Biomedical subjects

Qingyi Wei

Publications and source records attributed to Qingyi Wei.

At least 55 records · Page 3Linked to original sources

PubMed2005

Functional polymorphisms of matrix metalloproteinase-9 are associated with risk of occurrence and metastasis of lung cancer.

PURPOSE: Matrix metalloproteinase 9 (MMP-9) plays critical roles in cancer development and aggression. Nonsynonymous single-nucleotide polymorphisms (SNP) in the functional domain of the MMP-9 gene may influence substrate and inhibitor binding and contribute to cancer predisposition and aggression. PATIENTS AND METHODS: To test our hypothesis that common nonsynonymous SNPs, R279Q, P574R, and R668Q, in MMP-9 are associated with lung cancer development and metastasis, we conducted a case-control study of 744 patients with incident lung cancer and 747 cancer-free controls in Southeast China. Multivariate logistic regression analysis was used to calculate adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: We found that compared with the 279QQ genotype, the 279RR genotype was associated with significant elevated risk of lung cancer with metastasis (adjusted OR, 1.79; 95% CI, 1.03-3.08), whereas the 574PR heterozygote and 574PP homozygote had 1.46-fold (95% CI, 0.94-2.26) and 1.69-fold elevated risk (95% CI, 1.10-2.60), respectively, compared with the 574RR genotype. When we examined the combined effect of R279Q and P574R and used the 279R and 574P as the risk alleles, a significantly increased risk of lung cancer was associated with both the genotypes containing "1 to 2 risk alleles" (adjusted OR, 2.16; 95% CI, 1.30-3.59) and containing ">2 risk alleles" (adjusted OR, 2.44; 95% CI, 1.48-4.03), and it was more pronounced in 290 lung cancer cases with metastasis [adjusted OR, 2.30 (95% CI, 1.09-4.85) for the 1 to 2 risk alleles subgroup and adjusted OR, 2.82 (95% CI, 1.35-5.88) for the >2 risk alleles subgroup], compared with those without any risk alleles. However, no overall significant associations were observed between R668Q and lung cancer risk in this study population. CONCLUSION: These findings indicate that the potentially functional polymorphisms, MMP-9 P574R and R279Q, may confer the biomarker in the occurrence and metastasis of primary lung cancer. Further functional studies including these two genetic variants are warranted to confirm our findings.

Adult↗

PubMed2005

Gastrostomy in oropharyngeal cancer patients with ERCC4 (XPF) germline variants.

PURPOSE: ERCC4 (XPF) plays a role in both recombinant DNA repair and nucleotide excision repair, which involve repairing radiation-induced genetic damage. We hypothesized that two ERCC4 single-nucleotide polymorphisms are associated with normal-tissue toxicity in patients treated with radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). METHODS AND MATERIALS: A retrospective review of the medical records of 130 patients with OPSCC who were prospectively recruited into a molecular epidemiologic study was performed to determine whether a long-term percutaneous feeding gastrostomy (LPFG) tube (a tube required for more than 180 days) had been used during and after definitive radiotherapy. We determined the genotype of the ERCC4 G1244A and T2505C polymorphisms using standard polymerase chain reaction-restriction fragment-length polymorphism techniques on DNA extracted from peripheral blood lymphocytes. RESULTS: Of 130 patients, 100 (77%) were evaluable for the ERCC4 G1244A polymorphism in exon 8, and 122 (94%) were evaluable for the ERCC4 T2505C polymorphism in exon 11. The ERCC4 G1244A polymorphism was associated with a decreased need for LPFG, but this was not statistically significant (adjusted odds ratio = 0.53; 95% confidence interval, 0.10-2.78). Sixteen (32%), 9 (14%), and 1 (10%) of patients with the wild-type homozygous TT genotype of ERCC4 T2505C, the heterozygous TC genotype, and the homozygous CC polymorphic genotype, respectively, required LPFG. These results suggest that the ERCC4 2505C allele was associated with a reduced need for LPFG (adjusted odds ratio = 0.20; 95% confidence interval, 0.06-0.67). Furthermore, the need for LPFG was reduced by having more than 1 ERCC4 2505C allele and further for having both the ERCC4 1244A and 2505C polymorphic alleles, but this was not statistically significant. In addition, the actual time of gastrostomy dependence was associated with the T2505C polymorphism based on the Kaplan-Meier method (p = 0.03). CONCLUSIONS: Our findings suggest that the ERCC4 T2505C polymorphism may be associated with improved recovery from radiation treatment toxicity in patients with OPSCC. Further study with larger sample sizes and prospective measure of radiotherapy-induced toxicity is warranted.

