Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas ...(NPCs) and 10 normal healthy nasopharyngeal epithelial samples. In particular, miRNA mir-29c was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower mir-29c levels correlated with higher levels of multiple mRNAs whose 3' UTRs can bind mir-29c at target sequences conserved across many vertebrates. In cultured cells, introduction of mir-29c down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3' UTRs of these genes. Moreover, for each of several genes tested, mutating the mir-29c target sites in the 3' UTR abrogated mir-29c-induced inhibition of luciferase expression. Most of the mir-29c-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin γ1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis.
A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan.
A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, ...and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (OR(adj)) with 95% confidence interval (CI) after accounting for known risk factors.
Fresh fish (OR(adj), 0.56; 95% CI, 0.38-0.83 for the highest vs. lowest tertile of intake), green tea (OR(adj), 0.61; 95% CI, 0.40-0.91 for drinking ≥1 times/week vs. never) and coffee (OR(adj), 0.56; 95% CI, 0.37-0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (OR(adj), 0.62; 95% CI, 0.41-0.94 for the highest vs. lowest tertile).
The study findings suggest that certain adult dietary patterns might protect against the development of NPC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The association between human leukocyte antigen (HLA) genes (located in the Major Histocompatibility Complex MHC region of chromosome 6p21) and NPC has been known for some time. Recently, two ...genome-wide association studies (GWAS) conducted in Taiwan and China confirmed that the strongest evidence for NPC association was mapped to the MHC region. It is still unclear, however, whether these findings reflect direct associations with Human Leukocyte Antigen (HLA) genes and/or to other genes in this gene-rich region.
To better understand genetic associations for NPC within the MHC region of chromosome 6, we conducted an evaluation that pooled two previously conducted NPC case-control studies in Taiwan (N = 591 cases and N = 521 controls). PCR-based genotyping was performed for 12 significant SNPs identified within 6p21 in the Taiwan NPC GWAS and for the HLA-A gene (exons 2 and 3).
After confirming homogeneity between the two studies, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. We found that HLA-A (p-trend = 0.0006) and rs29232 (within the GABBR1 gene; p-trend = 0.005) were independent risk factors for NPC after adjustment for age, gender, study and each other. NPC risk was highest among individuals who were homozygous for the HLA-A*0207 risk allele and carriers of the rs29232 risk allele (A).
Our study suggests that most of the SNPs significantly associated with NPC from GWAS reflect previously identified HLA-A associations. An independent effect of rs29232 (GABBR1), however, remained, suggesting that additional genes within this region might be associated with NPC risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human papillomavirus (HPV) 52 and 58 are oncogenic HPV types prevalent in Asia. Our study aims to explore intratypic variants of HPV 52 and 58 in Taiwan. A total of 11,923 women were enrolled from ...seven townships in 1991–1992. HPV DNA in their cervical cells was detected and typed by EasyChip® HPV blot. Among 424 participants infected with HPV 52 and/or 58, nucleotide variations were determined in cervical cell samples of 406 participants by the polymerase chain reaction sequencing of the long control region, E6 and E7 genes. Nonprototype‐like variants including lineages B and C were detected in 278 (99.3%) of 280 HPV 52 samples. The prototype and prototype‐like group (lineage A) of HPV58 was found in 132 (98.5%) of 134 HPV 58 samples, with sublineage A1, A2 and A3 variant in 14.2, 27.6 and 56.7%, respectively. Among women infected with single HPV 52 type, the C variant (vs. B variant) was associated with an increased prevalence of cytologically diagnosed high‐grade squamous intraepithelial lesion or worse lesions showing an age‐adjusted odds ratio (95% confidence interval, CI) of 5.2 (1.0–27.6) and an increased prevalence of histologically confirmed high‐grade cervical intraepithelial neoplasia or more severe lesions with an age‐adjusted odds ratio (95% CI) of 7.6 (1.3–43.8). It was concluded that frequency distributions of HPV 52 and 58 variants in Taiwan were different from those in European and American populations. The association between C variant of HPV 52 and prevalence of cervical neoplasia needs further validation.
Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to ...identify NPC susceptibles within high-risk NPC families.
We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.
A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.
Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity.
