Evaluation and integration of genetic signature for prediction risk of nasopharyngeal carcinoma in Southern China.

Unlabelled: Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted.

The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62) = 7.

HTLV-2B strains, similar to those found in several Amerindian tribes, are endemic in central African Bakola Pygmies.

Background: The presence and origin of endemic foci of human T-lymphotropic virus type 2 (HTLV2) infection in Africa remain a matter of debate.

Methods: To better appreciate such determinants, we performed a survey of 1918 inhabitants from Cameroon forest areas, including 1051 Bakola Pygmies and 867 Bantus.

Results: The overall HTLV-1/2 seroprevalence was 4% (49 cases of HTLV-1 and 27 cases of HTLV-2 infection).

Geographic heterogeneity of prevalence of the human herpesvirus 8 in sub-Saharan Africa: clues about etiology.

Purpose: Human herpesvirus 8 (HHV-8, or Kaposi sarcoma [KS]-associated herpesvirus, KSHV) is a necessary but insufficient cause of KS, as KS develops in few HHV-8-infected persons. In sub-Saharan Africa, marked differences in the geographic distribution of HHV-8 and KS suggest that environmental cofactors influence HHV-8 transmission, control, and progression to KS. However, a direct comparison of HHV-8 prevalence estimates is complicated because studies used different serologic assays and analytic methods.

An estimate of cancers attributable to occupational exposures in France.

Objective: To perform a quantitative estimate of the proportion of cancers attributable to occupational exposures in France in 2000.

Methods: Exposure data for established carcinogens were obtained from a 1994 survey and other sources. Relative risks for 23 exposure-cancer combinations were derived from meta-analyses and pooled analyses.

Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China.

To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n = 1,049) were compared with 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)-a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data.

Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: study design, methods and feasibility.

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals.

[Association study of chromosome 4 STRs polymorphisms with nasopharyngeal carcinoma].

Nasopharyngeal carcinoma (NPC) is a complex disease caused by an interaction of EBV chronic infection, environment and host genes, in a multi-step process of carcinogenesis. However, which genetic factors play an important role in the development of chronic EBV infection and NPC remain elusive. The objective of this study is to identify genetic variations associated with two key clinical stages of NPC development: persistent Epstein-Barr virus (EBV) infection of nasopharyngeal epithelia and progression to NPC.

Chimeric peptide vaccine composed of B- and T-cell epitopes of human T-cell leukemia virus type 1 induces humoral and cellular immune responses and reduces the proviral load in immunized squirrel monkeys (Saimiri sciureus).

A squirrel monkey model of human T-cell leukemia virus type 1 (HTLV-1) infection was used to evaluate the immunogenicity and protective efficacy of a chimeric peptide vaccine composed of a B-cell epitope from the envelope region (aa 175-218) and three HLA-A*0201-restricted cytotoxic T-lymphocyte epitopes derived from Tax protein (Tri-Tax). These selected Tax peptides induced secretion of gamma interferon (IFN-gamma) in peripheral blood mononuclear cells obtained from monkeys chronically infected with HTLV-1. After immunization, a high titre of antibodies and a high frequency of IFN-gamma-producing cells were detected against the Env and the Tri-Tax immunogens, but not against the individual Tax peptides.

Searching for signals of evolutionary selection in 168 genes related to immune function.

Pathogens have played a substantial role in human evolution, with past infections shaping genetic variation at loci influencing immune function. We selected 168 genes known to be involved in the immune response, genotyped common single nucleotide polymorphisms across each gene in three population samples (CEPH Europeans from Utah, Han Chinese from Guangxi, and Yoruba Nigerians from Southwest Nigeria) and searched for evidence of selection based on four tests for non-neutral evolution: minor allele frequency (MAF), derived allele frequency (DAF), Fst versus heterozygosity and extended haplotype homozygosity (EHH). Six of the 168 genes show some evidence for non-neutral evolution in this initial screen, with two showing similar signals in independent data from the International HapMap Project.

Mother-child health research (IRN-MCH): achievements and prospects of an international network.

The Inter-Academy Panel (IAP) is critical about the scarce support to mother-child health (MCH) research in developing countries. At the request of the IAP, a group of members of the French and Swedish Academies of Science have arrived at the conclusion that an efficient network between scientists in resource-poor and industrialized countries will facilitate MCH research in developing countries. The priorities for such a network have been listed as follows: The present organization for the MCH website at the Pasteur Institute in Paris should be adapted to better promote collaboration between scientists from industrialized and developing countries.

The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern.

The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping.

A high-density admixture map for disease gene discovery in african americans.

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples.