CYP2C19 polymorphism and clinical outcomes among patients of different races treated with clopidogrel: A systematic review and meta-analysis / 华中科技大学学报（医学）（英德文版）

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI). The primary outcome of our interest was the recurrence of major adverse cardiovascular events (MACE) in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

CYP2C19 polymorphism and clinical outcomes among patients of different races treated with clopidogrel: A systematic review and meta-analysis / 华中科技大学学报（医学）（英德文版）

Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI). The primary outcome of our interest was the recurrence of major adverse cardiovascular events (MACE) in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.

Epidemiological characteristics of influenza virus and respiratory syncytial virus among children in Wuhan area from 2008 to 2012 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the infection status and epidemiological characteristics of influenza virus and respiratory syncytial virus (RSV) in influenza-like illness (ILI) of children ( ≤ 14 years) in Wuhan area from 2008 to 2012.</p><p><b>METHODS</b>A total of 2854 cases of ILI patients ( ≤ 14 years) in a hospital of Wuhan were recruited in the study from July 2008 to June 2012. The sample of pharyngeal swab was collected from each patient, to extract the virus nucleic acids. Real-time fluorescent quantitation reverse transcription PCR (RT-PCR) method was applied to detect the subtypes of influenza virus and RSV, and then analyzed the time and age characteristics.</p><p><b>RESULTS</b>Out of the 2854 cases, 758 (26.6%) were positive for influenza virus,including 547 (19.2%) influenza A virus positive samples and 211 (7.4%) influenza B virus positive samples. Usually, there were two peaks present in the annual curve of influenza virus, namely summer peak and winter/spring peak. The positive rate of influenza virus in 6-14 years old children (48.0%, 275/573) was significantly higher than that in 3-5 years old children (26.6%, 213/801) and that under 3 years old children (18.3%, 270/1480). The difference showed statistical significance (χ(2) = 187.432, P < 0.01). A total of 219 (7.7%) cases were positive for RSV,including 108 RSV-A positive samples and 112 RSV-B positive samples (1 co-infection). The epidemic of RSV showed an obvious seasonal pattern with peaks in autumn,winter and spring,which accounted for 96.8% (212/219) of all the cases; however, the annual incidence of RSV fluctuated greatly. The predominant subtype shifted every 2 years. RSV-B predominated during September 2008 and May 2009, December 2009 and March 2010, accounting for 76.6% (36/47) and 96.9% (62/64) respectively. RSV-A predominated during November 2010 and March 2011, September 2011 and April 2012, accounting for 92.5% (37/40) and 100.0% (48/48) respectively. With the increase of the age, the positive rate of RSV-A and RSV-B decreased gradually (RSV-A: χ(2) = 36.223, P < 0.01; RSV-B: χ(2) = 36.281, P < 0.01). The positive rates of RSV-A in children < 1,1,2,3,4,5-9 and 10-14 years old were 7.0% (26/373), 5.9% (39/662), 4.0% (18/445), 3.2% (13/406), 1.3% (3/236), 1.4% (7/517) and 0.9% (2/215) respectively; while, the positive rates of RSV-B in each age group were 6.4% (24/373), 6.0% (40/662), 4.5% (20/445), 4.4% (18/406), 1.3% (3/236), 1.0% (5/517) and 0.9% (2/215) respectively. The children aged 0-3 years old were more susceptible for RSV infection,accounting for 90.0% (197/219) of the total positive samples. During the outbreak of influenza A H1N1 in November 2009, the positive rate of RSW was 3.0% (3/100), lower than that in the same month of 2008, 2010 and 2011,which were separately 18.2% (6/33), 10.8% (10/93) and 10.0% (4/40). The difference showed statistical significance (χ(2) = 8.450, P < 0.05). During the outbreak of influenza A (H1N1) in January 2011,the positive rate of RSV was 5.7% (3/53), lower than those in the same month of 2009, 2010 and 2012, which was separately 21.7% (5/23), 28.6% (22/77) and 16.0% (8/50). The difference showed statistical significance (χ(2) = 11.233,P < 0.05). During the period of less influenza happened in September 2011, the RSV positive rate was 25.0% (10/40), higher than those in the same month of 2008, 2009 and 2010, which was separately 11.4% (4/35), 1.7% (2/118) and 0.0% (0/109). The difference showed statistical significance (χ(2) = 32.521, P < 0.01).</p><p><b>CONCLUSION</b>Both influenza virus and RSV were important etiological agents of ILI of children in Wuhan. The characteristics of seasonal and age distributions of the two viruses were notably different; meanwhile, a certain inhibitional effect of influenza virus on RSV could be observed.</p>

