GSTP1, ERCC1 and ERCC2 Polymorphisms,Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whethersingle nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predictthe overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods:SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessedusing TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up periodwas 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showedGSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G(HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer,with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1,GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-basedchemotherapy for colorectal cancer patients.     

Influences of ERCC1, ERCC2, XRCC1, GSTP1, GSTT1, and MTHFR polymorphisms on clinical outcomes in gastric cancer patients treated with EOF chemotherapy

Tumor Biology - This study investigated the associations between genetic polymorphisms of six genes involved in DNA repair, detoxification pathways, and fluoropyrimidine metabolism and clinical...     

Genetic polymorphisms of CYP2E1, GSTT1, GSTP1, GSTM1, ALDH2, and ODC and the risk of advanced precancerous gastric lesions in a Chinese population.

There have been few studies of the associations of genetic polymorphisms with precancerous gastric lesions. We conducted a cross-sectional study to compare the prevalences of several genetic polymorphisms in 302 subjects with mild chronic atrophic gastritis with prevalences in 606 subjects with deep intestinal metaplasia or dysplasia. This stratified random sample of 908 subjects was selected and analyzed for genetic polymorphisms from 2,628 individuals who had gastric biopsies with histopathology in 1989 in Linqu County, Shandong Province, China. In subjects with mild chronic atrophic gastritis, the frequencies of the variant (less common) alleles of CYP2E1 RsaI, CYP2E1 DraI, GSTP1, ALDH2, and ODC were, respectively, 0.156, 0.201, 0.189, 0.190, and 0.428. The frequencies of the null genotypes of GSTM1 and GSTT1 in the mild chronic atrophic gastritis group were 0.509 and 0.565, respectively. Comparing mild chronic atrophic gastritis with deep intestinal metaplasia or any degree of dysplasia, we found no statistically significant associations with any genotype from these loci for dominant, additive, or recessive inheritance models. There was no statistically significant evidence of multiplicative interactions between any pair of genotypes based on CYP2E1 RsaI, CYP2E1 DraI, GSTP1, GSTM1, or GSTT1; nor between Helicobacter pylori status and any of these five loci; nor between smoking status and GSTP1, GSTM1, or GSTT1; nor between alcohol consumption and ALDH2. Statistically significant interactions were noted between salt consumption and GSTP1 and between sour pancake consumption and CYP2E1 RsaI. There was, moreover, a statistically significant interaction (odds ratio, 1.78; 95% confidence interval, 1.03-3.08) between CYP2E1 DraI and smoking at least one cigarette per day. A positive but not statistically significant interaction was also seen between CYP2E1 RsaI and smoking status. These polymorphisms do not seem to govern progression from mild chronic atrophic gastritis to advanced precancerous gastric lesions, but the effects of smoking may be accentuated in individuals carrying variants of CYP2E1.     

GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population

Objectives: In a population-based case–control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene–gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. Methods: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. Results: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1–11.2) for gastric cancer and 0.9 (95% CI: 0.2–4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. Conclusion: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.     

Genetic polymorphisms in XRCC1 gene and susceptibility to glioma in Chinese Han population

Glioma is the most common type of primary brain malignancy in adults. The X-ray repair cross-complementing group 1 (XRCC1) is an important candidate gene for influencing the pathogenesis of glioma. This study aimed to evaluate the potential association between XRCC1 genetic polymorphisms and glioma susceptibility. This case–control study was conducted in Chinese Han populations consisting of 620 glioma cases and 630 cancer-free controls. XRCC1 genetic polymorphisms were detected by the polymerase chain reaction–restriction fragment length polymorphism and verified using DNA sequencing methods. The c.910A>G and c.1779C>G genetic polymorphisms were identified in this study. Our data suggested that the genotypes/alleles of these two genetic polymorphisms were statistically associated with the increased risk of glioma. As for c.910A>G, the risk of glioma for genotype GG was significantly higher than wild genotype AA (odds ratio (OR) = 1.98, 95 % confidence interval (CI) 1.33–2.94, P = 0.001). As for c.1779C>G, the genotype GG was statistically associated with the increased risk of glioma compared to wild genotype CC (OR = 1.80, 95 % CI 1.17–2.78, P = 0.007). Both of alleles G in c.910A>G and c.1779C>G may contribute to glioma susceptibility (G versus (vs.) A, OR = 1.30, 95 % CI 1.09–1.54, P?=?0.003; G vs. C, OR = 1.19, 95 % CI 1.00–1.42, P = 0.045). Our findings indicate that the c.910A>G and c.1779C>G genetic polymorphisms are associated with the susceptibility to glioma in Chinese Han populations and might be used as molecular markers for evaluating glioma risk.     

