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Biomedical subjects

Wen Tan

Publications and source records attributed to Wen Tan.

At least 55 records · Page 3Linked to original sources
PubMed2004

Functional STK15 Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal squamous cell carcinoma.

STK15/BTAK/Aurora-A involved in regulating centrosomes and chromosome segregation is amplified and overexpressed in human cancers. A T91A polymorphism in STK15 causes Phe31Ile substitution, and the 31Ile variant has been shown to be preferentially amplified and associated with degree of aneuploidy in human tumors. We genotyped 656 patients with esophageal squamous cell carcinoma (ESCC) and 656 controls for the polymorphism to examine the hypothesis that the STK15 variation may affect individual susceptibility to the occurrence and aggression of ESCC. It was found that the Ile/Ile genotype was significantly associated with increased risk of ESCC occurrence [odds ratio (OR) = 1.97, 95% confidence interval (CI) = 1.36-2.85] compared with the Phe/Phe genotype. The 31Ile allele frequency significantly increased as ESCC stage increased (trend test, P = 0.006). Patients with the Ile/Ile genotype had an increased risk for invasive disease (stage II-IV; OR = 2.13, 95% CI = 1.04-4.39) or metastatic disease (stage III and IV; OR = 2.31, 95% CI = 1.06-5.05) compared with those with the Phe/Phe genotype. A positive correlation between the Ile/Ile genotype and high ESCC grade was also observed. Our results demonstrate for the first time that the STK15 polymorphism is a genetic susceptibility factor for the occurrence and aggression of ESCC.

Aurora Kinase A↗
PubMed2004

Short tandem repeat polymorphism in a novel esophageal cancer-related gene (ECRG2) implicates susceptibility to esophageal cancer in Chinese population.

We have previously cloned and identified a novel esophageal cancer related gene 2 (ECRG2; GenBank Accession Number AF268198), which is down-regulated in esophageal squamous cell carcinoma (ESCC) and involved in the induction of the apoptosis in esophageal cancer cell lines. In the present study, we have found a short tandem repeat (STR) polymorphism in the noncoding region of the exon 4 of the ECRG2 gene by using PCR-denaturing high-performance liquid chromatography (DHPLC). Three STR genotypes, TCA3/TCA3, TCA3/TCA4 and TCA4/TCA4 were revealed and confirmed by DNA sequencing analysis. A total of 661 objects including 228 patients with ESCC and 373 normal controls were analyzed to investigate the impact of this ECRG2 STR polymorphism on risk of ESCC in case-control studies. Genotypes were determined in 231 controls and 162 cases from Beijing, which is a low risk area of ESCC, and in 142 controls and 126 cases from Linxian, a well-known high-risk area of ESCC. In both of the Beijing and Linxian population, subjects who carried the TCA3/TCA3 genotype were at an increased risk of ESCC compared to those carrying the TCA4/TCA4 genotype, with the adjusted odds ratios (ORs) being 2.05 [95% confidence interval (CI), 1.02-4.06] for the subjects from Beijing and 4.40 (95% CI, 1.93-10.01) for the subjects from Linxian. Furthermore, comparison of the genotype distributions among other cancer sites might suggest that risk of the ECRG2 STR polymorphism might be specific to the esophagus. These findings indicate for the first time that the ECRG2 STR is a genetic susceptibility factor for ESCC and the TCA3/TCA3 allele might play a role in the development of this cancer.

Aged↗
PubMed2004

Tuning of PID controllers for boiler-turbine units.

A simple two-by-two model for a boiler-turbine unit is demonstrated in this paper. The model can capture the essential dynamics of a unit. The design of a coordinated controller is discussed based on this model. A PID control structure is derived, and a tuning procedure is proposed. The examples show that the method is easy to apply and can achieve acceptable performance.

Journal Article↗
PubMed2004

[Single nucleotide polymorphisms in XRCC1 and clinical response to platin-based chemotherapy in advanced non-small cell lung cancer].

