Most chemical carcinogens are metabolized and activated in vivo by phase I enzymes including the microsomal cytochromes P450 and epoxide hydroxylases. The carcinogens and their metabolites are detoxified by phase II enzymes that include various transferases such as glutathion-S-transferases (GST). Increasing numbers of studies have demonstrated the association of the polymorphisms in GSTM1 (a member of GST) and CYP1A1 genes with the susceptibility to lung cancer. Subsequently, the polymorphisms appear to be important biomarkers that provide information for assessment of exposure and total burden of environmental carcinogens. Therefore, the investigation of the polymorphisms in these genes will provide information not only for the prediction of individual cancer risk but also for the prevention of cancer. In this review, we will summarize the polymorphisms in the GSTM1 and CYP1A1 genes and their relation to lung cancer susceptibility.
Malignant neoplasm of lung ; seconds ; CYP1A1 gene ; GST Gene ; Cytochrome P-450 CYP1A1

OBJECTIVETo investigate the association between CYP1A1 gene polymorphisms and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families through family-based association study.

METHODSA total of 457 Cantonese nuclear families,consisting of 2134 members, were recruited as subjects. Each family included two parents and at least one offspring with nasopharyngeal carcinoma. Two single nucleotide polymorphisms (SNP) in CYP1A1 named m1 (rs4646903) and m2 (rs1048943), were genotyped by PCR-RFLP assay and verified by directly sequencing. The genotype data were analyzed with family-based association test (FBAT) software to check the linkage and association between the two genetic markers and susceptibility of nasopharyngeal carcinoma.

RESULTSFBAT analysis showed that the minor allele frequencies (MAF) of the two SNP were 0.442 (C) and 0.339 (G) respectively. For m1 polymorphism in CYP1A1 gene was not significantly associated with nasopharyngeal carcinoma in our study population whether stratified with VCA-IgA or not (without stratification: chi2 = 2.399, P = 0.301; with stratification: low-titer group (VCA-IgA <1:80), MAF = 0.457 (C), chi2 = 1.221, P = 0.543; high-titer group (VCA-IgA > or = 1:80), MAF = 0.427 (C), chi2 =2.832, P = 0.243) . For m2 polymorphism, when VCA-IgA <1:80, the G allele showed decreased transmission under additive and dominant model (MAF = 0.347 (G); Zadditive = -2.120, Padditive = 0.034; Zdominant = - 2.303, Pdominant = 0.021) and a boundary P value was got with global statistic (chi2 = 5.394, P = 0.067) . Haplotype TG (0.057), constructed by m1 and m2, might decrease nasopharyngeal carcinoma risk (Z= -2.002, P=0.045). A boundary P value was also got with global statistic (chi2 =7.067, P=0.070).

CONCLUSIONThere was no statistical significance between m1 polymorphism and susceptibility of nasopharyngeal carcinoma in Cantonese nuclear families. And this study showed that m2 polymorphism might associated with the decrease of nasopharyngeal carcinoma in Cantonese nuclear families.

Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Nasopharyngeal Neoplasms ; genetics ; Polymorphism, Single Nucleotide

OBJECTIVETo find out the distributive features of some metabolic genes polymorphisms in Han population of south area of China.

METHODSStudy population was obtained from the controls of a community based case-control study, which included 290 blood relatives (inner control) and 404 non-blood relatives (outer control).

RESULTSFrequencies of CYP1A1, GSTM1 and GSTT1 polymorphisms had no significant difference among confounding factors, such as sex, living areas, stomach cancer family history and history of tobacco smoking etc. Some controls showed significant difference in age group and alcohol drinking which would be adjusted in analysis of the relationship between polymorphisms and cancers. CYP1A1 Ile/Val and Val/Val genotypes were 33.43% and 5.62% respectively, which were similar to other results from Chinese and Japanese, but higher than those from Caucasians in American, Europe and African-Americans. GSTM1 null allele frequency was 53.48% in our population, which showed difference even among Chinese in different areas. GSTT1 null allele frequency was 45.78%, which was significantly higher than that in Caucasians and African-American.

CONCLUSIONThe frequencies of CYP1A1 Ile/Val, Val/Val and GSTT1 null in Han population in south area of China are significantly higher than those in other races, while the ethnic difference of frequency of GSTM1 null is less.

