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Biomedical subjects

Qingyi Wei

Publications and source records attributed to Qingyi Wei.

At least 73 records · Page 4Linked to original sources
PubMed2005

Radiation response genotype and risk of differentiated thyroid cancer: a case-control analysis.

BACKGROUND: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC. HYPOTHESIS: Germline variants of double-strand break repair genes are markers of DTC risk. OBJECTIVE: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls. STUDY DESIGN: Case-control study. METHODS: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype. RESULTS: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P=.006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9-4.9; P = .078). CONCLUSIONS: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies.

Adolescent↗
PubMed2005

Polymorphisms of vitamin D receptor gene protect against the risk of head and neck cancer.

Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including human squamous cells of the head and neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been described, including a FokI restriction fragment-length polymorphism (RFLP) in exon 2 and an adjacent TaqI RFLP in exon 9. We hypothesized that the VDR FokI and TaqI polymorphisms are associated with the risk of developing squamous cell carcinoma of the head and neck (SCCHN). We conducted a hospital-based, case-control study of 719 SCCHN cases and 821 cancer-free controls (all non-Hispanic Whites) to assess the association between VDR polymorphisms and SCCHN risk. The cases and controls were frequency-matched on age, sex and ethnicity. Polymorphisms at the TaqI and FokI restriction sites were determined from genomic DNA by polymerase chain reaction-RFLP methods. Both homozygous variant genotypes (ff and tt) were associated with a decreased risk of SCCHN [odds ratio (OR)=0.72, 95% confidence interval (CI)=0.53-0.98 and OR=0.64, 95% CI=0.47-0.87, respectively] compared to the common FF and TT genotypes. The VDR variant genotypes were associated with a decreasing risk of SCCHN in a variant allele dose-dependent manner, and the decreasing trend in OR was statistically significant, particularly for the combined genotypes (Ptrend<0.001). These data suggest that the VDR f and t alleles and their genotypes may protect against SCCHN. However, further studies are warranted to confirm these findings.

Adult↗
PubMed2005

Genetic polymorphisms of ataxia telangiectasia mutated and breast cancer risk.

To evaluate the role of genetic polymorphisms of ataxia telangiectasia mutated (ATM) in the etiology of breast cancer, a hospital-based case-control study was conducted in Korea. Nine-hundred ninety-six histologically confirmed incident breast cancer cases and 1,181 cancer-free controls were recruited in Seoul between 1995 and 2003. Genotypes of the ATM polymorphisms-5144A > T, IVS21 + 1049T > C, IVS33 - 55T > C, IVS34 + 60G > A, and 3393T > G were determined by the 5'-nuclease assay. Individual haplotypes were estimated from genotype data by a Bayesian method. Five ATM alleles were found to be in strong linkage disequilibrium (D' > 0.82; P < 0.001). Haplotype frequencies were significantly different between cases and controls (chi2 test, P < 0.001). The ATM IVS21 + 1049 TC or CC, IVS34 + 60 GA or AA, and 3393 TG or GG genotypes were associated with increased breast cancer risk, particularly in premenopausal women [odds ratios (OR), 1.51; 95% confidence interval (CI), 1.11-2.05; OR, 1.42; 95% CI, 1.08-1.88; and OR, 1.37; 95% CI, 1.04-1.80, respectively]. Compared with diploid of TCCAG:TCCAG, the most common haplotype, the ATTGT:ATTGT was associated with decreased risk of breast cancer with borderline significance (OR, 0.77; 95% CI, 0.58-1.04) and TCCAG:ATCGT and ATTGT:ACCAG were associated with increased breast cancer risk (OR, 2.30; 95% CI, 1.18-4.48 and OR, 2.43; 95% CI, 1.1.07-5.52, respectively) after adjusting for age, education, age at first full-term pregnancy, parity, family history of breast cancer, alcohol consumption, and smoking. As the number of ATTGT haplotype decreased, the risk of breast cancer increased (P for trend < 0.01). Our results thus suggest that genetic polymorphisms of ATM play an important role in the development of breast cancer in Korean women.