BACKGROUND & OBJECTIVE: DNA repair capacity correlated with sensitivity of cancer cells towards platin-based chemotherapy. This study examined the association between genetic polymorphisms of DNA repair gene XRCC1 and response to cisplatin- or carboplatin-based chemotherapy of advanced non-small cell lung cancer (NSCLC). METHODS: Totally 105 patients with advanced NSCLC were routinely treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. XRCC1 genotypes were determined by PCR-RFLP methods using DNA samples isolated from peripheral blood collected before treatment. The odds ratios (ORs) and 95% confidence intervals (CIs) were computed by logistic regression. RESULTS: The response rate to the chemotherapy in patients with the 194Arg/Trp or Trp/Trp genotype significantly higher than that in patients with the Arg/Arg genotype (43.1% vs. 20.3%;OR=2.97,95% CI=1.15-7.72;P< 0.05). The response rate to chemotherapy was also significantly higher in patients with the 399Arg/Arg genotype than that in patient with the Arg/Gln or Gln/Gln genotype (41.5% vs. 21.2%;OR=2.65,95% CI=1.03-6.87;P< 0.05).Furthermore, it appeared that 194Arg/Trp and 399Arg/Arg genotypes had synergic effect on the chemotherapy efficacy. Patients with both of these two polymorphisms had a response rate of 66.7% which was significantly greater than that in patients with other genotypes (response rate ranging from 20.0% to 23.1%, P< 0.001). CONCLUSION: Polymorphisms in the XRCC1 gene may have significant impact on the response of NSCLC patients to platin-based chemotherapy.

Adult↗
PubMed2004

[Association between genetic polymorphisms in methylenetetrahydrofolate reductase and risk of breast cancer].

OBJECTIVE: To investigate the association between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and risk of breast cancer among women. METHODS: Two hundred seventeen cases with breast cancer and 218 matched controls were genotyped for the MTHFR C677T and A1298C polymorphisms by PCR-RFLP methods. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. RESULTS: We found that the frequency of the MTHFR C677TT genotype among cases was significantly different from that among controls (32.7% vs. 24.8%; P = 0.02). The MTHFR C677TT genotype had an increased risk of breast cancer compared with the 677CC genotype (95% CI, 1.09 - 3.14). No significant association between the MTHFR C677T or A1298C polymorphism and risk of the cancer was observed. CONCLUSION: These findings suggest that 677CT polymorphism in MTHFR may be a genetic susceptibility factor for breast cancer among Chinese women.

Asian People↗
PubMed2004

[Association of functional polymorphisms in matrix metalloproteinase-2 (MMP-2) and MMP-9 genes with risk of gastric cancer in a Chinese population].

BACKGROUND & OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play important roles in the development of gastric cancer. This study was to investigate the association of functional polymorphisms in the MMP-2 and MMP-9 genes with risk of gastric cancer in a Chinese population. METHODS: MMP-2 -1306T/C,and MMP-9 -1562C/T polymorphisms in 228 patients with gastric cancer, and 774 matched healthy controls were detected by polymerase chain reaction (PCR)-based denaturing high performance liquid chromatography, and PCR-based restriction fragment length polymorphism analysis. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. The effect-modified model was used to evaluate the gene-gene interaction. RESULTS: Subjects with the MMP-2 -1306CC genotype had an increased risk of developing gastric cancer compared with those with the MMP-2 -1306TT or CT genotype (adjusted OR, 1.67; 95% CI, 1.17-2.38). No significant association between MMP-9 -1562C/T polymorphism and risk of gastric cancer was observed. However, the polymorphisms in these 2 genes seem to display a gene-gene interaction, with OR of 1.72 (95% CI, 1.07-2.78) for subjects carrying both MMP-2 -1306CC and MMP-9 -1562TT or CT genotypes compared with those carrying both MMP-2 -1306TT or CT and MMP-2 -1306T/C genotypes (likelihood ratio test, P=0.02). CONCLUSION: MMP-2 -1306T/C and MMP-9 -1562C/T polymorphisms may be associated with genetic susceptibility to gastric cancer.