Genetic Polymorphisms of CYP2E1 and GSTP1 in a South Indian Population - Comparison with North Indians,Caucasians and Chinese

CYP2E1 and GSTP1 enzymes belong to phase I and phase II group of drug metabolizing enzymes respectively ‍which are involved in the metabolic activation and detoxification of various potential genotoxic compounds. The ‍functional polymorphism in these genes exhibit inter-individual variations in susceptibility towards various diseases ‍and difference in therapeutic response. The variant sequences of these genes differ considerably between ethnic ‍groups. Therefore, the objective of the study was to assess the prevalence of CYP2E1 & GSTP1 gene variants in ‍healthy volunteers of Tamilnadu, a population of South India. The genotype distribution of CYP2E1*1B A2A2, A2A1 ‍and A1A1 were 61%, 36% and 3% respectively. The distribution of CYP2E1*5B c1c1, c1c2 genotypes were 99.2%and ‍0.8%. CYP2E1*6 DD, DC and CC genotype frequencies were 72%, 25% and 3% respectively. The allele frequencies ‍of CYP2E1*1B, CYP2E1*5B and CYP2E1*6 were A2- 0.79 A1- 0.21, c1-0.996 c2 - 0.004 and D- 0.84 C- 0.16 respectively. ‍The genotypic distribution of GSTP1 (Ile/Val) were Ile/Ile - 44%, Ile/Val -47% and Val/Val- 9 % whereas, the allelic ‍frequencies were 0.67 for Ile and 0.33 for Val allele. The molecular studies in these enzymes provide basis for further ‍epidemiological investigations in the population where the functional mutations in the genes alter therapeutic response ‍and acts as susceptibility markers for various clinical conditions.     

Genetic polymorphisms in centrobin and Nek2 are associated with breast cancer susceptibility in a Chinese Han population

Centrosome aberrations have been suggested to cause chromosomal instability and aneuploidy, and eventually promote cancer development. The Centrobin and Nek2 proteins interact with each other and both are involved in centrosome duplication and chromosome segregation. This study aimed to investigate whether genetic polymorphisms in these two genes may affect breast cancer susceptibility in Chinese Han population using a haplotype-based analysis. Five single nucleotide polymorphisms (SNPs) in centrobin and four SNPs in Nek2 were genotyped in 1,215 cases of infiltrating ductal breast cancer and 1,215 age-matched cancer-free controls from Chinese Han population. The results showed that CATCG haplotype of centrobin was strongly associated with decreased breast cancer risk (adjusted OR = 0.14, 95 % CI = 0.09–0.22), which was mainly driven by the C allele of SNP rs11650083 (A>C, located in exon 12, resulting in Pro578Gln). None of the individual SNPs in Nek2 was associated with breast cancer risk. However, haplotype GTAT of Nek2 was associated with increased risk of breast cancer (adjusted OR = 1.56, 95 % CI = 1.18–2.06) and its risk was significantly elevated among women with both family history of cancer and a longer menarche-first full-term pregnancy (FFTP) interval (>11 years) (adjusted OR = 5.31, 95 % CI = 1.97–14.32). Furthermore, women harboring both at-risk haplotype GTAT of Nek2 and protective haplotype CATCG of centrobin were linked with decreased breast cancer risk, suggesting that the association between genetic variants of Nek2 and increased breast cancer risk was modified by genetic variants of centrobin. Our results indicate that genetic polymorphisms of centrobin and Nek2 are related to breast cancer susceptibility in Chinese Han women.     

ERCC1, XRCC1, and GSTP1 Polymorphisms and Treatment Outcomes of Advanced Epithelial Ovarian Cancer Patients Treated with Platinum-based Chemotherapy

Objective: The first line regimen for treating epithelial ovarian cancer (EOC) is platinum-based chemotherapy. Various factors impact its effectiveness including polymorphisms of enzymes in platinum-related metabolism processes.  Methods: We conducted the study to investigate the association between polymorphisms of ERCC1, XRCC1 and GSTP1, which responsible for platinum’s metabolisms in Thai epithelial ovarian cancer patients. Results: Fifty-two patients with advanced epithelial ovarian cancer were enrolled into this study. Genotyping analysis of ERCC1 (C->A, rs3212986), XRCC1 (A->G, rs25487) and GSTP (A->G, rs1695) were performed which variant allele frequencies were found at 35.6%, 28.9% and 10.6%, respectively. Patients with homozygous variant type (A/A) of ERCC1 C8092A had higher rate of platinum-resistance (75% vs 16.7%, p =0.046). In addition, the significant association of GSTP1 polymorphism and grade 2 anemia was found. Patients with A/G genotype of GSTP1 had higher rate of grade 2 anemia (81.8% vs 46.3%, p =0.036). Conclusions: Genetic polymorphisms of ERCC1, and GSTP1 might be useful biomarkers for prediction of clinical benefit and toxicities of platinum-based chemotherapy in Thai epithelial ovarian cancer patients.     

