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ABSTRACT: The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M and GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.
Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(4):2221-2224. · 0.66 Impact Factor
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ABSTRACT: TP53, located on chromosome 17p13, is one of the most mutated genes affecting many types of human cancers. Thus, we aimed at investigating the association of SNPs in TP53 gene with chronic myeloid leukemia (CML).
A total of 236 CML and 157 control samples were analysed for mutations in TP53 gene using polymerase chain reaction followed by direct sequencing.
Sequencing analysis for mutations in exons 7-9 of the TP53 gene revealed four SNPs, three in intron 7 (C14181T, T14201G, and C14310T) and one SNP in intron 6 (A13463G) of TP53 gene. The mutation C14181T is located at position 72 base pairs downstream of the 3'-end of exon 7 of the P53 gene. This mutation is in complete linkage disequilibrium with a T14201G mutation, 20 base pairs further downstream occurring at position 14201. This mutation occurred only in the presence of C14181T mutation and these mutations showed association with advanced phase and cytogenetic poor response. Another two novel mutations, C14310T in intron 7 and A13463G in intron 6 were also found to be associated with cytogenetic poor response.
Our study suggests that TP53 intronic SNPs might have a strong influence on disease progression and poor response in CML patients.
Journal of natural science, biology, and medicine. 07/2012; 3(2):182-5.
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Journal of Genetics 04/2012; 88(2):261-266. · 1.09 Impact Factor
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ABSTRACT: TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (χ2- 133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.
Asian Pacific journal of cancer prevention: APJCP 01/2012; 13(1):347-50. · 0.66 Impact Factor
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ABSTRACT: CYP3A5 was observed to be an important genetic contributor to inter individual differences in CYP3A-dependent drug metabolism in acute leukemic patients. Loss of CYP3A5 expression was mainly conferred by a single nucleotide polymorphism at 6986A>G (CYP3A5*3). We investigated the association between CYP3A5*3 polymorphism and acute leukemia.
Two hundred and eighty nine acute leukemia cases comprising of 145 acute lymphocytic leukemia (ALL), 144 acute myeloid leukemia and 241 control samples were analyzed for CYP3A5*3 polymorphism using PCR-RFLP method. Statistical analysis was performed with SPSS version (15.0) to detect the association between CYP3A5*3 polymorphism and acute leukemia.
The CYP3A5*3 polymorphism 3/3 genotype was significantly associated with acute leukemia development (χ(2)- 133.53; df-2, P 0.000). When the data was analyzed with respect to clinical variables, mean WBC, blast % and LDH levels were increased in both ALL and AML cases with 3/3 genotype. The epidemiological variables did not contribute to the genotype risk to develop either AML or ALL.
The results suggest that the CYP3A5*3 polymorphism might confer the risk to develop ALL or AML emphasizing the significance of effective phase I detoxification in carcinogenesis. Association of the polymorphism with clinical variables indicate that the 3/3 genotype might also contribute to poorer survival of the patients.
Indian Journal of Human Genetics 09/2011; 17(3):175-8.
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Y Horikawa,
N Tsuchiya,
K Yuasa,
S Narita,
M Saito,
K Takayama,
T Nara,
H Tsuruta,
T Obara,
K Numakura, [......],
S Cai,
Z Wang,
J Xu,
W. Zhan,
Y F Zhang,
M Misumi,
H Takeuchi,
N Nakamiya,
K Matsuura,
N Fujiuchi
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ABSTRACT: BACKGROUND: Sunitinib is a new tyrosine kinase inhibitor that has shown significant clinical activity in metastatic renal cell carcinoma (mRCC). We are reporting early clinical experiences of sunitinib at Akita University Hospital to evaluate its efficacy and safety for Japanese RCC patients. METHODS: Between April 2006 and November 2009 at our institution, 21 patients with a median age of 61 years (range, 37 to 80 years) with mRCC were treated with sunitinib. Eleven (52.4%) patients received sunitinib as a first-line treatment. The efficacy of sunitinib was evaluated with Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. Progression-free survival (PFS) and adverse events (AEs) were assessed. RESULTS: At a median follow-up of 8 months (range, 1 to 43 months), our patients received an average of 6.2 cycles of sunitinib (range, 1 to 28 cycles). While no patients experienced complete response, partial response (PR) and stable disease (SD) were observed in 7 patients (28.5%) and 8 patients (38.0%), respectively; six patients (28.5%) had progressive disease (PD), median PFS was 10 months. The main grade 3/4 AEs were thrombocytopenia (47.6%), anemia (28.5%), leukocytopenia (19.0%), hand-foot syndrome (14.2%), and hypertension (14.2%). In addition to these AEs, hypothyroidism, which requires thyroid hormone replacement therapy, was noted in 14 (67.0%) patients. Seven patients discontinued sunitinib within 2 cycles (5 due to disease progression, 2 due to drug toxicities). Ten (66.7%) of 14 patients who received more than 3 cycles of sunitinib needed dose reduction during treatment. CONCLUSION: Sunitinib was effective for the treatment of mRCC in a real clinical setting, although there were several side effects that led to discontinuation of this drug. To utilize sunitinib safely and more effectively, further examination of this drug for Japanese RCC patients is necessary.