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China / 癌症

Matrix metalloproteinase 2 (MMP2) has been shown to play an important role in several steps of cancer development. The -1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele, and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers. To assess the contribution of the MMP2 -1306C/T polymorphism to the risk of nasopharyngeal carcinoma (NPC), we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis. We found that subjects with the CC genotype had an increased risk (OR = 1.55, 95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes. Furthermore, we found that the risk of NPC was markedly increased in subjects who were smokers (OR = 15.04, 95% CI = 6.65-33.99), heavy smokers who smoked ≥ 20 pack-years (OR = 18.66, 95% CI = 7.67-45.38), or young (<60 years) at diagnosis (OR = 1.52, 95% CI = 1.01-2.29). Our results provide molecular epidemiological evidence that the MMP2 -1306C/T promoter polymorphism is associated with NPC risk, and this association is especially noteworthy in heavy smokers.

Genetic polymorphisms in the promoter region of cyclooxygenase-2 and their association with risk of gastric cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To examine the genetic polymorphisms in the promoter region of cyclooxygenase-2 ( COX-2) and evaluate their association with the risk of gastric cancer.</p><p><b>METHODS</b>Single-strand conformational polymorphism and DNA sequencing were used to screen the genetic variants of the COX-2 promoter region. Total 323 patients with gastric cancer and 646 frequency-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Haplotype frequency was estimated using Haplo. stat software.</p><p><b>RESULTS</b>Three single nucleotide polymorphisms, including - 1290A > G, -1195G > A, and -765G > C were identified in the promoter of COX- 2. Case-control analysis showed an increased risk of developing gastric cancer for the -1290AG (OR 1.64; 95% CI 1.03-2.61), -1195AA (OR 2.68; 95% CI 1.65-4.33), and -765CG (OR 2.66; 95% CI 1.53-4.64) genotype carriers, respectively, compared with noncarriers. A greater risk of developing gastric cancer was observed for the A(-1290) -A(-1195) -C(-765) haplotype compared with the A(-1290) -G(-1195) -G(-765) haplotypes (OR 11.80; 95% CI 2.43-57.25).</p><p><b>CONCLUSION</b>Genetic polymorphisms in COX-2 promoter region may play a role in gastric carcinogenesis.</p>

Study on the relations between genetic polymorphisms in methylenetetrahydrofolate reductase, methionine synthase and the risk of pancreatic cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine whether genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A2756G) were associated with the risks of pancreatic cancer.</p><p><b>METHODS</b>A hospital-based, case-control study consisting of 101 incident pancreatic cancer cases and 337 controls matched on age, sex and race was conducted to investigate the association between polymorphism in MTHFR and MS, and susceptibility to pancreatic cancer. Genotypes of MTHFR C677T, A1298C and MS A2756G were analyzed by polymerase chain reasction-restriction fragment length polymorphism methods.</p><p><b>RESULTS</b>It was found that multivariate-adjusted odds ratio (ORs; 95% confidence interval) for MTHFR-677CT and 677TT compared with 677CC were 2.17 (1.26 - 3.85) and 3.53 (1.85 - 6.84) respectively, which was in a manner of allele-dose relationship. However, no significant association between the A1298C genotype alone and the risk of cancer was observed which seemed that this polymorphism had a combined effect with the C677T polymorphism. A significant gene-environment interaction was observed between C677T polymorphism and cigarette smoking or alcohol intake. Subjects with variant genotypes who smoked > 17 pack-years had highest risk for developing the cancer, with the OR of 5.58 (2.53 - 12.30). Similarly, the OR (3.27, 1.51 - 7.23) for subjects with variant genotypes of alcohol drinker was significantly higher than that for subjects either having the variant genotype or being drinkers. No association was found between MS A2756G polymorphism and risk of pancreatic cancer in the study.</p><p><b>CONCLUSION</b>These findings supported the hypothesis that genetic polymorphisms in MTHFR C677T might contribute to the risk of developing pancreatic cancer.</p>