Ataxia Telangiectasia Mutated Proteins↗
PubMed2005

Polymorphisms of methionine synthase and methionine synthase reductase and risk of squamous cell carcinoma of the head and neck: a case-control analysis.

Although tobacco and alcohol use are the major risk factors, folate deficiency has been implicated in the risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that polymorphisms of methionine synthase (MTR) and methionine synthase reductase (MTRR) in the folate metabolic pathway are associated with SCCHN risk. In a hospital-based case-control study of 721 SCCHN cases and 1,234 controls of non-Hispanic Whites, frequency matched by age, sex, and smoking status, we genotyped the MTR A2756G and MTRR G66A polymorphisms. We found that the MTR variant AG and AG/GG genotypes were associated with a significantly increased SCCHN risk [adjusted odd ratio (OR), 1.31; 95% confidence interval (95% CI), 1.07-1.60 for AG and OR, 1.28; 95% CI, 1.05-1.56 for AG/GG] compared with the AA genotype. In contrast, the MTRR variant AA genotype was associated with a significantly decreased SCCHN risk (OR, 0.68; 95% CI, 0.52-0.90) compared with the 66GG genotype. When the two polymorphisms were evaluated together by the number of risk alleles, the SCCHN risk was significantly increased in a dose-dependent manner (P(trend) = 0.002). The risk of SCCHN was 1.47 (95% CI, 1.08-1.99) for one risk allele, 1.67 (95% CI, 1.23-2.27) for two risk alleles, and 1.74 (95% CI, 1.18-2.54) for three or four risk alleles compared with the wild-type (0 risk allele) genotype. In conclusion, our data provide evidence that support the association between the MTR A2756G and MTRR G66A polymorphisms and SCCHN risk and that these two polymorphisms may have a joint effect on risk of SCCHN.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2005

XRCC1 polymorphisms and cancer risk: a meta-analysis of 38 case-control studies.

Several potential functional polymorphisms (Arg194Trp, Arg280His, Arg399Gln) in the DNA base excision repair gene X-ray repair cross-complementing group 1 (XRCC1) have been implicated in cancer risk. Our meta-analysis on total of 11,957 cancer cases and 14,174 control subjects from 38 published case-control studies showed that the odds ratio (OR) for the variant genotypes (Trp/Trp + Arg/Trp) of the Arg194Trp polymorphism, compared with the wild-type homozygote (Arg/Arg), was 0.89 [95% confidence interval (95% CI), 0.81-0.98] for all tumor types without between-study heterogeneity. Similarly, the overall risk for the combined variant genotypes (His/His + Arg/His) of the Arg280His, compared with the wild homozygote (Arg/Arg), was 1.19 (95% CI, 1.00-1.42). However, there was no main effect in either recessive or dominant modeling for the Arg399Gln, and the variant Gln/Gln homozygote was not associated with overall cancer risk (OR, 1.01; 95% CI, 0.90-1.14). The analyses suggest that XRCC1 Arg194Trp, Arg280His polymorphisms may be biomarkers of cancer susceptibility and a single larger study with thousands of subjects and tissue-specific biochemical and biological characterization is warranted to further evaluate potential gene-to-gene and gene-to-environment interactions on XRCC1 polymorphisms and cancer risk.

Case-Control Studies↗
PubMed2005

Sex differences in risk of lung cancer associated with methylene-tetrahydrofolate reductase polymorphisms.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer. The MTHFR gene has three nonsynonymous single nucleotide polymorphisms (i.e., C677T, A1298C, and G1793A) that have a minor allele frequency of >5%. We investigated the associations between the frequencies of MTHFR variant genotypes and risk of lung cancer in a hospital-based case-control study of 1,051 lung cancer patients and 1,141 cancer-free controls in a non-Hispanic White population. We found that compared with the MTHFR 1298AA genotype, the 1298CC genotype was associated with a significantly increased risk of lung cancer in women [(odds ratio (OR), 2.09; 95% confidence interval (95% CI), 1.32-3.29)] but not in men (OR, 0.95; 95% CI, 0.62-1.45). The MTHFR 677TT genotype was associated with a significantly decreased risk of lung cancer in women (OR, 0.60; 95% CI, 0.40-0.92) but not in men. No association was found between the MTHFR G1793A polymorphism and risk of lung cancer. Further analysis suggested evidence of gene-dietary interactions between the MTHFR C677T polymorphism and dietary intake of vitamin B6, vitamin B12, and methionine in women and evidence of gene-environment interactions between the MTHFR C677T and A1298C polymorphisms and tobacco smoking in men. In conclusion, the polymorphisms of MTHFR may contribute to the risk of lung cancer in non-Hispanic Whites and modify the risk associated with the dietary and environmental exposure in a sex-specific manner.