Adult↗

PubMed2005

Methylation and messenger RNA expression of p15INK4b but not p16INK4a are independent risk factors for ovarian cancer.

PURPOSE: The purpose of this research was to compare methylation status and mRNA expression of p15INK4b and p16INK4a in serous epithelial ovarian cancer tissues and normal ovarian tissues. EXPERIMENTAL DESIGN: We analyzed the DNA methylation status and mRNA expression of p15INK4b and p16INK4a in 52 ovarian cancer specimens and 40 normal ovarian specimens by using methylation-specific PCR and real-time reverse transcription-PCR, respectively. RESULTS: Although the p15INK4b and p16INK4a mRNA expression levels were highly correlated with each other (P < 0.001), the methylation status did not seem to be linked with levels of mRNA expression, as no association between the two events was found for either gene. Promoter hypermethylation of p15(INK4b) was more common in ovarian cancer (30.8% for the 52 cases) than in normal ovaries (5% for the 40 controls without ovarian cancer; P = 0.005) but not methylation of p16INK4a (25% for cancer versus 37.5% for normal; P = 0.288). The relative mRNA expression levels of p15INK4b were significantly lower in ovarian cancer (12.9%) than in normal ovaries (41.7%; P = 0.008) but not those of p16INK4a (27% for cases versus 32.8% for controls; P = 0.754). Only high methylation rate and low mRNA expression of p15INK4b were independent risk factors for ovarian cancer (adjusted odds ratio, 5.67; 95% confidence interval, 0.85-37.9 for high methylation rate and odds ratio, 8.98; 95% confidence interval, 1.58-50.9 for low mRNA expression, respectively). CONCLUSIONS: Our results suggest that epigenetic alterations in p15INK4b but not p16INK4a have an important role in ovarian carcinogenesis and that mechanisms other than methylation may exist to reduce gene expression of p15INK4b in ovarian cancer.

Aged↗

PubMed2005

DNA repair gene XPC genotypes/haplotypes and risk of lung cancer in a Chinese population.

DNA repair is central to normal cellular functions, and polymorphisms of DNA repair genes may cause variation in DNA repair capacity in the general population. Newly identified polymorphisms of xeroderma pigmentosum group C (XPC), one of the nucleotide excision repair genes, were shown to contribute to genetic susceptibility to cancer. In this study, we hypothesized that 2 exonic variants C499T and A939C and their haplotypes in XPC are associated with lung cancer risk. To test this hypothesis, we performed a case-control study of 320 histologically confirmed lung cancer patients and 322 age and sex frequency-matched cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that the risks [adjusted odds ratios (ORs) and 95% confidence intervals (CIs)] associated with the XPC variant genotypes were 1.57 (95% CI = 1.13-2.19) for 499CT/TT and 1.21 (95% CI = 0.87-1.69) for 939AC/CC compared with the 499CC and 939AA wild-type homozygotes, respectively. Individuals with both putative risk genotypes (499CT/TT and 939AC/CC) had a greater risk of lung cancer (adjusted OR = 2.37; 95% CI = 1.33-4.21) compared with individuals with both wild-type genotypes (499CC and 939AA). When we performed the haplotype analysis and assumed the XPC 499T and 939C as risk alleles, the adjusted ORs increased as the number of variants in the haplotype genotypes increased (p(trend) < 0.001). In the stratified analysis, the greatest risk was found in smokers having the combined variant genotypes (adjusted OR = 7.36; 95% CI = 3.19-17.00) compared with nonsmokers having both wild-type genotypes and in smokers with 2 or 3 haplotype variants (adjusted OR = 7.27; 95% CI = 3.37-15.68) compared with nonsmokers having 0 haplotype variant. These findings indicate that XPC exonic variants may contribute to the risk of lung cancer in the Chinese population, and these variant genotypes may modulate the risk of lung cancer associated with smoking.