Association between genetic polymorphism in STK15 and risk of colorectal cancer in a Chinese population / 中华肿瘤杂志

<p><b>OBJECTIVE</b>This case-control study was designed to detect the association between STK15 Phe31Ile polymorphism and colorectal cancer.</p><p><b>METHODS</b>Genotypes were determined in 283 patients with colorectal cancer and 283 controls. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression model.</p><p><b>RESULTS</b>The frequency of the STK15 Ile/Ile genotype was significantly higher in cancer cases than in controls (50.2% vs. 36.8%; P = 0.02). Subjects with the Ile/Ile genotype had an increased risk for the occurrence of colorectal cancer compared with those with the STK15 Phe/Phe genotype (adjusted OR, 1.92; 95% CI, 1.13 - 3.27). No significant association was observed between this STK15 polymorphism and risk of metastasis of the cancer.</p><p><b>CONCLUSION</b>These findings suggest that STK15 Phe/Ile polymorphism may be a genetic susceptibility factor for colorectal cancer among Chinese.</p>

Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided.</p><p><b>RESULTS</b>The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively.</p><p><b>CONCLUSION</b>Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.</p>

XRCC1 and XPD genetic polymorphisms predict clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>DNA repair system plays an important role in tumor sensitivity to platinum-based chemotherapy. The purpose of this study was to examine the association between polymorphisms in XRCC1 and XPD, which are involved in DNA repair, and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>XRCC1 Arg194Trp and XPD Lys751Gln were genotyped by PCR-RFLP method in 200 patients with advanced NSCLC who received platinum-based chemotherapy. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses.</p><p><b>RESULTS</b>The overall response rate (CR + PR) was 36.0%, including 1 CR, 72 PR, 94 SD and 34 PD. The XRCC1 194Trp allele carriers had higher response rate than the subjects with the Arg/Arg genotype (adjusted OR, 2.48; 95% CI, 1.36 - 4.51, P = 0.003). However, the XPD Lys751Gln polymorphism was not found to be associated with the platinum-based chemotherapy. These two genetic polymorphisms may have some interaction in the drug sensitivity, the P value for the trend was significant (P = 0.004).</p><p><b>CONCLUSION</b>Those results suggest that the XRCC1 Arg194Trp and XPD Lys751Gln genetic polymorphisms may be associated with clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer.</p>

Association of two genetic polymorphisms in the 5'untranslated region of exon 2 of the p73 gene and risk of lung cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the relationship between two potential functional polymorphisms in exon 2 of the p73 gene and the susceptibility of lung cancer.</p><p><b>METHODS</b>Genotypes were determined by polymerase chain reaction-single stand conformation polymorphism (PCR-SSCP) method in 425 histologically-confirmed lung cancer cases and 588 cancer-free controls, frequency-matched by age and sex.</p><p><b>RESULTS</b>The two polymorphisms were in complete linkage disequilibrium and the frequencies of variant p73 AT haplotype (A4T14) were less commonly seen in the cases (0.225) than in the controls (0.287) (P = 0.0018). Compared with the p73 GC/GC homozygotes, both the AT/AT variant homozygotes and GC/AT heterozygotes were associated with a significantly decreased risk [adjusted odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26 - 0.80 and OR = 0.70, 95% CI = 0.53-0.92, respectively].</p><p><b>CONCLUSION</b>These results suggested that this p73 dinucleotide polymorphism might have had a role to play in the susceptibility of lung cancer.</p>