Genetic association of PLCE1, C11orf92-C11orf93, and NOC3L with colorectal cancer risk in the Han population

Colorectal cancer (CRC) is a common malignant tumor that is influenced by an interaction between genetic and environmental factors. Currently, the inherited factors of CRC are unclear. Our study selected 19 tag single nucleotide polymorphisms (tSNPs) to investigate whether they were associated with CRC in the Han population. In this Han Chinese case–control study, we genotyped 203 CRC cases and 296 controls using Sequenom MassARRAY technology and analyzed their associations with CRC using χ² tests, SNPStats software, and SHEsis software. Based on χ² tests, PLCE1 -rs2077218, rs11187877 (p?=?0.049) and C11orf92-C11orf93-rs3802842 (p?=?0.023) correlate with CRC risk. In the genetic model analyses, we found the genotype “CC” of rs3802842 in C11orf92-C11orf93 may significantly increase CRC risk in the recessive model (p?=?0.0071), whereas “GT” of rs17109928 in NOC3L may decrease the risk in the over-dominant model (p?=?0.0091). Using SHEsis software, we found PLCE1 and NOC3L are strongly linked, and the “GCCATTCTGTC” haplotype may increase the risk of CRC (p?=?0.049). We found three genes (PLCE1, C11orf92-C11orf93, and NOC3L) are associated with CRC susceptibility. In combination with previous reports, our results suggest that these genes may be associated with CRC in the Han population.     

ERCC2, ERCC1 polymorphisms and haplotypes,cooking oil fume and lung adenocarcinoma risk in Chinese non-smoking females

Background

Excision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence the risk of lung cancer. This study aimed to investigate the association between the ERCC2 751, 312 and ERCC1 118 polymorphisms and the risk of lung adenocarcinoma in Chinese non-smoking females.

Methods

A hospital-based case-control study of 285 patients and 285 matched controls was conducted. Information concerning demographic and risk factors was obtained for each case and control by a trained interviewer. After informed consent was obtained, each person donated 10 ml blood for biomarker testing. Three polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

This study showed that the individuals with the combined ERCC2 751AC/CC genotypes were at an increased risk for lung adenocarcinoma compared with those carrying the AA genotype [adjusted odds ratios (OR) 1.64, 95% confidence interval (CI) 1.06-2.52]. The stratified analysis suggested that increased risk associated with ERCC2 751 variant genotypes (AC/CC) was more pronounced in individuals without exposure to cooking oil fume (OR 1.98, 95%CI 1.18-3.32) and those without exposure to fuel smoke (OR 2.47, 95%CI 1.46-4.18). Haplotype analysis showed that the A-G-T and C-G-C haplotypes were associated with increased risk of lung adenocarcinoma among non-smoking females (ORs were 1.43 and 2.28, 95%CIs were 1.07-1.91 and 1.34-3.89, respectively).

Conclusion

ERCC2 751 polymorphism may be a genetic risk modifier for lung adenocarcinoma in non-smoking females in China.     

Effect of DPYD,MTHFR, ABCB1, XRCC1, ERCC1 and GSTP1 on chemotherapy related toxicity in colorectal carcinoma

ABCB1, DPYD, MHTFR, XRCC1, ERCC1, GSTP1 and UGT1A1 genetic variants affect proteins related to CRC chemotherapy toxicity.A retrospective cohort study was conducted in 194 CRC patients.In first line treatment, DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 4.85; p = 0.03); GSTP1 G-allele (OR = 3.01; p = 0.005) and MTHFR rs1801133 T allele (OR = 2.51; p = 0.03) with respiratory toxicity; GSTP1 G-allele with cardiovascular toxicity (OR = 4.05; p = 0.01); ERCC1 rs11615 GG genotype with neurological toxicity (OR = 3.98; p = 0.01) and with asthenia (OR = 2.91; p = 0.08); XRCC1 rs1799782 T allele (OR = 0.31; p = 0.03) and GSTP1 G-allele (OR = 1.81; p = 0.01) with cutaneous toxicity. In second line treatment, XRCC1 rs1799782 T-allele was associated with asthenia (OR = 0.17; p = 0.03) and XRCC1 rs25487 T-allele with gastrointestinal toxicity (OR = 3.03; p = 0.005). After stratifying by treatment, in the 5-Fluorouracil group, the DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 2.76; p = 0.003), ABCB1 rs1045642 T-allele with the need of treatment adjustment due to toxicity (OR = 3.06; p = 0.01), and rs1045642 CC genotype with gastrointestinal toxicity (OR = 5.80; p = 0.03). In the capecitabine group, the MTHFR rs1801131 CC genotype was associated with asthenia (OR = 3.48; p = 0.009). In the oxaliplatin group, rs1045642 TT genotype was associated with the need to adjust treatment (OR = 0.32; p = 0.02), ERCC1 rs11615 GG genotype with asthenia (OR = 3.01; p = 0.01) and rs1615 GSTP1 GG genotype with respiratory toxicity (OR = 5.07; p = 0.009).ABCB1 rs1045642 T-allele reduces the need for treatment modification with both 5FU and oxaliplatin. Although several biomarkers predicted different toxic effects, they cannot be considered as risk factors for severe toxicity.     