Aged↗
PubMed2005

Expression of nucleotide excision repair proteins in lymphocytes as a marker of susceptibility to squamous cell carcinomas of the head and neck.

The transcript levels of nucleotide excision repair (NER) genes were shown to be associated with risk of squamous cell carcinomas of the head and neck (SCCHN). However, this association may be biased, because the transcript level does not necessarily reflect the level of protein expression. To address this issue, we did a pilot study to test the hypothesis that the expression of six core NER proteins is associated with risk of SCCHN. We obtained cultured lymphocytes from 57 patients with newly diagnosed SCCHN patients and 63 cancer-free controls. We transfected some of the lymphocytes with both damaged and undamaged plasmid DNA and quantified NER protein levels in these lymphocytes using a reverse-phase protein microarray. The relative NER protein levels in the 63 controls were highly correlated with each other (P<0.001 for all). Compared with the controls, the cases had lower expression levels for all the NER proteins, particularly XPC and XPF, which were reduced by about 25% (P<0.01). When we used the median expression levels of the NER proteins in the controls as cutoff values, we found that a significantly increased risk of SCCHN was associated with low expression of XPA [odds ratio (OR), 2.99; 95% confidence interval (CI), 1.22-7.47], XPC (OR, 2.46; 95% CI, 1.04-5.87), XPD (OR, 3.02; 95% CI, 1.18-7.76), and XPF (OR, 5.29; 95% CI, 2.01-13.9), but not ERCC1 and XPG, after adjustment for age, sex, ethnicity, smoking, alcohol use, and sample storage time. In a multivariate logistic regression model that included all covariates and NER proteins, however, only low expression of XPF remained a significant risk factor for SCCHN (OR, 11.5; 95% CI, 2.32-56.6). These results suggest that XPF may be a crucial rate-limiting factor in DNA repair and that the reverse-protein microarray assay may be a useful tool for measuring protein markers of susceptibility to cancer.

Biomarkers, Tumor↗
PubMed2005

Association of hsp70-2 and hsp-hom gene polymorphisms with risk of acute high-altitude illness in a Chinese population.

High-altitude illness (HAI) is a potentially fatal condition involving genetic and environmental components. Accumulated experimental evidence suggests that heat shock proteins (Hsps), especially HSP70, can protect cells and organs against different types of damage. We investigated whether genetic variation in constitutive and inducible hsp70 genes could be associated with risk of HAI. The association between polymorphisms of the HSP70 family genes and risk of HAI was determined in 56 patients with HAI and in 100 matched controls by genotyping for the polymorphisms +190 G/C, +1267 A/G, 2437 G/C in the hsp70-1, hsp70-2, and hsp70-hom genes by using polymerase chain reaction-restriction fragment length polymorphism. The data showed that there was no statistically significant difference in the genotype and allele distributions of hsp70-1, in hsp70-2 allele and hsp70-2 A/A and A/B genotypes, and in allele distribution of hsp70-hom among patients with HAI and controls (chi2 test, P > 0.05). However, there was a significantly higher frequency of hsp70-2 B/B and hsp70-hom A/A and B/B genotypes and a significantly lower frequency of the hsp70-hom A/B genotype in the HAI patients compared with the controls (P < 0.05 for all). The risk associated with the hsp70-2 B/B and hsp70-hom A/A, A/B, and B/B genotypes were 4.017 (95% CI = 1.496-10.781; P = 0.004), 2.434 (95% CI = 1.184-5.003; P = 0.012), 0.299 (95% CI = 0.148-0.602, P = 0.001), and 5.880 (95% CI =1.145-30.196, P = 0.026), respectively. Our results suggest that individuals with hsp70-2 B/B and hsp70-hom A/B and B/B genotypes may be more susceptible to HAI, whereas those with hsp70-hom A/B genotype may be tolerant to HAI. Further studies in individuals of different age and sex are warranted to elucidate the underlying mechanisms of this association and the possible functions of different genotypes of hsp70-2 and hsp70-hom under hypoxic stress.

