[Study on the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) and susceptibility to breast cancer in Chinese women].

OBJECTIVE: To investigate the relationship between polymorphisms of genes (CYP17, CYP19 and SULT1A1) involved in estrogen metabolism and susceptibility to breast cancer in Chinese women. METHODS: A case-control study was performed. PCR-base restriction fragment length polymorphism (PCR-RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the polymorphism distribution of CYP17, CYP19 and SULT1A1 in 213 breast cancer cases and 430 matched controls. Logistic regression analyses were used to determine the OR, multivariate adjusted OR and 95% CI of each and all three genes and estrogen exposure factors on the risk of breast cancer. Relationship between polymorphisms and clinic-pathological features was also assessed. RESULTS: The frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P > 0.05). The frequency His allele of SULT1A1 in cases (13.6%) was significant higher than that of controls (9.5%) (P = 0.03). There was also significant difference in the frequencies of (TTTA)10 allele CYP19 which was 12.4% in cases and 8.2% in controls (P = 0.02). Multigenic model indicated that there was an increased risk of breast cancer with more numbers of high-risk genotypes in a dose-response effect (trend P = 0.05). Data from multivariate analysis showed that the allele of SULT1A1 His and CYP19 (TTTA)10 was positively associated with the risk of breast cancer. Other well-established risk factors as higher estrogen exposure including total years of menstrual, early menarche etc, and women with a higher BMI and WHR were all served as independent risks. CONCLUSION: This study indicated that the polymorphisms of estrogen-metabolizing genes were related to breast cancer.

Polymorphisms of estrogen-metabolizing genes and breast cancer risk: a multigenic study.

BACKGROUND: Endogenous estrogen plays a very important role in the carcinogenesis and progression of breast cancer. The enzymes involved in the biosynthesis and metabolism of estrogen have been proposed to contribute to this effect. To examine this hypothesis, we conducted a case-control study to investigate the relationship between polymorphisms of genes responsible for estrogen biosynthesis (CYP17, cytochrome P450c17a and CYP19, aromatase cytochrome P450) and estrogen sulfation of inactivation (SULT1A1, sulfotransferase1A1) and the risk of breast cancer in Chinese women. METHODS: This study involved 213 breast cancer patients and 430 matched controls. PCR-based restriction fragment length polymorphism (RFLP) and short tandem repeat polymorphism (STRP) assays were used to detect the mononucleotide transition of CYP17 and SULT1A1 and tandem repeat polymorphism of CYP19. Logistic regression analyses were used to determine OR and 95% CI of each and all three high-risk genotypes, of all three genotypes combined, and of estrogen exposure factors. The relationship between each high-risk genotype and clinicalpathological characteristics were also assessed. RESULTS: The frequency of A2 allele of CYP17 was 49.8% in cases and 49.1% in controls (P = 0.82). The frequency of His allele of SULT1A1 was significantly higher in cases (13.6%) than in controls (9.5%) (P < 0.05). There was also significant difference of the (TTTA) 10 allele of CYP19 which was 12.4% in cases and 8.2% in controls (P < 0.05). When the CYP17 A2 allele, CYP19 (TTTA) 10 and SULT1A1 His allele were considered as the "putative high-risk" genotype, there was an increased risk of breast cancer with the number of high-risk genotypes in a dose-response effect (trend, P = 0.05). In multivariate analysis, the SULT1A1 genotype remained the most significant determinant for breast cancer, with OR = 2.37 (95% CI 1.23-4.74), followed by CYP19, with OR = 1.75 (95% CI 1.27-3.56). The (TTTA) 10 allele of CYP19 was associated with tumor size, and the His allele of SULT1A1 associated with status of lymph node metastasis. CONCLUSIONS: This study supports the hypothesis that breast cancer can be initiated by estrogen exposure and that estrogen metabolizing genes are involved in this mechanism. This multigenic model is useful for identifying individuals who are at higher risks of breast cancer.

[A case-control study on the risk of female breast cancer in Wuhan area].