Japanese Journal of Clinical Oncology 03/2011; 41(3):i6-i17. · 1.78 Impact Factor
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ABSTRACT: The p53 protein is at the center of cell regulatory pathways influencing transcription and activity of several replication and transcription factors. In exon 4 of the gene TP53, a codon 72 polymorphism causing an Arg/Pro substitution has been reported in breast and other cancers. This substitution is in the putative SH3 binding domain of p53 protein, influencing binding capacity and thereby functional properties. In the present investigation of a relatively large series of cases in India, the frequency of the homozygous arginine genotype (33.2%) was significantly higher in the breast cancer group as compared to controls (19.6%), χ2 =11.791 (P=0.003). Patients with premenopausal breast cancer had a more elevated frequency (41.1%) than postmenopausal cases (25.4%) although the genotype frequency distribution did not show significant variation with respect to hormonal receptor status. Elevation was greatest in patients in advanced stages of cancer. The hetrozygote frequency (Arg/Pro) was also found to be increased in overweight and obese women with breast cancer. TP53 codon 72 polymorphism might predispose individual for the development of breast cancer as well as to bad prognosis. Intronic variants may affect gene regulation through aberrant splicing or through disruption of critical DNA-protein interaction. While no significant association was observed with relation to CC genotype as well as C allele of G13964C intron polymorphism with breast cancer, the C allele frequency showed association with respect to other risk confounding factors which might play role in progression of breast cancer.
Asian Pacific journal of cancer prevention: APJCP 01/2011; 12(8):1893-8. · 0.66 Impact Factor
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ABSTRACT: CYP2D6 gene plays an important role in detoxification of many drugs and plays a crucial role in the metabolism of tamoxifen, used in endocrine therapy. In the present study, the heterozygous frequency IM (40.8%) was significantly increased in breast cancer patients when compared to controls. When the data on IM and PM were pooled, significant increase in the frequency of pooled genotype in disease group (42.4%) was observed as compared to controls (27.6%). The frequency of IM genotype was found to be increased in women with premenopausal breast cancer patients (43.5%) and patients with familial history of cancer (43.2%). Higher frequency of IM as well as pooled genotypes PM+IM was found in cases with higher BMI and in patients occupied in agriculture (55.6%), patients positive for estrogen receptor (47.8%), progesterone receptor (44.8%), HER2/neu (26.9%) and advanced stage. Our results suggested that the CYP2D6*4 polymorphism plays an important role in the breast cancer etiology and might help in planning hormonal therapy where tamoxifen is used. Introduction CYP2D6 (Debrisoquine hydroxylase) is one of the most thoroughly studied enzymes, since lack of its activity is the basis for adverse events occurring during therapy with some drugs (Eichelbaum et al., 1990). This enzyme has a wide range of activity within human populations, with interindividual variation in the rates of metabolism differing more than 10,000-folds (Nebert, 1997). Most individuals are able to metabolize CYP2D6 substrates extensively (EM). About 5-10% of Caucasians have inactivating mutations in both alleles of the CYP2D6 gene that are termed as poor metabolisers (PM). CYP2D6 gene is located on chromosome 22q13.1.The most frequent inactivating mutation among Caucasians is the splice site G1934A transition (CYP2D6*4 allele) that cause a truncated protein. G to A transition at the intron3/exon4 boundary of the CYP2D6 gene leads to incorrect splicing of mRNA resulting in a frame shift and premature termination .The G to A transition had been identified as a primary defect at the CYP2D6 locus and is estimated to account for 80-90% of mutant alleles in PM (Gough et al., 1990). The biotransformation of tamoxifen which is used for the treatment of endocrine related cancer like breast, ovary etc is mediated by CYP2D6 enzymes mainly through demethylation and hydroxylation to form several primary metabolites, principally 4 OH-tamoxifen, α-OH-tamoxifen, N-desmethyl-tamoxifen and 4-OH-N-desmethyl-tamoxifen.4-OH-tamoxifen is considered to be more potent anti-estrogen than the parent substance and is capable of binding the ER with greater affinity (Jin et al., 2005). CYP2D6 polymorphism can be classified according to one of four