Adult↗
PubMed2005

Plasma antibodies to heat shock protein 60 and heat shock protein 70 are associated with increased risk of electrocardiograph abnormalities in automobile workers exposed to noise.

In the living and working environment, stressful factors, such as noise, can cause health problems including cardiovascular diseases and noise-induced hearing loss. Some heat shock proteins (Hsps) play an important role in protecting cardiac cells against ischemic injury, and antibodies against these Hsps are associated with the development and prognosis of atherogenesis, coronary heart disease, and hypertension. Whether the presence of such antibodies is associated with abnormal electrocardiography (ECG) in stressed autoworkers exposed to chronic noise is presently unknown. Therefore, we investigated the association between the levels of plasma anti-Hsp60 and anti-Hsp70 with electrocardiograph abnormality in 396 autoworkers exposed to different noise levels by using Western blot, ECG, and multivariate logistic regression analysis. The results showed that the increase in levels of anti-Hsp70 was associated with a higher risk of ECG abnormalities characteristic of chronic myocardial ischemia (P < 0.05), conductive abnormality (P < 0.01), or heart displacement (P < 0.05); in contrast, elevated anti-Hsp60 was related to ECG abnormalities characteristic of sinus arrhythmia, chronic myocardial ischemia, and ectopic rhythm (P < 0.01 for all). Overall, high levels of both anti-Hsp70 and anti-Hsp60 were associated with significantly increased risk of ECG abnormalities (odds ratio [OR] = 1.73 and 95% confidence interval [Cl] = 1.04-2.86 for anti-Hsp70 and OR = 1.36 and 95% Cl = 1.07-1.72 for anti-Hsp60) with and without adjustment for cumulative noise exposure (OR = 1.96 and 95% Cl = 1.20-3.21 for anti-Hsp70 and OR = 3.93 and 95% Cl = 1.72-8.92 for anti-Hsp60). These findings suggest that the production of both anti-Hsp70 and anti-Hsp60 may be independent risk factors for the development and progression of abnormal ECG and therefore possibly cardiovascular diseases in autoworkers exposed to occupational noise.

Adult↗
PubMed2005

Methylenetetrahydrofolate reductase polymorphisms/haplotypes and risk of gastric cancer: a case-control analysis in China.

Studies have suggested that low dietary folate intake is associated with an increased risk of gastric cancer. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and influences DNA methylation and nucleotide synthesis. MTHFR is highly polymorphic and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. We hypothesized that three MTHFR common variants (i.e. C677T, A1298C and G1793A) and their haplotypes are associated with the risk of gastric cancer. To test this hypothesis, we genotyped these polymorphisms in a population-based case-control study of 320 incident gastric adenocarcinoma cases and 313 cancer-free controls in a Chinese population. Consistent with our previous observations, the 677TT genotype was associated with a significantly increased risk for gastric cancer (adjusted OR =1.79, 95% CI =1.02-3.15) compared with the 677CC genotype; the association was more evident for gastric cardia adenocarcinoma (adjusted OR =2.60, 95% CI =1.30-5.21). When we used the haplotype analyses and assumed MTHFR 677T, 1298C and 1793A as risk alleles, individuals with 6 variant alleles had a significantly (4.64-fold) increased risk for gastric cardia adenocarcinoma (OR =4.64, 95% CI =1.34-16.01) compared with those having 0-2 variants. These findings suggest that the MTHFR common variants and their haplotypes may play a role in the etiology of gastric cancer, particularly gastric cardia adenocarcinoma. Future studies using large sample sizes and incorporating detailed data on dietary folate intake and related serological measurements are warranted to confirm our findings.