OBJECTIVE: To investigate the risk factors of female breast cancer and its potential alteration in Wuhan area. METHODS: A case-control study was conducted on 213 cases with histopathological diagnosis and 430 matched controls, using conditional logistic regression analysis. RESULTS: 28 factors such as educational level, history of benign breast disease, age at menarche, age at menopausal, meat and well-done meat intake, soy bean food, fruit, lactation time, body mass index (BMI), juvenile chest X-ray, psychological factor, were associated with breast cancer risk in one-way variance model. Multivariate conditional logistic regression analysis in total significant factors and subgroups showed that the risk factors of breast cancer would include high level education, psychological trauma, history of benign breast disease later age at menopause, more years of menstrual and more years of menstrual before giving first birth, high BMI, well-done meat intake and smoked food. Factors as later menarche, lactate longer, soybean food, fruit, drink tea habit were protective factors for breast cancer. Further breakdown of data showed some difference between premenopausal and postmenopausal women. Risks in premenopausal women were associated with history of benign breast disease, age of menarche, soybean food intake, whereas risks in postmenopausal women were related to age of menopausal, BMI, waist-hip ratio and fruit intake. Both psychological traumatic and duration of lactation were common pre-and postmenopausal risk and protective factors. CONCLUSIONS: Dietary habit and endogenous estrogen exposure related factors played important roles on women breast cancer in Wuhan area.

[Interaction of ApoE and LDL-R gene polymorphisms and alcohol drinking and smoking on coronary heart disease].

OBJECTIVE: To investigate the association between the ApoE and LDLR-R gene loci on coronary heart disease (CHD) and their interaction with alcohol drinking and smoking in Hans of Chinese. METHODS: A questionnaire survey of the behaviors of smoking and drinking, dietary custom, and anamnesis, was conducted among 146 cases of CHD, aged 64 +/- 11, and 340 controls, aged 63 +/- 12. Peripheral blood samples were collected and the total DNAs were extracted. The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were examined. The ApoE genotype was identified by the method of multiplex amplification refractory mutation system and AvaII polymorphisms of the LDL-R gene were detected by using the method of polymerase chain reaction-restriction fragment length polymorphism. The interaction between the genes and alcohol drinking and smoking was analyzed by using multivariate logistic regression models. RESULTS: (1) Both the systolic blood pressure and diastolic blood pressure of the CHD patients (132 mm Hg +/- 21 mm Hg, and 81 mm Hg +/- 13 mm Hg, 1 mm Hg = 0.133 kPa) were significantly higher than those of the controls (123 mm Hg +/- 17 mm Hg and 77 mm Hg +/- 11 mm Hg, both P < 0.05). The level of TG was 1.6 +/- 0.9 mmol/L in the CHD group, significantly higher than that in the control group (1.4 +/- 0.8 mmol/L, P < 0.05). However, there was no difference in the levels of TC, LDL-C, and HDL-C between the 2 groups (all P > 0.05). (2) For the ApoE gene, the frequencies of E4/3 genotype and epsilon 4 allele were 24.0% and 13.4% respectively in the CHD group, both significantly higher than those in the control group (12.9% and 7.2% respectively, both P < 0.05). For the LDLR-AvaII locus, no difference was found in different genotypes between the CHD and control groups. However, the proportion of those with epsilon 4 locus and AvaII(+) locus simultaneously was 60% in the CHD group, significantly higher than in the control group (31.8%, P < 0.05). (3) After adjustment of confounding variables, such as age, sex, blood pressure, and body mass index, the binary logistic analysis showed a significant gene-environment interaction (P < 0.05). The OR value were: for epsilon 4-AvaII(+): 2.99 (95% CI: 1.36 approximately 6.66, P < 0.01), for epsilon 3-often drinking: 2.60 (95% CI: 1.35 approximately 5.02, P < 0.01), for epsilon 3-smoking 2.58 (95% CI: 1.16 approximately 5.71, P < 0.05), for epsilon 4-stopped smoking 3.12 (95% CI: 1.23 approximately 8.09, P < 0.05), for epsilon 4-smoking: 5.30 (95% CI: 1.21 approximately 23.22, P < 0.05), and for AvaII(+)-often drinking: 2.49 (95% CI: 1.12 approximately 5.52, P < 0.05) respectively. CONCLUSION: The carriers of epsilon 3, epsilon 4 or AvaII(+) alleles would have higher risk of suffering from CHD if they are drink alcohol or smoke heavily.

Sulfotransferase 1A1 (SULT1A1) polymorphism and breast cancer risk in Chinese women.