China ; Cytochrome P-450 CYP1A1 ; genetics ; DNA ; genetics ; Female ; Gene Frequency ; Genotype ; Geography ; Glutathione Transferase ; genetics ; Humans ; Male ; Polymorphism, Genetic

PURPOSE: The incidence of nonphysiologic neonatal hyperbilirubinemia is twice as high in East Asians as in whites. Recently, UGT1A1 mutation was found to be a risk factor for neonatal hyperbilirubinemia. In congenitally-jaundiced Gunn rats, which lack expression of UDP-glucuronosyltransferase, alternative pathways can be stimulated by inducers of CYP1A1 and CYP1A2 enzymes. CYP1A2 plays a major role in bilirubin degradation of the alternate pathway. We studied the relationship between UGT1A1 and CYP1A2 gene polymorphism of neonatal hyperbilirubinemia in Koreans. METHODS: Seventy-nine Korean full term neonates who had hyperbilirubinemia(serum bilirubin >12 mg/dL) without obvious causes of jaundice, were analyzed for UGT1A1 and CYP1A2 gene polymorphism; the control group was sixty-eight. We detected the polymorphism of Gly71Arg of UGT1A1 gene by direct sequencing and T2698G of CYP1A2 by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) using MboII and direct sequencing. RESULTS: Allele frequency of Gly71Arg mutation in the hyperbilirubinemia group was 32 percent, which was significantly higher than 11 percent in the control group(P<0.0001). Mutant gene frequency of T2698G was 41.8 percent in patients and 32.3 percent in the control group(P=0.015), but allele frequency was 21 percent in patients and 19 percent in the control group, which was not significantly higher(P=0.706). There was no relationship between mutations of two genes(P=0.635). CONCLUSION: The polymorphism of UGT1A1 gene(Gly71Arg) and CYP1A2 gene(T2698G) was detected in Korean neonatal hyperbilirubinemia. Only polymorphisms of Gly71Arg in UGT1A1 were significantly higher than control group.
Asian Continental Ancestry Group ; Bilirubin ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP1A2* ; Gene Frequency ; Humans ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal* ; Incidence ; Infant, Newborn* ; Jaundice ; Rats, Gunn ; Risk Factors

OBJECTIVETo investigate the association of MspI polymorphism of Cytochrome P4501A1 (CYP1A1) gene and smoking to the susceptibility to coronary artery disease (CAD).

METHODSThe genotypes of CYP1A1 MspI site were detected using the methods of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 349 cases with CAD and 404 non-CAD as controls. CAD diagnosis was confirmed by coronary angiograms. Genetic risk of CYP1A1 genotypes was analyzed by smoking index (SI).

RESULTSThe frequency of the predominant homozygotes TT, heterozygotes TC and the rare homozygotes CC in CAD group were not different with that of the controls (chi(2) = 3.224, P = 0.200). But in the smokers, the frequency of CC in CAD group was higher than that of non-CAD group (P = 0.002), while its odds ratio was 3.142 [95% confidence interval (CI) 1.481 - 6.668]. The odds ratio of genotype CC and heterozygote TC was 2.215 (95% CI 1.087 - 4.510) in the low dose cigarette smoking group, and was 1.407 (95% CI 0.709 - 2.791) in the high dose cigarette smoking group.

CONCLUSIONBoth MspI polymorphism of CYP1A1 gene and smoking exposure promote the development of CAD.

Aged ; Coronary Artery Disease ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Smoking ; genetics

BACKGROUNDVariation in prostate cancer incidence between different racial groups has been well documented, for which genetic polymorphisms are hypothesized to be an explanation. We evaluated the association between polymorphisms in the cytochrome P-450 CYP1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes and genetic susceptibility to prostate cancer in Chinese men.

METHODSTwo hundred and eight prostate cancer patients and 230 age matched controls were enrolled in this study. All DNA samples from peripheral blood lymphocytes were genotyped for common genetic polymorphisms of the CYP1A1 and GSTM1 genes using the oligonucleotide microarray (DNA chip) technique and the polymorphism results confirmed by sequencing. The different polymorphisms in prostate cancer patients were also analyzed according to age at diagnosis, prostate specific antigen level, cancer stage and grade (Gleason score).

RESULTSThe prevalence of the GSTM1 (0/0) genotype was significantly higher in prostate cancer patients (58.2%) than in controls (41.7%, P<0.05). Further analysis demonstrated that the prostate cancer patients with a GSTM1 (0/0) genotype were younger than those with the GSTM1 (+/+) genotype (P=0.024). No significant differences in the frequency distributions of CYP1A1 polymorphisms were observed between prostate cancer patients and controls.

CONCLUSIONGSTM1 (0/0) gene polymorphism may be linked to prostate cancer risk and early age of onset in Chinese.

Aged ; Aged, 80 and over ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Glutathione Transferase ; genetics ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Prostatic Neoplasms ; genetics

OBJECTIVETo study the relationship between CYP1A1 genetic polymorphism and intrahepatic cholestasis of pregnancy (ICP) in Chengdu of China.

METHODSMspI and Ile/Val genotypes of CYP1A1 gene were detected with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification-PCR (ASA-PCR) in a case-control study, including 100 cases of ICP and 100 controls.