Adenocarcinoma↗
PubMed2004

Case-control analysis of thymidylate synthase polymorphisms and risk of lung cancer.

Although tobacco smoking is the primary risk factor for lung cancer, low dietary folate intake and suboptimal DNA repair capacity also contribute to lung cancer risk. Thymidylate synthase (TYMS) is involved in the metabolism of folate and the provision of nucleotides needed for DNA synthesis and repair. Thus, a variation in TYMS functions likely plays a role in the etiology of lung cancer. The TYMS gene has a tandem repeat polymorphism (two or three 28 bp) in the TYMS enhancer region (TSER) and a 6 bp deletion/insertion polymorphism in the TS 3'-untranslated region (TS3'UTR or 1494del6). We investigated the frequencies of these two polymorphisms in a hospital-based case-control study of 1055 lung cancer patients and 1140 cancer-free controls in a non-Hispanic white population and genotyped for these two polymorphisms. We found that the TS3'UTR, but not the TSER, variant was associated with the risk of lung cancer. Compared with homozygotes for the TS3'UTR 6 bp deletion (0bp/0bp), the 6bp/0bp+6bp/6bp genotypes were associated with a significantly increased risk of lung cancer [odds ratio (OR) = 1.52, 95% confidence interval (CI) = 1.12-2.06]. In stratification analysis the risk associated with the 0bp/6bp+6bp/6bp genotype was more pronounced in subjects who were >55 years old (OR = 1.57, 95% CI = 1.10-2.23), males (OR = 1.88, 95% CI = 1.22-2.89), current (OR = 2.04, 95% CI = 1.26-3.29) and heavy smokers (OR = 1.73, 95% CI = 1.10-2.70) and current drinkers (OR = 3.17, 95% CI = 1.78-5.64).Furthermore, significant gene-dietary interactions were found between TS3'UTR and alcohol consumption and between TSER and vitamin B(12) intake. In conclusion, the polymorphisms of TYMS are likely to contribute to the risk of lung cancer in non-Hispanic whites and interact with dietary factors in lung cancer development.

3' Untranslated Regions↗
PubMed2004

Thymidylate synthase 5'- and 3'-untranslated region polymorphisms associated with risk and progression of squamous cell carcinoma of the head and neck.

PURPOSE: Folate deficiency and reduced DNA repair capacity are established risk factors for squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that polymorphisms of the thymidylate synthase (TYMS) gene, which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk. EXPERIMENTAL DESIGN: In a hospital-based case-control study of 704 SCCHN cases and 1,085 controls, frequency matched by age, sex, and ethnicity, we genotyped the TSER (thymidylate synthase in the 5'-untranslated enhanced region) and TS3'UTR (thymidylate synthase in the 3'-untranslated region) polymorphisms. RESULTS: The TS3'UTR 0bp/0bp genotype was associated with a significantly decreased risk of SCCHN [adjusted odd ratio (OR) = 0.67, 95% confidence interval (CI) = 0.47-0.94] compared with the 6bp/6bp genotype, but the TSER polymorphism had no main effect on risk of SCCHN. When we evaluated the two polymorphisms together by the number of protective alleles (the TSER 3R and TS3'UTR 0bp alleles), we found that the combined genotypes with four protective alleles (the TSER 3R3R and TS3'UTR 0bp/0bp) was associated with significantly decreased SCCHN risk (OR = 0.60, 95% CI = 0.37-0.98). In addition, the TS3'UTR 0bp genotypes were associated in an allele dose-dependent manner with a decreased risk of overall stage IV oral cancer (OR = 0.84, 95% CI = 0.52-1.34 for the 6bp/0bp genotype and OR = 0.26, 95% CI = 0.08-0.87 for the 0bp/0bp genotype; P(trend) = 0.035). CONCLUSION: The TSER and TS3'UTR polymorphisms are associated with SCCHN risk. The TSER 3R and TS3'UTR 0bp alleles seemed to jointly protect against SCCHN. In particular, the 0bp allele seemed to protect against oral cancer progression.