levels of activity: poor metabolisers (PMs), intermediate metabolisers (IMs), extensive metabolisers (EMs) and ultra rapid metabolisers (UMs) (Jann et al., 2001). The EM phenotype is expressed by the majority of the population and is therefore considered as normal. PMs inherit two deficient CYP2D6 alleles; as a result, they metabolize drugs at a slower rate. This leads to an accumulation of high levels of unmetabolized drugs. The UM phenotype is caused by the duplication or amplication of active CYP2D6. Individuals with UM genotype will metabolize drugs at an ultra rapid rate, which might lead to a loss of therapeutic efficacy at standard doses. Individuals who were heterozygous for a defective CYP2D6 allele often demonstrate an IM phenotype. This phenotype had a wide spectrum of metabolic activity that can range from marginally better than the PM phenotype, to activity that is close to the EM phenotype (Meyer, 2004).
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ABSTRACT: CYP2D6 gene plays an important role in detoxification of many drugs and plays a crucial role in the metabolism of tamoxifen, used in endocrine therapy. In the present study, the heterozygous frequency IM (40.8%) was significantly increased in breast cancer patients when compared to controls. When the data on IM and PM were pooled, significant increase in the frequency of pooled genotype in disease group (42.4%) was observed as compared to controls (27.6%). The frequency of IM genotype was found to be increased in women with premenopausal breast cancer patients (43.5%) and patients with familial history of cancer (43.2%). Higher frequency of IM as well as pooled genotypes PM+IM was found in cases with higher BMI and in patients occupied in agriculture (55.6%), patients positive for estrogen receptor (47.8%), progesterone receptor (44.8%), HER2/neu (26.9%) and advanced stage. Our results suggested that the CYP2D6*4 polymorphism plays an important role in the breast cancer etiology and might help in planning hormonal therapy where tamoxifen is used. Introduction CYP2D6 (Debrisoquine hydroxylase) is one of the most thoroughly studied enzymes, since lack of its activity is the basis for adverse events occurring during therapy with some drugs (Eichelbaum et al., 1990). This enzyme has a wide range of activity within human populations, with interindividual variation in the rates of metabolism differing more than 10,000-folds (Nebert, 1997). Most individuals are able to metabolize CYP2D6 substrates extensively (EM). About 5-10% of Caucasians have inactivating mutations in both alleles of the CYP2D6 gene that are termed as poor metabolisers (PM). CYP2D6 gene is located on chromosome 22q13.1.The most frequent inactivating mutation among Caucasians is the splice site G1934A transition (CYP2D6*4 allele) that cause a truncated protein. G to A transition at the intron3/exon4 boundary of the CYP2D6 gene leads to incorrect splicing of mRNA resulting in a frame shift and premature termination .The G to A transition had been identified as a primary defect at the CYP2D6 locus and is estimated to account for 80-90% of mutant alleles in PM (Gough et al., 1990). The biotransformation of tamoxifen which is used for the treatment of endocrine related cancer like breast, ovary etc is mediated by CYP2D6 enzymes mainly through demethylation and hydroxylation to form several primary metabolites, principally 4 OH-tamoxifen, α-OH-tamoxifen, N-desmethyl-tamoxifen and 4-OH-N-desmethyl-tamoxifen.4-OH-tamoxifen is considered to be more potent anti-estrogen than the parent substance and is capable of binding the ER with greater affinity (Jin et al., 2005). CYP2D6 polymorphism can be classified according to one of four levels of activity: poor metabolisers (PMs), intermediate metabolisers (IMs), extensive metabolisers (EMs) and ultra rapid metabolisers (UMs) (Jann et al., 2001). The EM phenotype is expressed by the majority of the population and is therefore considered as normal. PMs inherit two deficient CYP2D6 alleles; as a result, they metabolize drugs at a slower rate. This leads to an accumulation of high levels of unmetabolized drugs. The UM phenotype is caused by the duplication or amplication of active CYP2D6. Individuals with UM genotype will metabolize drugs at an ultra rapid rate, which might lead to a loss of therapeutic efficacy at standard doses. Individuals who were heterozygous for a defective CYP2D6 allele often demonstrate an IM phenotype. This phenotype had a wide spectrum of metabolic activity that can range from marginally better than the PM phenotype, to activity that is close to the EM phenotype (Meyer, 2004).