Adult↗
PubMed2003

A functional polymorphism in the SULT1A1 gene (G638A) is associated with risk of lung cancer in relation to tobacco smoking.

Sulfotransferase 1A1, an important member of sulfotransferase superfamily, is involved in the biotransformation of many compounds including tobacco carcinogens. A single nucleotide polymorphism (G638A) in the sulfotransferase 1A1 (SULT1A1) gene causes Arg213His amino acid change and consequently results in significantly reduced enzyme activity and thermostability. We thus hypothesized that the variant SULT1A1 allele may protect against the risk of lung cancer related to tobacco smoking. To examine this hypothesis, we analyzed 805 patients with lung cancer and 809 controls for this polymorphism in a hospital-based, case-control study. We observed that, compared with the GG genotype, the variant SULT1A1 genotype (638GA or AA) was associated with a significantly increased risk for overall lung cancer [odds ratio (OR) 1.85; 95% confidence interval (CI) 1.44-2.37]. Stratification analysis showed that the increased risk of lung cancer related to the variant SULT1A1 genotypes was more pronounced in younger subjects and limited to smokers but not non-smokers [OR 2.28 (95% CI 1.66-3.13) versus OR 1.35 (95% CI 0.91-1.99); P for homogeneity = 0.000]. Furthermore, the risk of lung cancer for the variant genotypes was increased consistently with cumulative smoking dose, with the ORs being 1.66 (95% CI, 0.75-3.68), 2.28 (95% CI, 1.47-3.54) and 3.35 (95% CI, 1.71-6.57) for those who smoked <15 pack-years, 15-36 pack-years and >36 pack-years, respectively (P for trend = 0.000). When analysis was stratified by histological subtypes of lung cancer, consistent results were observed for all three major types of the cancer, i.e. squamous cell carcinoma, adenocarcinoma and other types. Our results, which are against the original hypothesis, demonstrate that the variant SULT1A1 638A allele is associated with susceptibility to lung cancer in relation to tobacco smoking.

Adenocarcinoma↗
PubMed2003

Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK.

Cytochrome P450 2A13 (CYP2A13), an enzyme expressed predominantly in the human respiratory tract, exhibits high efficiency in the metabolic activation of tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). A C-->T transition in the CYP2A13 gene causes Arg257Cys amino acid substitution and, thus, results in a significantly reduced activity toward NNK and other substrates. In this case-control study, we genotyped 724 patients with lung cancer and 791 controls for this polymorphism to examine the hypothesis that the variant CYP2A13 may have impact on risk of lung cancer in relation to tobacco smoking. A gene deletion polymorphism (CYP2A6*4) in CYP2A6, another enzyme involved in the metabolic activation of tobacco nitrosamines, was also analyzed as a comparison. We found that, compared with the CC genotype, the variant CYP2A13 genotype (CT + TT) was associated with substantially reduced risk for lung adenocarcinoma [odds ratio (OR), 0.41; 95% confidence interval (CI), 0.23-0.71], but not squamous cell carcinoma (OR, 0.86; 95% CI, 0.57-1.29) or other types of lung cancer (OR, 0.58; 95% CI, 0.32-1.09). Stratification analysis shows that the reduced risk of lung adenocarcinoma related to the variant CYP2A13 genotype was limited to smokers, especially light smokers (OR, 0.23; 95% CI, 0.08-0.68) but not nonsmokers or heavy smokers. No association was observed between CYP2A6 genotype and risk of lung cancer. Our results demonstrate for the first time that the variant CYP2A13 allele is associated with reduced risk of lung adenocarcinoma, suggesting the role of NNK-CYP2A13 interaction as a causative factor for the cancer.

Adenocarcinoma↗
PubMed2003

Substantial reduction in risk of breast cancer associated with genetic polymorphisms in the promoters of the matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 genes.

The matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) have been shown to play important roles in multiple ways in all stages of cancer initiation and development. Single nucleotide polymorphisms identified in the promoters of MMP2 (-1306C-->T) and TIMP2 (-418G-->C) abolish the Sp1-binding site and thus may down-regulate expression of the genes. This case-control study examined the contribution of these functional polymorphisms to susceptibility to development and metastasis of breast cancer. MMP2 genotypes were determined by PCR-based denaturing high performance liquid chromatography analysis and TIMP2 genotypes identified by a PCR-RFLP method in 462 breast cancer patients and 509 frequency matched control women. We found that the variant MMP2 genotype (-1306CT or TT) was associated with substantially reduced risk of breast cancer [odds ratio (OR), 0.46; 95% confidence interval (95% CI), 0.34-0.63], compared with the CC genotype. For TIMP2, a moderately reduced risk of the cancer (OR, 0.76; 95% CI, 0.58-0.99) was also associated with the variant allele (-418GC or CC), compared with the GG common allele. Furthermore, it seemed that the polymorphisms in the two genes had some additive effect and the reduced risk related to the polymorphisms appeared to be more pronounced in younger subjects. However, no significant associations were observed between the polymorphisms in the two genes and tumor stage and metastasis of the cancer at the time of diagnosis. These findings suggest that the presence of the variant allele in the promoter of MMP2 or TIMP2 may be a protective factor for the development of breast cancer.

Adult↗
PubMed2003

A functional polymorphism in the matrix metalloproteinase-2 gene promoter (-1306C/T) is associated with risk of development but not metastasis of gastric cardia adenocarcinoma.

Matrix metalloproteinase-2 (MMP-2) has been shown to play an importantrole in multiple ways to all stages of cancer initiation and development.We have reported previously a strong association between a functional single nucleotide polymorphism (-1306C/T) in the MMP2 promoter and risk of lung cancer (C. Yu et al., Cancer Res., 62: 6430-6433, 2002). This case control study was to assess the contribution of this MMP2 polymorphism to risk of development and metastasis of gastric cardia adenocarcinoma (GCA). MMP2 genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 356 patients with GCA and 789 frequency-matched controls in an ethnic Chinese population. We found that subjects with the CC genotype had >3-fold increased risk [adjusted odds ratio 3.36, 95% confidence interval 2.34-4.97] for developing GCA compared with those with the variant CT or TT genotype. Furthermore, the increased risk was found to be more pronounced in smokers and younger subjects. However, no significant association was demonstrated between the MMP2 polymorphism and risk of metastasis of the cancer at the time of diagnosis, with the odds ratio being 0.90 (95% confidence interval 0.36-2.20) for the CC genotype. These findings are consistent with our initial observation for lung cancer and further support the hypothesis that MMP2 genotype may influence individual susceptibility to the development of certain cancer.

Adenocarcinoma↗
PubMed2003

Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population.

Variation in DNA repair capacity, which is believed to be largely determined by genetic traits, is linked to risk of certain cancers. The Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may alter DNA repair capacity. We thus examined the hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer via a large hospital-based, case-control study among Chinese. The study subjects consisted of 1,006 patients with primary lung cancer and 1,020 age- and sex-matched population controls. XPD genotypes were determined using PCR-RFLP techniques, and the associations between genotypes and risk of lung cancer were estimated by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated by unconditional logistic regression. Subjects homozygous for the 312Asn/Asn genotype had an increased risk of lung cancer (adjusted OR = 10.33, 95% CI = 1.29-82.50) compared with subjects homozygous for the 312Asp/Asp genotype. The 751Gln/Gln genotype was also associated with increased risk for the cancer compared with the 751Lys/Lys genotype (adjusted OR = 2.71, 95% CI = 1.01-7.24). Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the ORs being 20.50 (95% CI = 2.25-179.05) for the 312Asn/Asn genotype and 4.24 (95% CI = 1.34-13.38) for the 751Gln/Gln genotype, respectively. Haplotype analysis with the 2 polymorphisms suggested these polymorphisms might be in linkage disequilibrium with a different causative locus or act together with other functional variants in or close to the XPD locus.

Aged↗
PubMed2003

Inactivation of DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation and its relation to p53 mutations in esophageal squamous cell carcinoma.