3' Untranslated Regions↗
PubMed2004

Interleukin-1B gene promoter variants are associated with an increased risk of gastric cancer in a Chinese population.

Studies suggest that IL-1beta (encoded by IL-1B gene) is a pro-inflammatory cytokine and potent inhibitor of gastric acid secretion, which is proposed as a key determinant in gastric carcinogenesis. Two potentially functional polymorphisms (C-31T and T-511C) in the IL-1B promoter were suggested to be correlated with alteration of Helicobacter pylori infection and IL-1beta expression and therefore may be associated with risk of gastric cancer. To test the hypothesis that these two polymorphisms are associated with gastric cancer risk, we performed a case-control study of 280 histologically confirmed gastric cancer patients and 258 age, sex frequency-matched cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks (adjusted odds ratio [OR] and 95% confidence interval [CI]) associated with the IL-1B variant genotypes were 1.64 (95% CI, 1.01-2.66) for -31TT and 1.52 (95% CI, 0.91-2.54) for -511CC, respectively, compared with their wild-type homozygotes. The risks were significantly more evident in individuals with H. pylori infection (adjusted OR, 2.14; 95% CI, 1.13-4.06 for -31TT; adjusted OR, 2.00; 95% CI, 1.02-3.89 for -511CC), which was consistent with the biological effects of IL-1beta. When we used the haplotype analyses and assumed the IL-1B -31T and -511C as risk alleles, no synergistic effect was found between these two loci. These findings indicate that these two IL-1B promoter variants may contribute to the risk of developing gastric cancer in the Chinese population, especially in individuals with H. pylori infection.

Asian People↗
PubMed2004

Repair of mitomycin C cross-linked DNA in mammalian cells measured by a host cell reactivation assay.

DNA repair capacity in a cell could be detected by a host-cell reactivation assay (HCR). Since relation between DNA repair and genetic susceptibility to cancer remains unclear, it is necessary to identify DNA repair defects in human cancer cells. To assess DNA repair for breast cancer susceptibility, we developed a modified HCR assay using a plasmid containing a firefly luciferase gene damaged by mitomycin C (MMC), which forms interstrand cross-link (ICL) adducts. In particular, interstrand cross-link is thought to induce strand breaks being repaired by homologous recombination. The MMC-ICLs were verified by electrophoresis. Damaged plasmids were transfected into apparently normal human lymphocytes and NER-deficient XP cell lines and the DNA repair capacity of the cells were measured by quantifying the activity of the firefly luciferase. MMC lesion was repaired as much as UV adducts in normal lymphocytes and the XPC cells. However, the XPA cells have a lower repair capacity for MMC lesion than the XPC cell, indicating that the XPA protein may be involved in initial damage recognition of MMC-ICL adducts. Since several repair pathways including NER and recombination participate in MMC-ICL removal, this host cell reactivation assay using MMC-ICLs can be used in exploring DNA repair defects in human cancer cells.

Animals↗
PubMed2004

p73 G4C14-to-A4T14 polymorphism and risk of lung cancer.

Genetic variants in genes controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate lung cancer risk. p73 has some p53-like activity and plays an important role in modulating these processes. The noncoding region of exon 2 of the p73 gene has two polymorphisms that are in complete linkage disequilibrium with one another, which may alter translation efficiency of the p73 protein. To test the hypothesis that this p73 polymorphism plays a role in the etiology of lung cancer, we conducted a hospital-based case-control study of 1054 patients newly diagnosed with lung cancer and 1139 cancer-free controls and evaluated the association between the p73 variant AT allele and risk of lung cancer. Cancer-free controls were frequency matched to the cases by age (+/-5 years), sex, and smoking status, and all subjects were non-Hispanic whites. The variant AT allele and genotypes were more common among the cases than among the controls (P = 0.0007 and P < 0.001, respectively). Compared with the GC/GC genotype, the variant GC/AT and AT/AT genotypes were associated with a statistically significantly increased risk for lung cancer [adjusted odds ratio (OR) = 1.32, 95% confidence interval (CI), 1.10-1.59 and OR = 1.54, 95% CI, 1.05-2.26, respectively] in an allele dose-effect relationship (trend test: P < 0.001). The risk associated with the AT allele (GC/AT+AT/AT) was more pronounced in younger (</=50 years) individuals (OR = 1.53, 95% CI, 1.00-2.37), men (OR = 1.61, 95% CI, 1.26-2.06), light smokers (OR = 1.58, 95% CI, 1.17-2.14), and squamous cell lung carcinoma (OR = 1.79, 95% CI, 1.32-2.42). These results suggest that this p73 polymorphism may be a marker for susceptibility to lung cancer.

