OBJECTIVETo study the distribution of IL-10 gene polymorphisms in patients with gastroduodenal diseases in Hubei Han population and their association with helicobacter pylori (Hp) infection.

METHODSSix hundred and five patients with gastroduodenal diseases (220 gastric cancer, 196 chronic gastritis and 189 gastroduodenal ulcer) and 624 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for IL-10 -1082, -819, -592 gene polymorphisms. Hp infection status was determined by ELISA.

RESULTS(1) There was significant difference of IL-10 -1082 AG+GG genotypes between gastric cancer group and gastric cancer-free and healthy control groups (P<0.05). (2) There was no significant difference of IL-10 -592 and IL-10 -819 gene polymorphisms among gastric cancer, gastric cancer-free and healthy control groups (P>0.05). (3) The frequency of IL-10 -1082 AG+GG genotypes in the Hp positive gastric cancer patients was significantly higher than that of control groups (P<0.05).

CONCLUSIONS(1) Genotypes AG+GG of IL-10 -1082 were associated with gastric cancer in Hubei Han population. (2) The IL-10 -1082 AG+GG genotypes were associated with Hp infection in patients with gastric cancer.

Adult ; Aged ; Case-Control Studies ; China ; ethnology ; Duodenal Diseases ; ethnology ; genetics ; microbiology ; Female ; Genetic Association Studies ; Genotype ; Helicobacter Infections ; ethnology ; genetics ; microbiology ; Humans ; Interleukin-10 ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Stomach Neoplasms ; ethnology ; genetics ; microbiology

The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modern day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome combinations, or haplotypes (e.g. HLA-A2-B46), whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently, a strength of association reflecting the 30-50-fold difference in incidence between highest risk Cantonese and lowest-risk Indians. The prototypic haplotype HLA-A2-B46 extends over megabases. An upstream DNA segment (near HLA-DPA1), has close similarity to Gorilla, with no obvious homology to Chimpanzee in current databases, suggesting that a reticulate model of primate evolution may be more appropriate than simple phylogeny. The DNA variation level in this segment is high enough for it to be a hominin remnant. HLA-B46 arose in mongoloids and remains largely limited to Chinese so the question arises as to whether the hominin candidate segment indicates an eastward trek of Homo neanderthalensis or the survival of much earlier Homo erectus? In 2011 sequencing technologies have finally caught up with the requirement to separate parental haplotypes. Recently achieved chromosome separation for whole genome di-haploid genetic and epigenetic analysis of parental inheritance in single individuals will reveal interacting patterns of multi-locus haplotypes as humans move in and through successive environments, thus providing definitive information on the genetic affinities between extant populations, and of the migrations that have led to the global distribution of modern Homo. The challenge can now be met of seeking HLA-associated locations both within and outside the HLA complex on each of the pair of chromosomes. More broadly, for every disease, genetic risk detection will require resolution of the diploid genome as a di-haplome. In the context of NPC, HLA genetic risk complete autosomal di-haplomic sequencing will enable testing of the Wee unitary origin hypothesis of NPC risk even among populations with no apparent mongoloid affinity.
China ; epidemiology ; Emigration and Immigration ; Genetics, Population ; Herpesvirus 4, Human ; immunology ; Humans ; Nasopharyngeal Neoplasms ; ethnology ; genetics ; immunology