Alleles↗

PubMed2005

Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone receptor status, and breast cancer risk.

PURPOSE: Genetic polymorphisms of DNA repair genes seem to determine the DNA repair capacity, which in turn may affect the risk of breast cancer. To evaluate the role of genetic polymorphisms of DNA repair genes in breast cancer, we conducted a hospital-based case-control study of Korean women. EXPERIMENTAL DESIGN: We included 872 incident breast cancer cases and 671 controls recruited from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of selected DNA repair genes were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4 921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C > T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 -93G > A, and Ile219Val). RESULTS: We found that the RAD52 2259 CT or TT, hMLH1 -93 GG, and ERCC1 8092 AA genotypes were associated with breast cancer risk after adjustment for known risk factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR, 1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When Bonferroni's method was used to correct for multiple comparisons for nine polymorphisms with P = 0.005, all of these associations were not significant. However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were more evident for the estrogen/progesterone receptor-negative cases (OR, 2.03; 95% CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). CONCLUSION: Our findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be associated with breast cancer risk in Korean women.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Polymorphisms of thymidylate synthase in the 5'- and 3'-untranslated regions associated with risk of gastric cancer in South China: a case-control analysis.

Fruits and certain vegetables have a protective effect on gastric cancer (GC) and folate is one of the nutrients in fruits and vegetables. We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. In a population-based case-control study of 337 GC cases and 326 controls, frequency-matched by age, sex and residential areas in a southern Chinese population, we genotyped the 28 bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and the 6 bp deletion/insertion at bp 1494 in the TYMS 3'-untranslated region (TS3'UTR). We found that although the TSER polymorphism had no main effect on GC risk, the TS3'UTR 6 bp/6 bp genotype was associated with a significantly increased risk of GC [adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.18-3.25], especially the non-cardiac gastric cancer (2.16, 1.22-3.82), compared with the 0 bp/0 bp genotype. However, when we evaluated these two polymorphisms together and used the combined genotype with zero variant allele (TSER 2R and TS3'UTR 6 bp variant alleles) as the reference, we found that the combined genotype with three or four variant alleles was associated with a significantly increased risk of GC (2.06, 1.12-3.79), especially the non-cardiac gastric cancer (2.33, 1.19-4.59), and this significant association was more pronounced among older women (>60 years old), non-smokers, and never tea drinkers. In conclusion, the TYMS polymorphisms, especially the TS3'UTR polymorphism, are associated with GC risk, especially the non-cardiac gastric cancer, and the TSER 2R and TS3'UTR 6 bp alleles may jointly play a role in the etiology of GC in the southern Chinese population. Larger studies are warranted to verify these findings.

3' Untranslated Regions↗

PubMed2005

Methylenetetrahydrofolate reductase polymorphisms and risk of squamous cell carcinoma of the head and neck: a case-control analysis.

Folate deficiency is implicated in cancer risk that may be modulated by a genetic variation in the methylenetetrahydrofolate reductase (MTHFR) gene in folate metabolism. We hypothesized that genetic variants in MTHFR are associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We genotyped 3 MTHFR polymorphisms (C677T, A1298C and G1793A) and estimated their haplotypes in a hospital-based case-control study of 537 SCCHN cases and 545 cancer-free controls. The controls were frequency-matched to the cases by age (+/- 5 years), sex, ethnicity and smoking status. We found that the MTHFR 1298AC/CC genotypes were associated with an approximately 35% reduction in risk of SCCHN (adjusted odds ratio = 0.65; 95% CI = 0.51-0.82) compared to the AA genotype. The MTHFR 677CT and 1793GA/AA genotypes were associated with nonsignificant increased risk of SCCHN compared to the 677CC and 1793GG genotypes, respectively. We estimated that there were 8 haplotypes and 16 haplotype genotypes based on these 3 variants. When we used the haplotypes and assumed that the 677T, 1298A and 1793A alleles were risk alleles, the adjusted odds ratios increased as the number of risk alleles increased: 1.00 for 0-1 variant, 1.85 (1.3-2.5) for any 2 risk alleles and 1.93 (1.4-2.7) for any 3 risk alleles. These results suggest that all 3 MTHFR polymorphisms may play a role in the susceptibility to SCCHN among non-Hispanic whites. Future studies should incorporate detailed data on alcohol consumption, dietary folate intake and related serologic measurements.