Adult↗
PubMed2004

Matched-pair analysis of survival of never smokers and ever smokers with squamous cell carcinoma of the head and neck.

PURPOSE: To compare survival rates between patients with squamous cell carcinoma of the head and neck (SCCHN) without a history of smoking (never smokers) and those with a current or previous history of smoking (ever smokers). PATIENTS AND METHODS: Fifty never smokers with newly diagnosed SCCHN were matched to 50 ever smokers according to sex, age, tumor site, overall stage, nodal stage, and treatment. Survival analysis was performed using Kaplan-Meier estimates. Matched-pair survival was compared using the Cox proportional hazards model. RESULTS: The never smokers had a greater overall survival (P =.020), disease-specific survival (P =.022), and recurrence-free survival (P =.016). Furthermore, matched-pair analysis demonstrated smoking was associated with a significant increase in risk of overall death (relative risk [RR] = 3.50; 95% CI, 1.14 to 10.77; P =.029), risk of death owing to disease (RR = 3.98; 95% CI, 1.11 to 14.33; P =.034), and risk of disease recurrence (RR = 3.29; 95% CI, 1.18 to 9.14; P =.023). Smoking was associated with three-fold increases in risk for overall death, death owing to disease, and recurrence after adjustment for cancer-associated symptom severity and alcohol use, but the 95% CI for these adjusted risk estimates each included the null. CONCLUSION: Survival differed significantly between never smokers and ever smokers with SCCHN. These results are not substantively explained by differences in cancer-associated symptoms or alcohol use, but the CIs are wide and some imprecision remains. Regardless, possible fundamental differences in SCCHN between ever smokers and never smokers may exist, and further molecular characterization of these tumors is needed to determine whether biologic differences needing targeted therapies exist.

Adult↗
PubMed2004

Correlation of lymphocyte heat shock protein 70 levels with neurologic deficits in elderly patients with cerebral infarction.

PURPOSE: To assess the association between heat shock protein 70 (HSP70) levels and the severity of ischemic stroke in elderly patients. METHODS: We conducted a case-control study to investigate the changes in lymphocyte HSP70 levels by immunoblot in 65 elderly patients with mild (n = 22), intermediate (n = 21), or severe (n = 22) stroke, and in 34 healthy controls. We analyzed correlations between HSP70 levels and neurologic deficit scores on days 1, 15, and 30 after the onset of stroke. RESULTS: Mean (+/- SD) HSP70 levels were higher in all stroke patients compared with controls (mild stroke: 709 +/- 194 units; intermediate: 585 +/- 165 units; severe: 421 +/- 124 units; controls: 86 +/- 34 units on day 1). Patients with mild stroke had higher levels at day 1 and 15 than did patients with severe stroke. HSP70 levels decreased rapidly from days 1 to 30 in all patients, except in patients with severe stroke, in whom levels decreased slowly between days 15 and 30. There were significant negative correlations between HSP70 levels and neurologic deficit scores in patients on days 1 (r = -0.53, P < 0.001) and 15 (r = -0.54, P < 0.001), but a positive correlation on day 30 (r = 0.49, P < 0.001). CONCLUSION: These data suggest that HSP70 may be a marker for neuroprotection in the early stage of ischemic stroke and a marker for a crisis in the later stages of severe cerebral infarction. Further studies on the use of lymphocyte HSP70 levels in predicting clinical outcomes and underlying mechanisms in cerebral infarction are warranted.

Aged↗