Long-lived people may have a unique genetic makeup that makes them more resistant than the general population to prevalent age-related diseases; however, not much is known about genes involved in the longevity. To identify susceptibility variants controlling longevity, we performed a high-throughput candidate gene study using 137 Koreans over 90 yr old and 213 young healthy Koreans. We evaluated 463 informative markers located in 176 candidate genes mostly for diabetes mellitus, cardiovascular disease and cancer under five genetic models. We estimated the odds ratios for each allele, genotype, haplotype, and gene-gene interaction using logistic regression analysis. Associations between 13 genes and longevity were detected at a P-value less than 0.01. Particularly, the rs671 (A) allele of the aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) gene was associated with longevity only in men (OR 2.11, P = 0.008). Four genes, proprotein convertase subtilisin/kexin type 1 (PCSK1, P = 0.008), epidermal growth factor receptor (EGFR, P = 0.003), paired box 4 (PAX4, P = 0.008), and V-yes-1 Yamaguchi sarcoma viral related oncogene homolog (LYN, P = 0.002) consistently yielded statistical evidence for association with longevity. The findings of the current study may provide a starting point for future studies to unravel genetic factors controlling longevity in Koreans.
Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase/genetics ; Alleles ; Asian Continental Ancestry Group/ethnology/genetics ; Cardiovascular Diseases/ethnology/*genetics ; Diabetes Mellitus/ethnology/*genetics ; Female ; Genetic Markers/genetics ; Haplotypes ; Homeodomain Proteins/genetics ; Humans ; Korea ; Longevity/*genetics ; Male ; Middle Aged ; Neoplasms/ethnology/*genetics ; Paired Box Transcription Factors/genetics ; *Polymorphism, Genetic ; Proprotein Convertase 1/genetics ; Receptor, Epidermal Growth Factor/genetics ; Sex Factors ; src-Family Kinases/genetics

OBJECTIVETo study the distribution of HLA-DRB1 allele polymorphism in Uyghur women with family history of cervical cancer, and provide theoretical evidence for detection and follow-up of high risk persons for cervical cancer by detection of HLA-DRB1 allele polymorphism.

METHODSThe HLA-DRB1 13 alleles were detected in 1000 Uyghur women, all from Hotan Moyu county Karsay village by using polymerase chain reaction sequence-specific oligonucleotide (PCR-SSO) assay.

RESULTSThe frequencies of HLA-DRB1*15 in women with family history of cervical cancer (17.3%), mother (18.0%) and other relatives except mother (17.0%) who had suffered from cervical cancer were significantly higher than that in the control group (9.7%, all P < 0.05). The frequencies of HLA-DRB1*04 in women with family history (16.8%) and other relatives except mother (20.7%) were significantly higher than that in the control group (12.7%, all P < 0.05). The frequencies of HLA-DRB1*03 in women with family history (2.6%) and other relatives except mother (1.1%) were significantly lower than that in the control group (6.3%, all P < 0.01). The frequencies of HLA-DRB1*12 in women with family history of cervical cancer (2.3%) and mother suffered from cervical cancer (1.5%) were significantly lower than that in the control group (5.7%, all P < 0.05). The frequencies of HLA-DRB1*14 in women with family history of cervical cancer (5.4%) and mother who suffered from cervical cancer (3.0%) were significantly lower than that in the control group (8.4%, all P < 0.05).

CONCLUSIONSThere are similarity and difference in distribution of HLA-DRB1 allele polymorphisms between the Uyghur women with family history of cervical cancer from Hotan Moyu county and those from southern Xingjiang area. In general, the distribution of HLA-DRB1 allele polymorphism in women with family history of cervical cancer is similar to that reported in abroad. The results of this study support the role of susceptible and protective HLA gene detection in screening high risk persons for this cancer among Uyghur women from cervical cancer high risk areas in Xinjiang.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; HLA-DRB1 Chains ; genetics ; Humans ; Polymorphism, Genetic ; Uterine Cervical Neoplasms ; genetics ; immunology

OBJECTIVETo explore the relationship between human papillomavirus(HPV) infection and expression of human leukocyte antigen class I (HLA-I) family genes (HLA-A, B and C) in cervical cancers of Uighur women, and to investigate their effect on cervical cancer progression.

METHODSFresh tissue samples of 78 Uighur women with cervical squamous carcinoma, cervical intraepithelial neoplasia (CIN) or benign cervicitis were selected. HLA-A, B and C expression and HPV infection were analyzed using RT-PCR and HPV gene chips, respectively.

RESULTSThere was a tendency of increasing the total loss of HLA-A, B and C mRNA as the cervical lesions became more aggressive. Loss of HLA-I mRNA in CIN (I, II and III) and cervical squamous carcinoma was 70.0% (14/20) and 84.8% (39/46) respectively. Poorly differentiated cervical carcinomas had the highest HLA-I expression loss (90.6%). In contrast, HLA-I mRNA loss was seen in only 8% of cases of cervicitis. Moreover, it was found that high risk HPV 16 infection was strongly correlated with the loss HLA-I mRNA expression (r = 0.803, P < 0.01).