Association between genetic variations in methylenetetrahydrofolate reductase and risk of colorectal cancer in a Chinese population / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic variations in methylenetetrahydrofolate reductase (MTHFR) and the risk of colorectal cancer in a Chinese population.</p><p><b>METHODS</b>One hundred and ninety-eight cases of colorectal cancer and 420 controls were genotyped for detecting MTHFR C677T and A1298C polymorphisms by PCR-RFLP methods. The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by using unconditional logistic regression model.</p><p><b>RESULTS</b>The frequency of the MTHFR C677T allele found among cases was significantly more frequent than that among controls (51.3% to 44.4%, P = 0.02). As compared with the 677CC genotype, the 677TT genotypes had a 67% (95% CI, 1.05 - 2.66) increased risk of colorectal cancers. However, there appeared no any correlations between the genetic variations of MTHFR and the cancer metastasis.</p><p><b>CONCLUSION</b>These findings demonstrated that the genetic variation of MTHFR C677T should be a genetic susceptibility factor for colorectal cancer in a Chinese population.</p>

Association between genetic polymorphisms in methylentetrahydrofolate reductase and risk of lung cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the association between methylentetrahydrofolate reductase (MTHFR) polymorphisms and risk of lung cancer.</p><p><b>METHODS</b>Totally 505 cases with lung cancer and 500 frequency-matched controls were genotyped for the MTHFR C677T and A1298C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism methods. The odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression model. Haplotype frequency was estimated using EH software.</p><p><b>RESULTS</b>The frequency of the MTHFR C677T allele in cases was significantly higher than that in controls (53.5% vs 44.9%, P < 0.001). Compared with the 677CC genotype, the 677CT and 677TT genotypes were associated with increased risk of lung cancer, with the OR being 1.43 (95% CI, 1.04-1.95) and 2.40 (95% CI, 1.61-3.59), respectively. In addition, a significant difference in the distribution of haplotype frequencies between cases and controls was observed.</p><p><b>CONCLUSION</b>Functional polymorphism in MTHFR is associated with increased risk of lung cancer in Chinese population.</p>

A case-control study on the polymorphisms of methylenetetrahydrofolate reductases, drinking interaction and susceptibility in colorectal cancer / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between methylenetetrahydrofolate reductases (MTHFR) polymorphisms and colorectal cancer susceptibility.</p><p><b>METHODS</b>A case-control study of 126 patients and 343 healthy controls was conducted to investigate the roles of MTHFR C677T and A1298C polymorphisms in colorectal cancer development. Genotypes of C677T and A1298C polymorphisms were analyzed by polymerase chain resction-restriction fragment length polymorphism (PCR-RFLP) methods.</p><p><b>RESULTS</b>The frequencies of MTHFR 677T and 1298C allele were 39.7% and 17.1%, respectively. After adjustment for age and sex, the MTHFR 1298C alleles seemed to have reduced association on the risk of colorectal cancer comparing to wild types. Among those with 677T and 1298A alleles, a decreased risk of colorectal cancer was observed: a 4-fold decrease in colorectal cancer risk (OR = 0.552, 95% CI: 0.265 - 1.150) in those with 677T and 1298C alleles. Men who were ex-drinkers and with MTHFR 1298C allele had a 2-fold increase in risk of colorectal cancer (OR = 3.307, 95% CI: 0.521 - 17.698) while no increased risk was seen among those current-drinkers.</p><p><b>CONCLUSIONS</b>This study suggested that certain MTHFR C677T and A1298C might be associated with the risk of colorectal cancer development. The interaction between MTHFR 1298AC polymorphisms and ex-drinking might also serve as a risk factor of colorectal cancer.</p>

Association between genetic polymorphisms in methylenetetrahydrofolate reductase and risk of breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the association between genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and risk of breast cancer among women.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>These findings suggest that 677CT polymorphism in MTHFR may be a genetic susceptibility factor for breast cancer among Chinese women.</p>

Relation between single nucleotide polymorphism in estrogen-metabolizing genes COMT, CYP17 and breast cancer risk among Chinese women / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To test the hypothesis whether polymorphism in estrogen-metabolizing genes, COMT and CYP17, impacts on the risk of breast cancer among Chinese women.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>The allele encoding for low activity COMT, but not CYP17, may be a genetic risk factor for breast cancer among Chinese women.</p>

Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>