Dwivedi, Shipra
(Department of physiology, King George's Medical University)
,
Agrawal, Sarita
(Department of physiology, King George's Medical University)
,
Singh, Shraddha
(Department of physiology, King George's Medical University)
,
Madeshiya, Amit Kumar
(Department of physiology, King George's Medical University)
,
Singh, Devendra
(Department of physiology, King George's Medical University)
,
Mahdi, Abbas Ali
(Department of physiology, King George's Medical University)
,
Chandra, Abhjeet
(Department of physiology, King George's Medical University)
Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism an...
Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.
Background: Cholelithiasis is associated in 54%-98% of patients with carcinoma of the gallbladder, and a high incidence among females suggests a role of female hormones in the etiology of the disease. Cytochrome $P450C17{\alpha}$ (CYP-17) is a key enzyme involved in estrogen metabolism and polymorphisms in CYP-17 are associated with altered serum levels of estrogens. Thus, we investigated whether the CYP-17 MspA1 gene polymorphism might impact on risk of gall bladder cancers or gallstones, as well as to determine if this gene polymorphism might be linked with estrogen serum levels and lipid profile among the North Indian gall bladder cancer or gallstone patients. Materials and Methods: CYP-17 gene polymorphisms (MspA1) were genotyped with PCR-RFLP in cancer patients (n=96), stone patients (n=102), cancer + stone patients (n=52) and age/sex matched control subjects (n= 256). Lipid profile was estimated using a commercial kit and serum estrogen was measured using ELISA. Results: The majority of the patients in all groups were females. The lipid profile and estrogen level were significantly higher among the study as compared to control groups. The frequency of mutant allele A2 of CYP17 MspA1 gene polymorphism was higher among cancer (OR=5.13, 95% CI+3.10-8.51, p=0.0001), stone (OR=5.69, 95%CI=3.46-9.37, p=0.0001) and cancer + stone (OR=3.54, 95%CI=1.90-6.60, p=0.0001) when compared with the control group. However there was no significant association between genotypes of CYP17 MspA1 gene polymorphism and circulating serum level of estrogen and lipid profile. Conclusions: A higher frequency of mutant genotype A1A2 as well as mutant allele A2 of CYP-17 gene polymorphism is significantly associated with risk of gallbladder cancer and stones. Elevated levels of estrogen and an altered lipid profile can be used as predictors ofgall bladder stones and cancer in post menopausal females in India.
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대상 데이터
Subjects were recruited with written informed consent from department of General Surgery, Gastroenterology, King George’s Medical University, Uttar Pradesh, Lucknow, India. Total 506 subjects (n=250 cases and n=256 control subjects) between the age group of 18 to 70 years were enrolled in study on the basis of well defined inclusion and exclusion criteria. The sample size was statistically calculated with 90% of power.
데이터처리
The one way analysis of variance (ANOVA) was used to compare the means among the groups with Tukey’s pair wise comparison test for normally distributed variables.
이론/모형
The one way analysis of variance (ANOVA) was used to compare the means among the groups with Tukey’s pair wise comparison test for normally distributed variables. Kruskall-Walis test was used to compare non-normal data. The multivariate binary logistic regression analysis was carried out to find the risk factors for cancer, stone, and cancer+stone patients compared with controls.
Low density lipoprotein (LDL) and Very low density lipoprotein (VLDL) was calculated using the Friedewald Formula [LDL= TC-(HDL+VLDL) & VLDL= TG/5] (Friedewald et al., 1972).
The results are presented as mean±SD and percentages. The chi-square test was used to compare dichotomous/categorical variables among the groups and Hardy-Weinberg equilibrium testing. The one way analysis of variance (ANOVA) was used to compare the means among the groups with Tukey’s pair wise comparison test for normally distributed variables.
성능/효과
05) difference in the lipid and estrogen levels between the wild and heterozygous genotype of CYP-17 gene polymorphism among the all groups. However, among the controls only TG and VLDL were significantly different between the wild and heterozygous genotype of CYP-17 gene polymorphism (Table 3).
05) difference between the Cancer and Stone group as well as Cancer and Cancer + Stone groups. The comparison between stone and cancer + stone group shows that the level of TC, TG, LDL, VLDL, estrogen was significantly (p=0.0001) higher and HDL was significantly lower among cancer+stone group. Similarly the comparison of cancer, stone and cancer+stone (all study group) with the control group shows that the level of TC, TG, LDL, VLDL, estrogen was significantly higher and HDL was significantly lower among the all study groups.
Interestingly, between the groups analysis, there was no significant difference of lipid level between the Cancer and Stone group as well as Cancer and Cancer + Stone groups. The comparison between stone and cancer + stone group shows that the level of TC, TG, LDL, VLDL, estrogen was significantly higher and HDL was significantly lower among cancer+stone group. Similarly, the comparison between the all study group (cancer, stone and cancer+stone) and control group shows that the level of TC, TG, LDL, VLDL, estrogen was significantly higher and HDL was significantly lower among the all study groups.
The findings of our study were agreement with these reports, as in our study the serum level of total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein was found significantly higher in all study group, and high density lipoprotein was significantly lower in study group compared with control subjects.
Lipid profile and estrogen level among the study and control group: The lipid profile and estrogen level were significantly different among the groups. The serum level of total cholesterol, triglycerides, low density lipoprotein, very low density lipoprotein, estrogen were significantly higher and the serum level of high density lipoprotein were significantly lower among all the study groups as compared with controls. (Table 1)
후속연구
The specific role of CYP-17 gene polymorphism in estrogen synthesis and metabolism is still unclear. Therefore we planned the study, to see the association of CYP-17 MspA1 gene polymorphism with risk of gall bladder cancers or gallstones, as well as, as well as, to see whether this gene polymorphism associated with estrogen serum level and lipid profile among the North Indian gall bladder cancers or gallstone patients.
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