CONCLUSIONSThe loss of HLA-I gene expression is strongly correlated with HPV-16 infection, and may serve as a biomarker of cervical cancer progression in Uighur women.

Adult ; Aged ; Carcinoma, Squamous Cell ; ethnology ; genetics ; immunology ; virology ; Cervical Intraepithelial Neoplasia ; ethnology ; genetics ; immunology ; virology ; China ; ethnology ; Female ; HLA Antigens ; genetics ; metabolism ; HLA-A Antigens ; genetics ; metabolism ; HLA-B Antigens ; genetics ; metabolism ; HLA-C Antigens ; genetics ; metabolism ; Human papillomavirus 16 ; isolation & purification ; Humans ; Middle Aged ; Papillomavirus Infections ; ethnology ; genetics ; immunology ; virology ; RNA, Messenger ; metabolism ; Uterine Cervical Neoplasms ; ethnology ; genetics ; immunology ; virology ; Uterine Cervicitis ; ethnology ; genetics ; immunology ; virology

OBJECTIVETo investigate the association between the polymorphism of CYP17 gene and risk of prostate cancer in Chinese Vigurs men.

METHODSA case-control study including 31 patients with prostate cancer and 104 aged-matched controls was conducted. The polymorphism was investigated by PCR using DNA from peripheral blood lymphocytes. The transition (T-->C) in the risk allele (A2) produced a new recognition site for the restriction enzyme MSPAI I. Three genotypes of CYP17 gene (A1/A1, A1/A2, A2/A2) were determined and confirmed by sequencing.

RESULTSCompared with male A1/A1 genotype, the odds ratios were 1.49 and 2.87 for the A1/A2 and A2/A2 genotypes (P =0.321, 0. 052, respectively). Comparison among 3 subgroups (division by genetypes) of prostate cancer patients, the PSA levels were not significantly different. But in the controls, PSA levels in A1/A2 group were higher but not significant than those in A1/A1 group (P = 0.062). Then, PSA levels in A2/A2 group were significantly higher than those A1/ A1 group (P = 0.018).

CONCLUSIONMore frequency of A2/A2 genotype in prostate cancer than in the control may be associated with the morbidity of prostate cancer in Vigurs male population. Meanwhile, the significant high PSA levels in A2/A2 group also support the view.

Aged ; Aged, 80 and over ; Case-Control Studies ; China ; ethnology ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prostatic Neoplasms ; ethnology ; genetics ; Steroid 17-alpha-Hydroxylase ; genetics

OBJECTIVEArylamine N-acetyltransferases (NATs) are involved in the detoxification of aromatic amines and hydrazine. In order to explore the possible association of NAT2 polymorphism with bladder cancer risk in benzidine exposed or non-exposed Chinese individuals, healthy subjects, subjects with bladder cancer of a former benzidine exposed cohort in Shanghai dyestuff industry and a group of bladder cancer patients without known occupational exposure to aromatic amines were genotyped for NAT2 gene polymorphism.

METHODSNAT2 genotyping was performed with a set of RFLP procedures at seven major polymorphic loci of gene coding area: G191A, C282T, T341C, C481T, G590A, A803G and G857A.

RESULTSThe wild allele NAT2 *4 was the most prevalent allele (59%) in healthy individuals. The alleles NAT2*6A and NAT2*7B were also frequently observed (21% and 17%, respectively). In contrast to Caucasians, the percentage of slow acetylators was lower (12% in Chinese vs. 58% in Caucasians, P < 0.001). No relevant differences were observed for homogenous rapid, heterogeneous rapid/slow and homogeneous slow acetylation genotypes between the healthy subjects and both groups of bladder cancer patients.

CONCLUSIONThe present work did not support the association of slow acetylating genotypes of NAT2 gene with elevated risk of bladder cancer in Chinese whereas it was documented as an important genetically determined risk factor in Caucasians. Different mechanisms might play a role in individual susceptibility to bladder cancer related with aromatic amine exposure in various races or ethnic groups.