Adult↗

PubMed2005

Genetic polymorphisms of p21 are associated with risk of squamous cell carcinoma of the head and neck.

The p21 (Waf1/Cip1/CDKN1A) protein regulates the transition from the G1 to the S phase and has an important role in modulating cell-cycle control, apoptosis and cell growth. Two polymorphisms of the p21 gene at codon 31 (p21 C98A, dbSNP rs1801270) and at the 3' untranslated region (p21 T70C, dbSNP rs1059234) may have an effect on the protein function and may thus play a role in the development of cancer. We hypothesized that these two p21 polymorphisms are associated with the risk of squamous cell carcinoma of the head and neck (SCCHN). We tested this hypothesis in a hospital-based case-control study of 712 patients newly diagnosed with SCCHN and 1222 cancer-free controls who were frequency-matched by age, sex and ethnicity. All subjects were non-Hispanic whites. Our results showed that the variant alleles and genotypes were more common among cases than among controls (P < 0.001 and P = 0.013 for p21C70T, and P < 0.001 and P = 0.035 for p21C98A, respectively). Compared with the p21 70CC genotype, there was a significantly greater risk of SCCHN associated with the variant p21 70TC [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.12-1.93] and combined p21 70TC/TT (OR = 1.49, 95% CI = 1.14-1.95) genotypes. Similarly, compared with the p21 98CC genotype, there was also a significantly greater SCCHN risk associated with the variant p21 98AC (OR = 1.32, 95% CI = 1.00-1.73) and combined p21 98AC/AA (OR = 1.37, 95% CI = 1.05-1.79) genotypes. When these two polymorphisms were evaluated together by the number of risk alleles, there was a significant increase in SCCHN risk that was dependent on the number of risk alleles (P(trend) = 0.001). Our results suggest that the presence of these two p21 polymorphisms may be a marker of genetic susceptibility to SCCHN.

3' Untranslated Regions↗

PubMed2005

Dinucleotide polymorphism of p73 gene is associated with a reduced risk of lung cancer in a Chinese population.

p73, a structural and functional homologue of p53, shares some p53-like tumor suppressor activity but also possesses oncogenic activity. Therefore, p73 plays an important role in modulating cell-cycle control and apoptosis. A potentially functional dinucleotide polymorphism, G4C14-to-A4T14, has been identified in the 5' untranslated region (UTR) of exon 2 of the p73 gene, which may theoretically form a stem-loop structure and affect gene expression. To test the hypothesis that these 2 common variants play a role in lung cancer susceptibility, we conducted a case-control study of 425 lung cancer patients and 588 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population. The results showed that these 2 polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less common in the cases (0.225) than in the controls (0.287) (p = 0.0018), suggesting that this AT haplotype was protective against lung cancer. Compared to the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk (adjusted OR: 0.45, 95% CI: 0.26-0.80 and OR: 0.70, 95% CI: 0.53-0.92, respectively). These results suggest that this p73 dinucleotide polymorphism may have a role in lung cancer susceptibility in our study population. Further studies are needed to elucidate potential functional relevance of the p73 AT variant allele.

Aged↗

PubMed2005

Plasma antibodies against heat shock protein 70 correlate with the incidence and severity of asthma in a Chinese population.