Previously, our laboratory established the role of small, noncoding RNA species
, microRNA (miRNA) including miR-135a in anti-chlamydial immunity in infected hosts. We report here chlamydial ...infection results in decreased miR-135a expression in mouse genital tissue and a fibroblast cell line. Several chemokine and chemokine receptor genes (including CXCL10, CCR5) associated with chlamydial pathogenesis were identified
to contain putative miR-135a binding sequence(s) in the 3' untranslated region. The role of miR-135a in the host immune response was investigated using exogenous miR-135a mimic to restore the immune phenotype associated with decreased miR-135a following
(Cm) infection. We observed miR-135a regulation of Cm-primed bone marrow derived dendritic cells (BMDC)
activation of Cm-immune CD4
T cells for clonal expansion and CCR5 expression. Using a transwell cell migration assay, we explore the role of miR-135a in regulation of genital tract CXCL10 expression and recruitment of CXCR3
CD4
T cells
the CXCL10/CXCR3 axis. Collectively, data reported here support miR-135a affecting multiple cellular processes in response to chlamydial infection.
Nitrosamine consumption and polymorphisms in CYP2E1, the product of which is involved in the activation of nitrosamines into
reactive intermediates, have been shown to be associated with ...nasopharyngeal carcinoma (NPC) risk. Given that reactive intermediates
created during nitrosamine metabolism are capable of DNA damage, we further hypothesized that differences between individuals
in their ability to repair DNA damage might be important in NPC pathogenesis. To evaluate this hypothesis, this study focused
on effects of genetic polymorphisms of DNA repair genes hOGG1 and XRCC1 on the development of NPC. We conducted a case-control study to investigate the genotypes of 334 patients with NPC and 283
healthy community controls matched by sex, age, and residence. The PCR-based RFLP assay was used to identify genetic polymorphisms.
After adjustment for sex, age, and ethnicity, the odds ratio (OR) of developing NPC for hOGG1 codon 326 genotypes of Ser / Cys and Cys / Cys compared with the Ser / Ser genotype was 1.6 (95% CI, 1.0–2.6). For XRCC1 codon 280 genotypes of Arg / His and His / His compared with the Arg / Arg genotype, the OR was 0.64 (95% CI, 0.43–0.96). Among subjects with putative high-risk genotypes for both hOGG1 and XRCC1 , the OR was 3.0 (95% CI, 1.0–8.8). Furthermore, subjects with putative high-risk genotypes for hOGG1 , XRCC1 , and CYP2E1 had an OR of disease of 25 (95% CI, 3.5–177). Polymorphisms of the DNA repair genes hOGG1 (codon 326) and XRCC1 (codon 280) are associated with an altered risk of NPC. Carriers of multiple putative high-risk genotypes have the highest
risk of developing NPC.
A study of nasopharyngeal carcinoma (NPC) families with two or more affected members was conducted in Taiwan (265 families
with 2,444 individuals, 502 affected and 1,942 unaffected) to determine the ...association between NPC and potential etiologic
factors in NPC high-risk families. Similar to results from a previous case-control study in Taiwan, Guangdong salted fish
consumption during childhood, exposure to wood, and betel nut consumption were all associated with elevated NPC risk using
conditional logistic regression, although these associations were not as strong as in the case-control study possibly due
to shared environment among family members. Risk associated with cumulative wood exposure and salted fish consumption before
age 10 was stronger in families with early NPC age-onset odds ratio (OR wood ), 5.10; 95% confidence interval (95% CI), 1.50-17.34; OR fish , 3.94; 95% CI, 1.47-10.55 or three or more affected members (OR wood , 4.41; 95% CI, 1.58-12.30; OR fish , 4.27; 95% CI, 1.10-16.47). In contrast, a tendency for elevated risk was noted for betel nut use in late age-onset families
(OR, 2.44; 95% CI, 1.16-5.13) and the CYP2E1 c2 allele in families with less than three affected members (OR, 2.06; 95% CI, 1.04-3.35). Risk estimates associated with these
exposures were similar when the analyses were restricted to EBV-seropositive subjects. To better adjust for degree of relationship
among family members and residual genetic correlations, we also calculated ORs using a variance components model. The results
from the two methods were similar indicating that the risk estimates from conditional logistic regression were unbiased.
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