The development of esophageal squamous cell carcinoma (ESCC) has been linked to exposure to carcinogens such as nitrosamines that cause various alkyl DNA damages and O6-methylguanine-DNA methyltransferase (MGMT) is a primary defence against alkylation-induced mutagenesis and carcinogenesis. This study was to investigate the role of inactivation of MGMT by promoter hypermethylation and its relation to p53 mutations in ESCC. Methylation of MGMT promoter was determined by methylation-specific polymerase chain reaction in 119 ESCC specimens, 22 corresponding tissue samples adjacent to the tumors, and 21 normal epithelial specimens of the esophagus. The levels of MGMT protein in ESCC with methylated or unmethylated MGMT were analyzed by quantitative immunohistochemistry. Mutations of p53 in 119 ESCC were detected by denaturing high-performance liquid chromatography and sequencing. We found that all 21 normal esophageal tissues had unmethylated MGMT; however, among 119 ESCC, 46 (38.7%) had hypermethylated MGMT. This epigenetic change also occurred in some normal tissues adjacent to the tumors. The level of MGMT protein in MGMT-methylated ESCC was significantly lower than that in MGMT-unmethylated ESCC, whereas great inter-individual variation and poor expression was also observed among MGMT-unmethylated ESCC. Fifty-one percent (61/119) ESCC showed p53 mutations but the distribution of the mutations did not differ significantly between MGMT-methylated ESCC (44%) and MGMT-unmethylated ESCC (56.2%; P = 0.18). MGMT promoter hypermethylation was neither associated with overall G:C to A:T mutations nor associated with this type of mutations in non-CpG dinucleotides in p53. Our results demonstrate that inactivation of MGMT by aberrant promoter methylation is a frequent molecular event in ESCC. This epigenetic alteration is an important, but may not be the sole, mechanism leading to the impaired expression of MGMT. Aberrant MGMT methylation seemed not to be associated with overall frequency and spectrum of p53 mutations in ESCC.

Carcinoma, Squamous Cell↗
PubMed2003

[Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing].

OBJECTIVE: XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study. METHODS: Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. RESULTS: Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0.55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smoking>or=29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found. CONCLUSION: The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.

Adenocarcinoma↗
PubMed2003

[Relation between single nucleotide polymorphism in estrogen-metabolizing genes COMT, CYP17 and breast cancer risk among Chinese women].

OBJECTIVE: To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women. METHODS: COMT (Val158Met) and CYP17 (T1931C) polymorphisms were detected by PCR-based restriction fragment length polymorphism analysis in 250 breast cancer patients and 250 frequency-matched normal controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression. RESULTS: COMT Met/Met genotype was found in 10.4% of breast cancer patients, which was significantly higher (P = 0.03) than that in controls (5.2%). Women with Met/Met genotype showed 2-fold increased risk for breast cancer (adjusted OR 2.1, 95% CI 1.1 - 4.5) compared with those with Val/Val or Val/Met genotypes. Stratified analysis showed that the elevated risk of breast cancer, associating with the COMT Met/Met genotype, was evident only among premenopausal women (adjusted OR 4.1, 95% CI 1.2 - 17.3) but not among postmenopausal women (adjusted OR 1.3, 95% CI 0.5 - 3.5). There was no significant difference in the distribution of CYP17 genotypes between breast cancer patients and the control subjects (P = 0.83). CONCLUSION: The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.

Adult↗
PubMed2003

[Poly(AT) polymorphism in DNA repair gene XPC and lung cancer risk].