Biology and Medicine. 01/2010;
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Asian Pacific journal of cancer prevention: APJCP 01/2010; · 0.66 Impact Factor
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ABSTRACT: CYP3A5 is a member of the CYP3A gene family which metabolizes 50% of therapeutic drugs and steroid hormones. CYP3A5*3 and CYP3A5*6 polymorphisms exhibit inter-individual differences in CYP3A5 expression. The CYP3A5*3 allele (A6986G transition in intron 3) results in loss of CYP3A5 expression and the CYP3A5*6 allele (G14690A transition in exon 2, leading to the skipping of exon 7) is associated with lower CYP3A5 catalytic activity. The aim of the present study was to investigate their influence on susceptibility to chronic myeloid leukemia (CML). 265 CML cases and 241 age and sex matched healthy controls were analyzed by the PCR-RFLP technique. The frequencies of homozygous 3/3 genotype and CYP3A5*3 allele were elevated significantly in the CML group compared to controls (χ²=93.15, df=2, p=0.0001). With respect to clinical parameters, CYP3A5*3 allele frequency was increased in patients with advanced phase of the disease (0.71) as compared to those in chronic phase (0.65). Patients without hematological response (minor/poor) had higher frequency of 3/3 genotype (54.54%) as compared to those with major hematological response (41.2%). CYP3A5*6 allele was not observed in cases as well as in controls. Our study suggests that the CYP3A5*3 gene polymorphism is significantly associated with the risk of CML development and disease progression.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(3):781-4. · 0.66 Impact Factor
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ABSTRACT: The multidrug resistance (MDR1) gene product P-glycoprotein is a membrane bound protein that functions as an ATP-dependent efflux pump, transporting exogenous and endogenous substrates from the cells. Since it plays an important role in chemotherapy, there is an increasing interest in the possible significance of genetic variation in MDR1. Our main objective was to study the MDR1gene polymorphism at C3435T with reference to development and progression of acute leukemia. The present study included 290 acute leukemia cases, comprising of 147 acute lymphocytic leukemia (ALL), 143 acute myeloid leukemia and 249 age-sex matched control samples for the analysis of MDR1 C3435T polymorphism, by the PCR-RFLP method. The MDR1 genotype distribution revealed an elevated frequency of the TT genotype in ALL cases (51.7%) as compared to controls (28.9%), whereas AML group did not show any association. The mean white blood cell count, blast% and LDH levels were increased in ALL patients with the CC genotype. No deviation was observed with respect to hematoglobin, platelet count and disease free survival in ALL patients. The association of CC genotype with clinical variables in ALL indicated that the CC genotype with high expression might be eliminating antileukemic drugs (anthracyclines, Daunorubicin, Vincristeine, Mitoxanthrone) which are P-gp substrates, leading to lower intra cellular drug concentrations and a poor prognosis. Such an association with the CC genotype was not observed in AML. In conclusion, these results suggested that the MDR1 TT genotype might influence risk of development of acute lympoblastic leukemia and the CC genotype might be linked to a poor prognosis of ALL.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(4):1063-6. · 0.66 Impact Factor
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ABSTRACT: The human CYP17 gene, located on chromosome 10q24.3, plays a key role in sex steroid synthesis, mainly related to estrogen. A 5' UTR polymorphism involving a single base pair change in the promoter region results in increased transcriptional activity. In the present study of 250 breast cancer cases and 250 ma tched controls, the A1 genotype frequency was elevated in the disease group, while the A2 genotype frequency demonstrated no association. When data were stratified by risk conferring group, however, the A2 genotype frequency was increased in postmenopausal breast cancer cases (4.2%), patients positive for a family history of breast cancer (5.5%), high BMI, estrogen receptor (6.2%) and progesterone receptor negative (5.0%) status, HER2/neu positive (7.7%) status, positive node status (5.0%) as well as advanced stage of the disease. The A1A1 genotype linked with increased production of androgens might impact on onset of breast cancer while the A2 allele showed associations with respect to important risk conferring parameters.