BACKGROUND: The heat shock proteins (Hsps) are induced by stresses such as allergic factors and inflammatory responses in bronchi epithelial cells and therefore may be detectable in patients with asthma. However, the etiologic link between anti-Hsps and asthma (its severity and related inflammatory responses such as interleukin-4 and immunoglobulin E) has not been established. We determined whether antibodies against Hsp60 and Hsp70 were present in patients with asthma and evaluated their associations with risk and severity of asthma. METHODS: We determined the levels of anti-Hsp60 and anti-Hsp70 by immunoblot and their associations with risk and symptom severity of asthma in 95 patients with asthma and 99 matched non-symptomatic controls using multivariate logistic regression analysis. RESULTS: Compared to the controls, asthma patients were more likely to have detectable anti-Hsp60 (17.2% vs 5.1%) and anti-Hsp70 (33.7% vs 8.1%) (p < or = 0.001). In particular, the presence of anti-Hsp70 was associated with a greater than 2 fold risk for asthma (adjusted OR = 2.21; 95% CI = 1.35 approximately 3.59). Furthermore, both anti-Hsp60 and anti-Hsp70 levels were positively correlated with symptom severity (p < 0.05) as well as interleukin-4 and immunoglobulin E (p < 0.05). Individuals with antibodies against anti-Hsp60 and anti-Hsp70 were more likely to have a family history of asthma (p < 0.001) and higher plasma concentrations of total immunoglobulin E (p = 0.001) and interleukin-4 (p < 0.05) than those without antibodies. CONCLUSIONS: These data suggest that anti-Hsp60 and especially anti-Hsp70 correlate with the attacks and severity of asthma. The underlying molecular mechanisms linking antibodies to heat shock proteins and asthma remain to be investigated.

Adolescent↗

PubMed2005

Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer.

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier.

Aged↗

PubMed2005

A pilot study of Helicobacter pylori infection and risk of laryngopharyngeal cancer.

BACKGROUND: Squamous cell carcinoma of the laryngopharynx has been linked to laryngopharyngeal reflux disease. Helicobacter pylori corpus gastritis decreases gastric acid secretion and provides some protection against complications of gastroesophageal reflux, including adenocarcinoma of the distal esophagus. The aim of this study was to investigate whether H. pylori infection also protects against laryngopharyngeal carcinoma. METHODS: This was a case-control study comparing patients with histologically confirmed, previously untreated laryngeal or pharyngeal squamous cell carcinomas with cancer-free controls selected from a pool of hospital-based cancer-free controls identified during a similar time period. Each subject completed a self-administered questionnaire that elicited information on age, sex, ethnicity, and tobacco and alcohol consumption. The 120 case subjects were frequency matched to 120 control subjects on age (+/- 5 years), sex, tobacco use, and alcohol use; all subjects were non-Hispanic whites. H. pylori and human papillomavirus type 16 (HPV-16) seropositivity was determined by use of an enzyme-linked immunosorbent assay. RESULTS: The serologic assay was unsuccessful in one case subject and nine control subjects; therefore, 119 case subjects and 111 control subjects were included in the analysis. The proportion of subjects with anti-H. pylori immunoglobulin G was similar between the two groups (32.8% among cases vs 27.0% among controls; p = .342). Although seropositivity was more common in the patients with laryngeal cancer (39.1%) than in the patients with pharyngeal cancer (28.8%), this difference was neither significant (p = .241) nor associated with a significant risk of laryngeal cancer (adjusted odds ratio, 1.53; 95% confidence interval, 0.69-3.41). H. pylori seropositivity was more common among patients who were HPV-16 seronegative (38.2% vs 22.9%, p = .081), and this was particularly true among patients with laryngeal cancer (47.1% vs 18.2%; p = .089). CONCLUSIONS: These results do not show that H. pylori infection either protects against or promotes laryngopharyngeal carcinoma. However, segregation analyses suggested that H. pylori may play a role in laryngeal cancers not associated with HPV-16 infection, and further study in this group is warranted.

Aged↗

PubMed2005

Nucleotide excision repair as a marker for susceptibility to tobacco-related cancers: a review of molecular epidemiological studies.