Genetic polymorphisms in ATM,ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China

Polymorphisms in DNA repair and apoptosis genes are suspected to alter the individual susceptibility to develop lung cancer. We investigated the relationship between polymorphisms in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu) and iASPP (A67T) and the risk of developing lung cancer. A case–control study was conducted with 315 patients with lung cancer and 315 cancer-free controls, matched on age and sex. Genotypes were detected using the ABI 7500 real-time PCR system. The T/T homozygote in ERCC1 (Asn118Asn) was correlated with a strong statistically significant increased risk of developing lung cancer (adjusted OR = 2.44; 95% CI = 1.13–5.28; P = 0.023), especially lung adenocarcinoma (adjusted OR = 3.18) and small cell lung cancer (adjusted OR = 6.08). For iASPP (A67T), smokers with at least one T allele (A/T + T/T) were more likely to develop lung cancer (95% CI, 1.07–2.84, P = 0.026). Subjects carrying the G allele in APE1 (Asn148Glu) had a decreased risk of lung cancer (P < 0.05), which showing a protective effect. Our results suggest that polymorphism Asn118Asn in ERCC1, A67T in iASPP and Asn148Glu in APE1 may associated with early onset of lung cancer as well as some specific subtype of lung cancer. Detection of these biomarkers may be helpful for screening this high-risk population for primary preventing.     

Association of single-nucleotide polymorphisms in ERCC1 and ERCC2 with glioma risk

We conducted a case–control study to assess the role of three single-nucleotide polymorphisms (SNPs) in excision repair cross-complementation group 1 (ERCC1) and two SNPs in excision repair cross-complementation group 2 (ERCC2) on the glioma risk in a Chinese population, and investigate the gene–environmental interaction for the cancer risk. A 1:2 matched case–control study was conducted. Logistic regression analysis revealed that individuals carrying ERCC1 rs2298881 CC genotype were associated with risk of glioma when compared with AA genotype carriers. The significant associations of ERCC1 rs2298881 polymorphism with glioma susceptibility were observed in both the dominant and the recessive models. In a stratification analysis, we found that ERCC1 rs2298881 variants showed an increased association with the risk of glioma in males, ever smokers, and high-grade glioma cases. In conclusion, our study suggests that ERCC1 rs2298881 polymorphism is associated with risk of glioma in codominant, dominant, and recessive models, especially in males, smokers, and high-grade glioma cases. This finding could be useful in revealing the genetic characteristics of glioma and suggests more effective strategies for prevention and treatment.     

ERCC1和Pim-1表达与非小细胞肺癌化疗疗效的相关性

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者肺癌组织标本中ERCC1和Pim-1的表达与临床特征及化疗疗效的相关性。方法:对我院病理确诊的70例NSCLC患者肿瘤组织,通过实时定量荧光PCR法检测ERCC1和Pim-1基因mRNA表达水平,回顾性分析ERCC1和Pim-1基因表达与临床病理关系、铂类化疗疗效和总生存情况。结果:70例NSCLC患者肿瘤组织中ERCC1和Pim-1高表达患者比率分别为37.14%（26/70）和61.43%（43/70）,ERCC1高表达与性别、吸烟史、组织类型、TNM 分期均无关（P＞0.05）,Pim-1高表达与性别、吸烟史相关（P＜0.05）,而与组织类型、TNM分期无关（P＞0.05）。ERCC1和Pim-1共同高表达率为20.00%（14/70）。ERCC1高表达组患者化疗有效率（19.23%,5/26）显著低于低表达组患者（47.73%,21/44）(P＜0.05)。Pim-1高表达组患者化疗有效率（34.88%,15/43）和低表达组患者（40.74%, 11/27）无统计学差异(P＞0.05)。ERCC1和 Pim-1高表达组的中位生存期（median survival time,MST）为27个月和24个月低于低表达组的33个月和 27个月,但无统计学差异（P＞0.05）。结论:NSCLC患者中ERCC1低表达组患者化疗有效率和存活率高,是化疗受益的指标。     

No association between the USP7 gene polymorphisms and colorectal cancer in the Chinese Han population

Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population.     