Arylamine N-Acetyltransferase ; genetics ; Asian Continental Ancestry Group ; Benzidines ; toxicity ; Case-Control Studies ; Chemical Industry ; China ; epidemiology ; ethnology ; Coloring Agents ; Genetic Predisposition to Disease ; Genotype ; Humans ; Occupational Diseases ; epidemiology ; ethnology ; genetics ; Occupational Exposure ; Polymorphism, Genetic ; Urinary Bladder Neoplasms ; epidemiology ; ethnology ; genetics

Asian Continental Ancestry Group ; genetics ; Ethnic Groups ; genetics ; Female ; Genetics, Population ; Humans ; Male ; Nasopharyngeal Neoplasms ; epidemiology ; ethnology

OBJECTIVETo investigate the association of p53 codon 72 polymorphism with susceptibility to esophageal cancer and lung cancer in the northern Chinese population.

METHODSp53 codon 72 genotyping was performed by amplifying DNA fragments with sequence specific primers among 173 patients with esophageal squamous cell carcinoma, 98 with non-small cell lung carcinoma as well as 136 healthy controls.

RESULTSNo significant difference of p53 allelotype and genotype distribution was observed between esophageal cancer and lung cancer patients. The Pro allele frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.024 and 0.027 respectively). There were no significant differences in Pro/Arg and Arg/Arg genotype frequency among cancer patients and healthy controls (P > 0.05). However, the Pro/Pro genotype frequency was significantly higher among esophageal cancer and lung cancer patients than among healthy controls (P value was 0.041 and 0.026 respectively). The risk of Pro homozygotes for both esophageal cancer and lung cancer was about 2 times against Arg homozygotes with adjusted odds ratio of 2.12 (95% CI = 1.13 - 4.01) and 2.30 (95% CI = 1.13 - 4.93), respectively. There was no interaction between p53 Pro/Pro genotype and smoking status to the risk for esophageal cancer and lung cancer.

CONCLUSIONIn the northern Chinese population, p53 Pro/Pro genotype is an independent risk factor for both esophageal cancer and lung cancer. The possible common genetic basis of the development of these two cancers is suggested by this study.

Alleles ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung ; ethnology ; genetics ; Carcinoma, Squamous Cell ; ethnology ; genetics ; China ; Codon ; genetics ; Esophageal Neoplasms ; ethnology ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lung Neoplasms ; ethnology ; genetics ; Odds Ratio ; Polymorphism, Genetic ; Tumor Suppressor Protein p53 ; genetics

OBJECTIVETo investigate the relationship between p53 codon 72 polymorphism and susceptibility to esophageal squamous cell carcinoma in China.

METHODSThe p53 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism among 204 healthy controls and 91 patients with esophageal squamous cell carcinoma (ESCC).

RESULTSThere was no significant difference between patients and controls with respect to allele frequency for the p53 Pro allele (0.480 versus 0.588, P=0.11); however, the Pro/Pro genotype of p53 among cases (39.6%) was significantly (P<0.05) more frequent than that among controls (21.1%). Subjects homozygous for the p53 Pro allele had a more than 2-fold increased risk of developing ESCC (OR=2.18; 95%CI=1.10-4.35, adjusted for age, sex, and smoking), whereas the Arg/Pro genotype was not associated with elevated risk of the cancer (adjusted OR=0.84; 95%CI=0.42-1.68). No interaction between smoking and Pro/Pro genotype was observed for risk of ESCC.

CONCLUSIONThe p53 codon 72 polymorphism may play a role in susceptibility to esophageal carcinogenesis.

Alleles ; Arginine ; genetics ; Asian Continental Ancestry Group ; genetics ; Carcinoma, Squamous Cell ; ethnology ; genetics ; Codon ; genetics ; Confidence Intervals ; Esophageal Neoplasms ; ethnology ; genetics ; Genetic Predisposition to Disease ; Genotype ; Humans ; Odds Ratio ; Polymorphism, Genetic ; Proline ; genetics ; Tumor Suppressor Protein p53 ; genetics