DNA repair is a complicated biological process consisting of several distinct pathways that play a central role in maintaining genomic stability. Research on DNA repair and cancer risk is a vital, emerging field that recently has seen rapid advances facilitated by the completion of the Human Genome Project. In this review, we described phenotypic and genotypic markers of nucleotide excision repair (NER) that have been used in molecular epidemiology studies. We summarized the population-based studies to date that have examined the association between DNA repair capacity phenotype and genetic polymorphisms of the NER genes and risk of tobacco-related cancers, including cancers of the lung, head and neck, prostate, bladder, breast, and esophagus. We also included studies of melanoma and nonmelanoma skin cancers because individuals with defective NER, such as patients with xeroderma pigmentosum (XP) are highly susceptible to ultraviolet light (UV)-induced melanoma and nonmelanoma skin cancers. The published data provide emerging evidence that DNA repair capacity may contribute to genetic susceptibility to cancers in the general population. However, many of the studies are limited in terms of the size of the study populations. Furthermore, all published findings are still considered preliminary, the assays used in the studies have yet to be validated, and the results need to be confirmed. Large and well-designed population-based studies are warranted to assess gene-gene and gene-environment interactions and to ultimately determine, which biomarkers of DNA repair capacity are useful for screening high-risk populations for primary prevention and early detection of tobacco-related cancers.

Biomarkers, Tumor↗

PubMed2005

A pilot case-control study of gamma-radiation sensitivity and risk of papillary thyroid cancer.

In vitro gamma-radiation-induced chromatid breaks per cell (b/c) in lymphocytes may be associated with risk of papillary thyroid cancer (PTC). This pilot case-control study involved 106 patients with thyroid disease (57 with PTC and 49 with benign thyroid disease) and 105 cancer-free matched controls. Multivariate logistic regression analyses identified that an elevated gamma-radiation-induced b/c value was a risk factor for PTC (adjusted odds ratio = 4.54; 95% CI, 2.07-9.95), and a dose-response relationship was evident when the b/c values were categorized into tertiles. High levels of chromatid breaks induced by gamma-radiation may constitute an independent risk factor for PTC, but further study is needed.

Adolescent↗

PubMed2005

A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk of lung cancer in relation to tobacco smoking.

X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base-excision repair pathway. Functional Polymorphisms in the XRCC1 gene may lead to decreased DNA repair capacity and thus confer inherited predisposition to cancer risk. In this case-control study of 710 patients with incident lung cancer and 710 cancer-free controls who were frequency matched on age, sex and residential area, we genotyped a novel T>C transition at the promoter region (-77T>C) of XRCC1 and other two common non-synonymous polymorphisms (Arg194Trp and Arg399Gln) to determine their associations with risk of lung cancer. We found that compared with the -77TT wild-type homozygote, the variant genotypes were associated with significantly increased risk of lung cancer [adjusted odds ratio (OR)=1.51; 95% confidence interval (CI)=1.17-1.94 for -77TC; OR=2.98; 95% CI=0.93-9.59 for -77CC; and OR=1.55; 95% CI=1.21-1.98 for -77TC/CC]. By contrast, no significant associations were observed between the other two exonic variants (Arg194Trp and Arg399Gln) and lung cancer risk. Furthermore, we observed a 9.82-fold increased risk (95% CI=5.66-17.02) for heavy smokers carrying the -77C variant (-77TC/CC) and a 4.07-fold increased risk (95% CI=2.85-5.81) for heavy smokers not carrying the variant. However, the interaction between the -77T>C variant and cumulative smoking was not statistically significant (P=0.1560). These findings indicate that the new XRCC1 -77T>C polymorphism may contribute to the aetiology of lung cancer. Further functional studies are warranted to elucidate the underlying molecular mechanisms of the association.

Adenocarcinoma↗

PubMed2005

Polymorphisms and haplotypes of serine hydroxymethyltransferase and risk of squamous cell carcinoma of the head and neck: a case-control analysis.