Lack of association of NQO1 and GSTP1 polymorphisms with multiple myeloma risk

Individual differences in xenobiotica metabolising capacity can influence susceptibility to multiple myeloma. NQO1 and GSTT1 polymorphisms were recently reported as risk factors for multiple myeloma and GSTP1 genotype was found to be a prognostic marker for therapy outcome in multiple myeloma. The aim of this study was to determine whether specific defective alleles of NQO1 (P187S) and GSTP1 (I105V) genes are associated with increased risk of multiple myeloma. Individual genotypes of 128 patients affected by multiple myeloma and 245 healthy controls were determined and our results do not support any major role of NQO1 or GSTP1 polymorphisms in multiple myeloma pathogenesis.     

中国汉族人群中BRCA1和BRCA2基因突变携带者患乳腺癌风险的研究

背景与目的：BRCA1和BRCA2基因突变携带者终生患乳腺癌和卵巢癌的风险显著增高。通过遗传咨询,突变携带者可采取适当的措施来降低相应肿瘤的发生风险。目前,相关的报道几乎均为白种人,尚缺乏中国人群的资料。该研究旨在探索中国汉族人群中BRCA1和BRCA2基因突变携带者患乳腺癌的风险。方法：回顾20个经基因检测证实携带BRCA1或BRCA2致病性基因突变的汉族乳腺癌高风险家系。利用Kaplan-Meier生存分析法对女性BRCA1/2基因突变携带者单侧乳腺癌及对侧乳腺癌的累积发病风险进行估算。结果：BRCA1和BRCA2基因突变携带者70岁时单侧乳腺癌的累积发病风险(外显率)分别为67.2%(sx 0.100)和76.8%(sx 0.079)。与BRCA1不同的是,BRCA2基因突变携带者70岁后乳腺癌累积发病率继续增加,到80岁时达93.1%。BRCA1/2基因突变携带者对侧乳腺癌10年和20年的累积发病率分别为19.4%(sx 0.089)和50.3%(sx 0.155)。结论：中国汉族人群中BRCA1和BRCA2基因突变携带者具有很高的乳腺癌发病风险。因而对中国高风险人群进行BRCA1/2基因突变检测具有重要临床意义。     

中国汉族人群前列腺癌易感性与TLR4基因单核苷酸多态性的研究

目的 探讨Asp299Gly(rs4986790)、Thr399Ile(rs4986791)、rs11536889单核苷酸多态性(SNP)与前列腺癌(PCa)易感性和严重程度的关系.方法 采用病例对照研究方法,选取组织学证据确诊的PCa患者96例为PCa组,良性前列腺增生(BPH)患者87例为BPH组,健康者92例为健康对照组.记录研究对象的临床资料并计算Gleason评分,PCR-RFLP法分析各组的基因型.结果 PCa组、BPH组及健康对照组的年龄、前列腺癌家族史所占比例、前列腺特异抗原(PSA)水平比较,差异均有统计学意义(P=0.000);PCa组、BPH组及健康对照组的Asp299Gly和Thr399Ile基因型频率分布比较,差异无统计学意义(P﹥0.05),但3组间rs11536889基因型频率分布比较,差异有统计学意义[PCa组/(BPH组+健康对照组),CC/GC vs GG,OR=2.152,95%CI:1.280~3.618,P﹤0.05];Gleason评分≥7分组GC+CC分布比例高于Gleason评分﹤7分组(OR=2.378,95%CI:1.042~4.427,P﹤0.05).结论 TLR4基因rs11536889 SNP可能与PCa发病和病情严重程度相关.     

中国汉族人群吸烟行为相关基因及其与肺癌相关研究进展

全基因组关联研究（genome-wide association study,GWAS）设计基于较大病例对照研究样本量,并要求后期以多个独立研究验证和筛选前期结果。吸烟行为相关GWAS已在多个种族人群中进行,但以欧美人群居多,鉴于不同种族人群间存在遗传易感性差异,本文就近年在中国汉族人群中进行的吸烟行为相关基因GWAS或在该人群进行既往位点验证和筛选的研究及其与肺癌的相关研究进展作一综述。