Asian Pacific journal of cancer prevention: APJCP 01/2010; 11(6):1653-7. · 0.66 Impact Factor
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Journal of Genetics 09/2009; 88(2):261-6. · 1.09 Impact Factor
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ABSTRACT: The Cytochrome P-4501A1 (CYP1A1) gene, located on chromosome 15q, is involved in the metabolism of carcinogens mainly polycyclic aromatic hydrocarbons as well as estrogen. It is considered as candidate gene for low-penetrance breast cancer susceptibility. Hence the present study aims to discuss the role of CYP1A1 polymorphisms in breast cancer.
A total of 250 breast cancer patients and the same number of healthy age-matched controls were analyzed for the polymorphism of CYP1A1*2 by polymerase chain reaction-restriction fragment length polymorphism.
In the present study, association of CYP1A1*2 (Ile 462Val) polymorphism with breast cancer was studied. Only one breast cancer patient was observed to be homozygous for Val allele but none among controls. The frequency of heterozygous Ile/Val genotype was found to be increased significantly in breast cancer patients (68.1%) as compared to controls (51.0%). Higher frequency of heterozygotes for Val allele was observed among premenopausal breast cancer patients and patients with high BMI, positive for HER2/neu status and advanced stage of the disease in comparison to the corresponding groups. No significant association of CYP1A1*2 polymorphism was observed with occupation, estrogen receptor and progesterone receptor status of breast cancer patients.
In conclusion, our results suggest a significant correlation between CYP1A1*2 expression and the occurrence of breast cancer.
Indian Journal of Medical Sciences 02/2009; 63(1):13-20.
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ABSTRACT: Background : The Cytochrome P-4501A1 (CYP1A1) gene, located on chromosome 15q, is involved in the metabolism of carcinogens mainly polycyclic aromatic hydrocarbons as well as estrogen. It is considered as candidate gene for low-penetrance breast cancer susceptibility. Hence the present study aims to discuss the role of CYP1A1 polymorphisms in breast cancer. Materials and Methods : A total of 250 breast cancer patients and the same number of healthy age-matched controls were analyzed for the polymorphism of CYP1A1FNx012 by polymerase chain reaction-restriction fragment length polymorphism. Results : In the present study, association of CYP1A1FNx012 (Ile 462Val) polymorphism with breast cancer was studied. Only one breast cancer patient was observed to be homozygous for Val allele but none among controls. The frequency of heterozygous Ile/Val genotype was found to be increased significantly in breast cancer patients (68.1%) as compared to controls (51.0%). Higher frequency of heterozygotes for Val allele was observed among premenopausal breast cancer patients and patients with high BMI, positive for HER2/neu status and advanced stage of the disease in comparison to the corresponding groups. No significant association of CYP1A1FNx012 polymorphism was observed with occupation, estrogen receptor and progesterone receptor status of breast cancer patients. Conclusions : In conclusion, our results suggest a significant correlation between CYP1A1FNx012 expression and the occurrence of breast cancer.
Indian Journal of Medical Sciences. 01/2009;
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ABSTRACT: Estrogen receptor (ER) is a ligand-inducible transcription factor that mediates estrogen action in target tissue. Several common polymorphisms of the ERα gene have been reported to be associated with alterations in receptor expression in breast cancer.