OBJECTIVE: It has been shown that suboptimal DNA repair capacity is associated with cancer risk and that a poly(AT) polymorphism in XPC gene (XPC PAT) may influence DNA capacity. This study was designed to assess the relationship between XPC PAT polymorphism and susceptibility to lung cancer in the Chinese population. METHODS: XPC genotypes were determined by PCR methods in 509 healthy controls and 597 patients with lung cancer. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression model. RESULTS: Genotype frequencies of XPC PAT among controls were 37.9% (PAT-/-), 49.7% (PAT+/-) and 12.4% (PAT+/+), respectively. They were not significantly different from those among lung cancer patients (42.1%, 46.7% and 11.2%, respectively; P = 0.37). Individuals carrying XPC PAT+/+ genotype were not at increased risk for lung cancer as compared with those with PAT+/- or PAT-/- genotype (adjusted OR, 0.8; 95% CI, 0.55 approximately 1.16). No interaction between XPC genotype and smoking was observed. CONCLUSION: Our findings indicate that the XPC PAT polymorphism may not be associated with risk of lung cancer in the Chinese population.

Adult↗
PubMed2002

Genetic polymorphism in myeloperoxidase but not GSTM1 is associated with risk of lung squamous cell carcinoma in a Chinese population.

Myeloperoxidase (MPO), an enzyme derived from neutrophils, metabolically activates a wide range of carcinogens, whereas glutathione S-transferase M1 (GSTM1) detoxifies various electrophilic metabolites. A -463G-->A polymorphism in the promoter region of the MPO gene diminishes the expression of MPO and has been consistently shown to be associated with reduced risk of lung cancer in different ethnic populations. In our study, we have assessed the role of this polymorphism in lung cancer risk in a Chinese population. Genotypes of MPO and GSTM1 were determined by PCR-SSCP and multiplex PCR in 314 patients with lung cancer and 320 frequency-matched controls. The allele frequency for MPO -463A was found to be 0.155 in controls and 0.114 in cases. Subjects with the MPO -463GG genotype were at an increased risk of squamous cell carcinoma (SCC) of the lung compared to those having at least one -463A variant allele (adjusted odds ratio [OR] 2.35; 95% confidence interval [CI] 1.40-3.94). Stratified analysis suggested an interaction between heavy smoking (> or =26 pack-years) and the MPO-463GG genotype. The adjusted OR of lung SCC for those having MPO-463GG genotype and smoked > or =26 pack-years was 20.50 (95% CI 5.58-75.33) compared to 6.22 (95% CI 1.72-22.47) for those smoked > or =26 pack-years but having at least one variant A allele (p = 0.023, test for homogeneity). This effect of the MPO polymorphism was not observed in lung adenocarcinoma. GSTM1 deletion was quite common in both controls (49.4%) and cases (50.3%) but was not associated with risk of lung cancer alone or in combination with the MPO polymorphism. Our results confirm the previous reports showing that the variant A allele of MPO has a protective effect against risk of lung cancer.

Alleles↗
PubMed2002

Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer.

Matrix metalloproteinases (MMPs) play an important role in several steps of cancer development. A single nucleotide polymorphism (-1306C-->T) in the MMP2 promoter sequence disrupts an Sp1 site and thus results in strikingly lower promoter activity. We examined the relationship between this polymorphism and risk for lung cancer in 781 cases and 852 age- and sex-matched controls in a Chinese population. We found that the allele frequency of MMP2-1306C was significantly higher among cases than among controls (0.91 versus 0.83). Subjects with the CC genotype had an overall 2-fold increased risk for developing lung cancer [adjusted odds ratio (OR) 2.18; 95% confidence interval (CI), 1.70-2.79] compared with those with the CT or TT genotype. The elevated risk was observed evenly among different subtypes of this cancer. Stratified analysis indicated an additive interaction between the CC genotype and smoking on the elevated risk. The ORs of lung cancer for the CC genotype, smoking, and both factors combined were 2.38 (95% CI 1.64-3.45), 4.26 (95% CI 2.57-8.44), and 7.64 (95% CI 4.74-12.33), respectively. Furthermore, when the data were stratified by the pack-years smoked, this joint effect was more evident and stronger in heavy smokers (OR 10.25, 95% CI 5.80-18.09) than in light smokers (OR 5.55, 95% CI 3.34-9.22). These results demonstrate a significant association between the MMP2 -1306C/T polymorphism and risk of developing lung cancer solely or in a manner of interaction with carcinogen exposure.

Case-Control Studies↗