BACKGROUND: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, catalyzes the sulfation of a variety of phenolic and estrogenic compounds. A functional polymorphism of the SULT1A1 gene has been implicated in a decreased activity and thermostability when the wild-type arginine (Arg) at codon 213 is substituted by a histidine (His). METHODS: We investigated the association between the His allele and the risk breast cancer in 213 cases and 430 matched controls in Chinese women, and the interaction between His allele and endogenous estrogen and dietary mutagens exposure factors were also determined by use of logistic regression analysis. RESULTS: There was no significant difference in genotypes between the cancer patients and control populations. However, the frequency of the His allele in cases (13.6%) were significant higher than that in controls (9.5%), P = 0.03. Compared with women carrying the Arg/Arg genotype, the adjusted odds ratio (OR) of Arg/His was 1.48 (95% CI = 0.59-3.31) and His/His was 2.28 (95% CI = 0.69-9.58), P trend was 0.04. The adjusted OR of Arg/His + His/His was 2.60 (95% CI = 1.12-6.05). His allele strengthen the effect of endogenous estrogen exposure with interaction index r > 1, and weaken the effect of heterocyclic amines and polycyclic aromatic hydrocarbons derived from dietary with interaction index r > 1, both were multiplicative interaction model. CONCLUSIONS: Our findings suggest that the SULT1A1 His allele was positively associated with the risk of breast cancer in Chinese women. And there was interaction between SULT1A1 polymorphism and related exposure factors.

[Genetic association of apoE and apoCI gene polymorphisms with coronary heart disease].

OBJECTIVE: To study the genetic association of apolipoprotein (apo) E and apoCI gene polymorphisms with coronary heart disease (CHD) in China. METHODS: apoE genotypes were identified by multiplex amplification refractory mutation system (multi-ARMS) and the apoCI promoter polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 186 cases with CHD (age: 65.0 +/- 10.5 years) and 350 controls (age: 63.6 +/- 8.3 years). The haplotype frequencies were estimated. RESULTS: The frequencies of apoE E4/3 genotype (26.9%) and epsilon4 (14.5%) in CHD group were significantly higher than that in the control group (12.6%, 7.0%), P <0.05. The significant difference was also found for the apoCI locus and the CHD group showed higher rate of both for the H2 allele and genotypes, carrying this allele. Estimation of the haplotype frequencies indicated that the association between the apoE-CI haplotype and CHD was significantly strong. The apoE-epsilon4/apoCI-H2 was estimated to be responsible for 9.86% of CHD. CONCLUSION: When the subjects carrying both epsilon4 and H2 alleles, they would have higher risk of suffering from CHD than controls.

[The association of sulfotransferase1A1 His allele and breast cancer in Han ethnic Chinese women].

OBJECTIVE: To assess the relationship between SULT1A1 Arg213His polymorphism and breast cancer in Hans of Chinese women, as well as the interaction of the polymorphism and related risk factor of breast cancer. METHODS: Distribution of Arg213His polymorphism of the SULT1A1 gene was detected by using PCR-RFLP in 209 cases of breast cancer and 426 matched healthy controls. The OR of susceptibility of SULT1A1 genotypes to breast cancer and the r value of interaction with exposure factors using multivariate logistic regression. RESULTS: (1) There was no significant difference in genotype of Arg/Arg, Arg/His and His/His of SULT1A1 between case and control (P = 0.12). The frequency of His allele was 13.6% and 9.5% in were determined case and control, respectively, P = 0.03; (2) Compared with Arg/Arg genotype, the risk of Arg/His and His/His was increased, P for trend = 0.04; The OR of His allele (Arg/His + His/His) was 2.60 (95% CI: 1.12 - 6.05, P = 0.04); (3) As for the interaction between gene and related exposure factors, His allele strengthen the effect of endogenous estrogen exposure (interaction index r > 1), and weaken the effect of factors related to exposure of some procarcinogen in dietary (r < 1), both being multiplicative interaction model. CONCLUSION: SULT1A1 His allele is positively associated with the risk of breast cancer, and an interaction exist between this allele and related exposure factors.

[Diagnosis and treatment of recurrent epithelial ovarian carcinoma].

OBJECTIVE: To investigate the diagnosis, treatment and prognosis of recurrent epithelial ovarian carcinoma. METHODS: Fifty-two patients with recurrent epithelial ovarian carcinoma who were admitted in Zhongnan Hospital of Wuhan University between 1997 and 2002 were analyzed retrospectively, and their diagnostic methods and the survival rates were compared. RESULTS: The positive diagnostic rate of pelvic examination, CA(125) and ultrasound examination was 73.1%, 84.6% and 53.8%, respectively to the recurrent epithelial ovarian carcinoma. The median survival time of group A (surgery + chemotherapy) and group B (chemotherapy) was 11 and 12 months, respectively. CONCLUSIONS: The diagnostic methods should include pelvic examination, CA(125) and ultrasound examination. We could not know the exact role of surgery to the management and prognosis of recurrent epithelial ovarian carcinoma. Chemotherapy may have an important role to the management and prognosis of recurrent epithelial ovarian carcinoma.