Germline Mutations in PALB2, BRCA1, and RAD51C, Which Regulate DNA Recombination Repair, in Patients With Gastric Cancer.

Up to 10% of cases of gastric cancer are familial, but so far, only mutations in CDH1 have been associated with gastric cancer risk. To identify genetic variants that affect risk for gastric cancer, we collected blood samples from 28 patients with hereditary diffuse gastric cancer (HDGC) not associated with mutations in CDH1 and performed whole-exome sequence analysis. We then analyzed sequences of candidate genes in 333 independent HDGC and non-HDGC cases. We identified 11 cases with mutations in PALB2, BRCA1, or RAD51C genes, which regulate homologous DNA recombination. We found these mutations in 2 of 31 patients with HDGC (6.5%) and 9 of 331 patients with sporadic gastric cancer (2.8%). Most of these mutations had been previously associated with other types of tumors and partially co-segregated with gastric cancer in our study. Tumors that developed in patients with these mutations had a mutation signature associated with somatic homologous recombination deficiency. Our findings indicate that defects in homologous recombination increase risk for gastric cancer.

Evaluation of BRCA2 in the genetic susceptibility of familial esophageal cancer.

Previous studies of esophageal squamous cell carcinoma (ESCC) have shown a high frequency of allelic loss on chromosome 13q, infrequent somatic mutations in BRCA2, and a suggested association between a positive family history (FH+) of upper gastrointestinal cancer and germline BRCA2 mutations. In all, 70 ESCC patients (44 FH+ and 26 FH-) were examined by direct full sequencing of germline DNA for BRCA2 mutations. In addition, 28 family members of three of these patients and 232 unrelated healthy blood bank donor controls were examined for the mutations identified in the 70 ESCC patients. Five BRCA2 germline mutations, including three not previously reported (N1600del, A2054P, and V2109I), were identified in six of 44 FH+ patients, but none of 26 FH- patients (14 vs 0%, P=0.078), consistent with our previous findings (3/34 or 9% FH+ vs 0/22 or 0% FH-, P=0.27). The cumulative frequency of BRCA2 germline mutations in ESCC patients in this and our previous study combined is 12%, with all mutations found in FH+ as opposed to FH- cases (9/78 or 12% FH+ vs 0/48 or 0% FH-, P=0.013). We conclude that germline mutations in BRCA2 in ESCC patients from this high-risk area of China are more frequent in FH+ than FH- cases, suggesting that BRCA2 may play a role in genetic susceptibility to familial ESCC.

Finding new sources from "using different plants as the same herb": A case study of Huang-lian in Northwest Yunnan, China.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional and local medicinal knowledge would be useful for finding pharmaceutical resources. Ethnopharmacological methods, especially quantitative analysis could help us to pre-screen herbs in field studies. "Using different plants as the same herb" is common in both traditional and local medicinal systems in China. In terms of medicine safety, it is not best choice, for it would lead to difficulty in controlling the quality, safety and efficacy of herbs. However, from the perspective of finding new resources for pharmaceutical industry, it would be beneficial. The usage of Huang-lian is one of the typical examples of "using different plants as the same herb". According to the previous Phytochemical and Pharmacological studies, berberine is the common effective compound of most of the species used as Huang-lian. Recently, berberine and other effective compounds of Huang-lian have gained much more attention and will become more popular in both medicinal researches and pharmaceutical industry. In our preliminary field work, we found that dozens of plant species might be used as Huang-lian by local people in Northwest Yunnan, an area well known by its rich biodiversity and culture diversity. These herbs might have potential value for pharmaceutical industry, for example, it could be used as the new resources to extract berberine and other effective compounds. Due to this, it is very necessary to collect, identify, document, and analyze the herbs used as Huang-lian in NW Yunnan. In the present study, we focused on that how to use traditional and local medicinal knowledge to find resources for pharmaceutical industry. MATERIAL AND METHODS: In the field work, interviews and participative observation were used. In the quantitative analysis of the local knowledge, Informant consensus factor (Fic), Use value (UV) and Relative frequency of citation (RFC) were used. RESULTS AND DISCUSSION: A total of 230 key informants were interviewed and 29 plant species belonging to 8 families and 11 genera used as Huang-lian were collected in the study area. Diarrhoea had the highest value of Fic.xiana had the highest value of UV and RFC. The main effective compounds of most of these species were related to the protoberberine group of isoquinoline alkaloids, e.g. berberine, jatrorrhizin and palmatine, according to the previous phytochemical studies. CONCLUSION: The range of sources of Huang-lian were very wide in NW Yunnan. Treating diarrhoea was the most common use of these species, most of which contained berberine. Based on the results of quantitative analysis, M. duclouxiana may had the greatest potential to future uses, e.g. as a resource for pharmaceutical industry. In the present study, we did not discuss whether the herbs used as Huang-lian could replace the standard Huang-lian in traditional or local medicine or not, and we just wanted to explore how this phenomenon could be used to find new resources for pharmaceutical industry.

[Evaluation on the visual inspection with Lugol's iodine in cervical cancer screening program].

OBJECTIVE: To evaluate visual inspection with Lugol's iodine (VILI) in cervical cancer screening program and to provide evidence for designing a cervical cancer screening algorithm in high risk areas of existing low-resource settings to reduce the incidence and mortality of cervical cancer. METHODS: Women in Yangcheng county, Shanxi province were screened with VILI, colposcopy, liquid-based cytology test and human papilloma virus (HPV) DNA test. The efficacy of different screening tests was compared by Youden's index based on the pathology as the gold standard. RESULTS: In the population being screened, the mean age was 40.80 +/- 10.75 years old. Based on pathological findings, 4.35% (32/735) of the subjects had >or= CIN (cervical intraepithelial neoplasia) II. The sensitivity and specificity for the VILI test (>or= positive) were 53.13 and 82.19, while 56.25 and 79.09 were for colposcopy (>or= low grade dysplasia) respectively. Comparing by the Youden's indexs, there was no statistically significant difference (P > 0.05) between VILI and colposcopy. However, statistical significant difference (P < 0.05) was found between VILI and liquid-based cytology test and HPV DNA test. In addition, there was no statistically significant difference (P > 0.05) found between the experienced doctors and the newly-trained doctors working in the field station. CONCLUSION: With low sensitivity when using microscope but low cost of equipments, VILI can be one of the primary screening tests in China's rural area with low-resource settings if the screening frequency is to be increased.

Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China.

TP53 and BRCA2 are frequently mutated in cancer and polymorphisms of these genes may modify cancer risk. We used SSCP and DNA sequencing to assess and compare frequencies of R72P (TP53) and 5'UTR203G>A, N372H, and K1132K (BRCA2) polymorphisms in healthy Chinese subjects at varying risk for esophageal squamous cell carcinoma (ESCC) and in ESCC patients. Suggestive overall differences in the distributions of genotypes by risk groups were seen for all genotypes except K1132K. Differences in R72P and N372H were most likely a reflection of lack of Hardy-Weinberg equilibrium (HWE), however, the difference in 203G>A was due to low prevalence of GG in ESCC patients (0.22 versus 0.36 in high risk group (P=0.047), and 0.22 versus 0.40 in low risk group (P=0.010)), consistent with a disease association. These data suggest that the 203G>A polymorphism in BRCA2 may be associated with risk of ESCC.