To investigate the incidence, molecular features and clinical significance of RNA splicing machinery genes mutation in myelodysplastic syndromes (MDS) and related diseases. Methods: Mutational analysis of splicing factor 3B subunit 1 (SF3B1) (K700E) , U2 small nuclear RNA auxiliary factor 1 (U2AF1) (S34, Q157P) and serine/arginine-rich splicing factor 2 (SRSF2) (P95) in 118, de novo MDS and related diseases were separately performed by using polymerase chain reaction (PCR) followed by sequence analysis. Results: Of 118 MDS patients, 76 males and 42 females, the median age was 53.5 (13-84) years old. 19.49% (23/118) had SF3B1 (K700E) mutation. As compared with those with wild type SF3B1, patients with SF3B1 K700E were of older[58 (32-78) years vs 51 (13-84) years, z=-1.981, P=0.048], lower HGB level[63 (40-95) g/L vs 77 (34-144) g/L, z=-3.192, P=0.001], higher platelet counts[121 (22-888) ×10⁹/L vs 59 (6-1 561) ×10⁹/L, z=-3.305, P=0.001], lower bone marrow blast cell counts[0.007 (0-0.122) vs 0.017 (0-0.268) , z=-2.885, P=0.004], higher ring sideroblasts percent [0 (0-64%) vs 0 (0-58%) , z=-4.664, P<0.001]. Of 105 MDS patients, 21.9% had U2AF1 (S34, Q157P) mutations. Of 107 MDS patients, 8 patients (7.48%) had SRSF2 (P95) mutations. Patients with SRSF2 mutations were older at diagnosis, the median age was 63 (50-84) years old, including 4 cases RAEB-1. The ratio of mutation was 14.29% (4/28) , and three patients transformed to AML. SF3B1 K700E and SRSF2 P95H mutations coexisted in 1 patient, and SF3B1 K700E and U2AF1 S34Y mutations were found concomitantly in 2 patients. Conclusion Only SF3B1 gene mutation was closely related to ring sideroblasts, it was the key to pathogenesis of MDS.