RESULTSThere was no significant correlation between MspI polymorphism and ICP susceptibility (P>0.05). However, the Ile/Val+Val/Val genotypes of CYP1A1 significantly increased the risk of ICP (P=0.047, OR=1.768).

CONCLUSIONThe Ile/Val polymorphism in exon 7 of CYP1A1 may be associated with the susceptibility of ICP in Chengdu. The MspI polymorphism of CYP1A1 is not associated with the risk of ICP in Chengdu.

Case-Control Studies ; Cholestasis, Intrahepatic ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications ; genetics

OBJECTIVETo determine the correlation of the CYP1A1 (rs4646422) gene polymorphisms with male infertility in the Chinese Han population.

METHODSUsing the Mass ARRAY iPLEX GOLD technique, we conducted a case-control study on theCYPlA1 (rs4646422) gene polymorphisms in 636 infertile males aged 21-49 years (case group) and 442 normal healthy men aged 23-47 years (control group) of the Chinese Han population. We analyzed the genotypes and allele frequencies in the two groups ofsubjects with the SPSS 20.0 software.

RESULTSCompared with the wild homozygous genotype GG, the heterozygous genotype AG (OR = 1.06, 95% CI 0.81-1.38) and homozygous genotype AA (OR = 1.11, 95% CI 0.56-2.21) showed no correlation with male infertility, nor did the mutant allele A (OR = 1.06, 95% CI 0.85-1.32) in comparison with the wild allele G.

CONCLUSIONThe CYP1A1 (rs4646422) gene polymorphisms might not be correlated with male infertility in the Chinese Han population.

Adult ; Alleles ; Case-Control Studies ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genotype ; Homozygote ; Humans ; Infertility, Male ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Young Adult

OBJECTIVETo investigate the association between CYP1A1, GSTM1, T1, UGT1A7 polymorphisms and colorectal cancer risk.

METHODSA case-control study of 140 patients with cancers and 343 health controls was conducted to investigate the role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case-control study and case-only study. Genotypes of four genes polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.

RESULTSThe CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254-0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no significant association with the increased risk of colorectal cancer while the mutant variants of UGT1A7 might increase the risk of colorectal cancer significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015-6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7.

CONCLUSIONThis study suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of colorectal cancer.

Cohort Studies ; Colorectal Neoplasms ; genetics ; Cytochrome P-450 CYP1A1 ; genetics ; Follow-Up Studies ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Logistic Models ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVEBased on the distribution of genetic polymorphisms regarding phase I metabolic enzyme cytochrome P450 1A1 (CYP1A1) and phase II metabolic enzymes glutathione S-transferase GSTM1 and GSTT1 genotypes in acute leukemia patients and health controls among general population of Hunan in China, this study was to explore the relationship between these gene polymorphisms and the susceptibility to acute leukemia.

METHODSUsing case-control methodology, we studied 204 healthy controls and 232 patients with acute leukemia, of which 112 patients were suffering acute lymphoblastic leukemia (ALL) and 120 with acute non-lymphoblastic leukemia (ANLL). The frequencies of the genotypes were detected by PCR and PCR-RFLP techniques.

RESULTSThe variation frequencies of CYP1A1 gene (Msp I polymorphisms, site 3801T-C variation) in ALL and ANLL groups were 74.1% and 70.8% respectively which were higher than 63.3% appeared in the healthy controls. However, the differences between patients (ALL or ANLL) and healthy controls were not statistically significant (P > 0.05 for both). The null genotype of GSTM1 (GSTM1 -/-) in ALL group was 60.7%, which was not significantly different from the controls (55.4%). However, GSTM1 -/- genotype in ANLL group was 68.3%, significantly different from the controls (P < 0.05). The null genotypes among GSTT1 (GSTT1 -/-) in ALL, ANLL and control group were 50.9%, 55.0% and 49.0% but their differences were not statistically significant (P > 0.05). The incidences of GSTM1 -/- and GSTT1 -/- combined genotype in ALL, ANLL and control group were 33.0%, 40.0% and 27.5%, of which the difference between ANLL group and control group was statistically significant (P < 0.05) and CYP1A1 gene heterozygous mutation type or homozygous mutation type combined with GSTM1 -/- and GSTT1 -/- increased the risk of ANLL (OR value 1.890, 95% CI: 1.084-3.295).

CONCLUSIONThese results indicated that both the variation of CYP1A1 gene or GSTT1 -/- genotype alone might not be associated with the susceptibility of acute leukemia while GSTM1 -/- genotype alone or combined with GSTT1 -/- or the 3801 T-C variation of CYP1A1 gene were correlated with ANLL. These findings suggest that GSTM1 - / - genotype alone or in combination with other defective genotypes might serve as risk factors to the etiology of ANLL.

Case-Control Studies ; China ; Cytochrome P-450 CYP1A1 ; genetics ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Glutathione Transferase ; genetics ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Risk Factors