A case-control study was designed to compare 250 breast cancer patients with 250 age-matched healthy controls. The frequency distribution of PvuII polymorphism in the ERα gene was assessed by PCR-RFLP method.
The frequency of the PP genotype (35.3%) was increased significantly in breast cancer patients when compared to controls (19.8%), with a corresponding increase in P allele frequency (χ(2)= 16.4; P = 0.0003). The OR for genotypes PP vs. Pp was 1.989 (95% CI: 1.2708 to 3.113). Premenopausal women with breast cancer had an elevated frequency of the PP genotype (22.8%) as compared to postmenopausal women (16.8%). The frequency of the PP genotype was increased in patients positive for ER and HER-2/neu as compared to those with receptor-negative status. The pp and p allele frequencies were increased in progesterone-receptor-negative status. When stage of the disease was considered, both Pp and pp genotype frequencies were elevated in patients with advanced stage breast cancer. The frequency of the P allele and PP genotype frequencies tended to increase with increase in body mass index, whereas the Pp genotype frequency was elevated only in obese patients. The reverse was observed in the case of pp genotype frequency.
The study thus highlighted the influence of ERα PvuII polymorphism on the development and progression of breast cancer.
Indian Journal of Human Genetics 09/2007; 13(3):97-101.
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ABSTRACT: Background: Estrogen receptor (ER) is a ligand-inducible transcription factor that mediates estrogen action in target tissue. Several common polymorphisms of the ERα gene have been reported to be associated with alterations in receptor expression in breast cancer. Materials and Methods: A case-control study was designed to compare 250 breast cancer patients with 250 age-matched healthy controls. The frequency distribution of PvuII polymorphism in the ERα gene was assessed by PCR-RFLP method. Results: The frequency of the PP genotype (35.3%) was increased significantly in breast cancer patients when compared to controls (19.8%), with a corresponding increase in P allele frequency (χ<sup>2</sup> = 16.4; P = 0.0003). The OR for genotypes PP vs. Pp was 1.989 (95% CI: 1.2708 to 3.113). Premenopausal women with breast cancer had an elevated frequency of the PP genotype (22.8%) as compared to postmenopausal women (16.8%). The frequency of the PP genotype was increased in patients positive for ER and HER-2/neu as compared to those with receptor-negative status. The pp and p allele frequencies were increased in progesterone-receptor-negative status. When stage of the disease was considered, both Pp and pp genotype frequencies were elevated in patients with advanced stage breast cancer. The frequency of the P allele and PP genotype frequencies tended to increase with increase in body mass index, whereas the Pp genotype frequency was elevated only in obese patients. The reverse was observed in the case of pp genotype frequency. Conclusion: The study thus highlighted the influence of ERα PvuII polymorphism on the development and progression of breast cancer.
Indian Journal of Human Genetics. 01/2007;
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ABSTRACT: Cell surface molecules, NCAM and L1, reported to have a role in synaptogenesis, growth and fasciculation of the neurites in the brain, were traced in the embryonic nigral transplants in the host striatum of adult rats. Substantia nigra of five, 15 and 25 postnatal days were also examined for the same molecules. Tyrosine hydroxylase label was used as a marker to localize the nigral neurons and glial fibrillary acidic protein to detect if glial scar present. In the control as well as transplants large neurons had expressed tyrosine hydroxylase. By 15th postnatal day tyrosine hydroxylase neurons appeared mature and were scattered, suggesting a well-formed neuropil. NCAM and L1 reaction was seen as a peripheral rim in most of the cells on the fifth postnatal day. The reaction was mainly in relation to the large cells and more extensive on the 15th day. Thereafter on the 25th day, activity was negligible. Large neurons demonstrated strong reactivity for NCAM and L1 during early post-transplantation days. After 30 days only smaller cells were reactive, many of which could be identified as neurons. Strong reaction for these molecules was present only until 60 days, though faint reaction could be detected even on the 90th day. These observations indicate that the growth promoting molecules, the type seen in the neonatal period, can be detected normally only until the neurons mature. Prolonged expression of these molecules by the grafted neurons indicate delay in the maturation of these cells due to absence of adequate target sites for synaptic connections. Some of the smaller cells expressing these molecules after 30 days of transplantation could be astroglia, either proliferating or reactive.
Neuroscience.