Low dietary intake of fruits and vegetables, particularly folate deficiency, has been associated with the risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that polymorphisms of the cytosolic serine hydroxymethyltransferase (SHMT1) gene involved in folate-dependent, one-carbon metabolism are associated with SCCHN risk. In a hospital-based, case-control study of 721 non-Hispanic white SCCHN patients and 1,234 control subjects, frequency-matched by age and sex, three known SHMT1 polymorphisms (34761C>T, 34840C>G and 34859C>T) were genotyped. It was found that none of these three polymorphisms alone had a significant main effect on the risk of SCCHN. However, when the three polymorphisms were evaluated together by the number of the variant (risk) haplotype alleles (i.e. 34761 T, 34840G or 34859 T), the risk of SCCHN was significantly increased in a dose-response manner as the number of variant haplotype alleles increased compared to those with zero variant alleles [adjusted odd ratio (OR)=1.39, 95% confidence interval (CI)=1.14-1.70 for 1-3 variant alleles and OR=1.46, 95% CI=1.09-1.97 for 4-6 variant alleles; Ptrend=0.001]. In stratification analysis, this significant association was confined to younger men (<or=64 years), ever smokers, ever drinkers and patients whose primary tumor site was in the pharynx or larynx. In conclusion, these three SHMT1 polymorphisms may play a joint role in the etiology of SCCHN in a non-Hispanic white population.

Aged↗

PubMed2005

Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer: a case-control analysis.

Although tobacco is the major lung cancer risk factor, folate deficiency has also been implicated as a risk. Methionine synthase (MS; gene symbol, MTR) and methionine synthase reductase (MSR; gene symbol, MTRR) play important roles in the folate metabolism pathway. It was hypothesized that polymorphisms of MTR and MTRR are associated with lung cancer risk and interact with dietary intake of folate-related nutrients in lung cancer etiology. In a hospital-based, case-control study of 1,035 lung cancer cases and 1,148 controls of non-Hispanic whites, frequency matched by age, sex, ethnicity and smoking status, the MTR 2756A>G and MTRR 66A>G polymorphisms were genotyped. It was found that the MTRRG allele was associated with a significantly increased lung cancer risk [adjusted odd ratio (OR)=1.34, 95% confidence interval (CI)=1.06-1.70 for the AG genotype and OR=1.39, 95% CI=1.08-1.78 for the GG genotype compared to the AA genotype]. Further analysis suggested some evidence of gene-diet interactions between the MTRR 66A>G polymorphism and dietary intake of total folate and vitamin B12. When the two polymorphisms were evaluated together by the number of the variant alleles (i.e. the MTR2756G and MTRR66A), lung cancer risk was significantly increased in a dose-dependent manner (Ptrend=0.045). The risk of lung cancer was 1.29 (0.98-1.69) for one variant allele, and 1.36 (1.04-1.77) for two or more variant alleles compared to the wild-type (0 variant allele) genotype. In conclusion, our data provide evidence supporting the association between the MTR 2756A>G and MTRR 66A>G polymorphisms and lung cancer risk, which may be modulated by dietary nutrient intake.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2005

RET polymorphisms and haplotypes and risk of differentiated thyroid cancer.

OBJECTIVE: To determine whether common (allele frequencies > 5%) single nucleotide polymorphisms located in exons 2, 7, 11, 13, 14, and 15 of the RET proto-oncogene are associated with risk of differentiated thyroid carcinoma (DTC). STUDY DESIGN: Hospital-based case-control study. METHODS: Patients with DTC or benign thyroid disease (BTD) were frequency matched with cancer-free controls on age and sex. Only non-Hispanic whites were included to avoid racial confounding. Polymerase chain reaction-restriction fragment-length polymorphism assays were used for genotyping. Multivariate logistic regression analysis was performed to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Haplotype distributions were estimated using Bayesian analyses. RESULTS: DTC cases and controls had similar rates of tobacco, alcohol, and radiation exposure. The genotype distributions were similar between DTC cases (n = 101) and controls (n = 174) except for RET 7 and RET 14 (P = .003 and P = .047, respectively) and between BTD cases (n = 62) and controls except for RET 14 (borderline; P = .064). Polymorphic allele frequencies were similar between the cases and controls except for RET 14 (borderline; P = .051 and P = .068 for DTC and BTD, respectively). The RET 7 heterozygous polymorphic genotype was associated with a significantly increased risk of DTC after multivariate adjustment (OR = 2.0, 95% CI = 1.2-3.4, P = .012). Compared with the most common haplotype (GGGTCC), no RET haplotype was associated with a significantly increased risk of DTC. CONCLUSIONS: Exon 7 (and possibly 14) polymorphism of RET may be associated with increased risk of DTC. However, the sample size is relatively small, and larger investigations are needed.

Female↗