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Results for “polymorphisms”

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PubMed2001

[Analysis of association between gene polymorphisms of microsomal epoxide hydrolase (EPHX1) and infant birthweight].

We investigated association between genetic polymorphisms of EPHX1 in mother and infant birthweight. Data of 342 female workers were collected in textile mill. A total of 342 mothers were genotyped for the His139Arg polymorphism of EPHX1 by a polymerase chain reaction-restriction fragment length polymorphism assay. Using multiple linear regression models, we estimated the adjusted association between polymorphisms of EPHX1 and birthweight, with adjusted for potential confounders. We found that polymorphisms of EPHX1 were closely associated with reduced birthweight (beta +/- SE = -149 g +/- 56, P = 0.0083) after adjustment for major cofounders. In subgroup of passive smoking analysis, the polymorphisms of EPHX1 were highly associted with birthweight for those with passive smoking (beta +/- SE = -234 g +/- 88, P = 0.0088); The significant association of EPHX1 polymorphisms with reduced birthweight were showed for those with working stress (beta +/- SE = -157 g +/- 59, P = 0.0079). Our data provide polymorphisms of EPHX1 in mothers were significant association with birthweight of their infant, and showed gene-environmental interaction in relation to birthweight.

Birth Weight↗

PubMed2001

Plasminogen activator inhibitor 1 (PAI-1) levels and gene promoter polymorphisms in subjects with colorectal cancer.

The high level of plasminogen activator inhibitor 1 (PAI-1) in colorectal cancer predicts poor prognosis for patients. The insertion (5G)/deletion (4G) polymorphism (the 4G/5G polymorphism) and G-->A single base substitution (the G/A polymorphism) located at promoter of PAI-1 gene may have functional significance in regulation of its expression. In the present work the level of PAI-1, distribution of genotypes and frequency of alleles of the 4G/5G and G/A polymorphisms in samples of cancer tissue and normal mucosa as well as in blood were investigated. Blood, tumor and normal tissues were obtained from 40 patients with colorectal cancer. The 4G/5G and G/A polymorphism were determined by PCR amplification using the allele specific primers. The PAI-1 level was measured by enzyme linked immunosorbent assay (ELISA). The distribution of the genotypes of both polymorphisms did not differ significantly (p > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distributions and allele frequencies between blood, normal mucosa samples and cancer tissue. The 4G/5G and G/A polymorphisms were in linkage disequilibrium. The average level of PAI-1 in tumor samples was significantly (p < 0.05) higher than in normal tissue. The results obtained indicate that a higher level of PAI-1 can be associated with colorectal cancer. On the other hand, in colon cancer, the 4G/5G and G/A polymorphisms are not linked with elevated levels of PAI-1 and therefore may not be used to predict colon cancer prognosis.

Adult↗

PubMedDate not supplied

Polymorphisms of angiotensin-converting enzyme and angiotensin II receptor type 1 genes in essential hypertension in a Polish population.

BACKGROUND: The angiotensin-converting enzyme gene and the angiotensin II type 1 receptor gene meet the criteria for candidate genes in the pathogenesis of essential hypertension. The aim of this study was to assess the possible association between polymorphisms of these genes and essential hypertension in a Polish population, to evaluate them as possible genetic markers of susceptibility to hypertension, and to search for interaction between the two polymorphisms. MATERIAL AND METHODS: The insertion/deletion polymorphism at the angiotensin-converting enzyme gene locus and the A1166C polymorphism at the angiotensin II type 1 receptor gene locus were detected using the polymerase chain reaction and restriction fragment length methods. 250 patients with stable essential hypertension lasting at least 1 year were compared to 150 individuals without signs and symptoms of cardiovascular disease or family history of hypertension. RESULTS: No association was found between the insertion/deletion polymorphism at the angiotensin-converting enzyme locus and essential hypertension in the study population, although the DD genotype occurred more often (p<0.01) among patients with hypertension and a negative family history of hypertension than among hypertensives with a positive family history. There was an association in our study population between hypertension and the A1166C polymorphism at the angiotensinogen II type 1 receptor gene locus. The frequency of occurrence of the C1166 variant was higher among patients with hypertension (0.29) than in control subjects (0.20). The CC genotype occurred more frequently among hypertensives (0.10) than in the control group (0.04). Both these differences were statistically significant. This association was stronger in males, patients with a negative family history of hypertension, and non-obese patients with a body mass index less than 26 kg/m2. To test the interaction between the polymorphisms in question, the distribution of the A1166 and C1166 variants among ACE genotypes was assessed. The A1166 variant occurs more often among DD genotype normotensives. CONCLUSIONS: There was no association in our study population between essential hypertension and the I/D polymorphism at the angiotensin-converting enzyme gene locus. The C1166 variant of the angiotensin II type 1 receptor gene was associated with hypertension in our study population, while the A1166 variant seems to be protective as regards susceptibility to hypertension.

Alleles↗

PubMed1999

Relationship between bone mineral density and polymorphism of the estrogen receptor gene in healthy postmenopausal women in China.

OBJECTIVE: To investigate the possible relationship between bone mineral density and polymorphism of the estrogen receptor (ER) gene in Shanghai healthy postmenopausal women. METHODS: 250 unrelated healthy postmenopausal women were selected for bone mineral density (BMD) determination by Dual energy X-ray absorptiometry (DEXA) and polymorphism of estrogen receptor gene analyses by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Pvu II polymorphisms of ER gene was associated with low Troch BMD (P = 0.0153) while there was no significant relationship between Xba I polymorphism of ER gene and BMD at any of skeletal sites included in the present study, and the combination of Pvu II and Xba I polymorphisms of ER gene was significantly associated with both low Lumbar 2-4 (P = 0.0369) and Troch (P = 0.0384) BMD. Multiple stepwise regression analysis also indicated that two combined polymorphisms were correlated significantly with Lumbar 2-4 BMD (P = 0.0254) while this correlation was not revealed at any other skeletal sites. CONCLUSION: There is significant relationship between the polymorphism of ER gene and both Lumbar 2-4 BMD and Troch BMD. It is significant to explore the pathogenesis of osteoporosis and to prevent the development of osteoprosis by use of molecular genetics.

Absorptiometry, Photon↗

PubMed2002

Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer.

Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk.

Adult↗

PubMed2002

The relationship among apolipoprotein(a) polymorphisms, the low-density lipoprotein receptor-related protein, and the very low density lipoprotein receptor genes, and plasma lipoprotein(A) concentration in the Czech population.

Increased plasma concentration of lipoprotein(a) [Lp(a)] is an established independent risk factor for coronary artery disease (CAD), which is strongly genetically determined. This study was designed to investigate the relationship between the K-IV and (TTTTA)n apolipoprotein(a) [apo(a), protein; APOA, gene] polymorphisms, as well as the C766T low-density lipoprotein receptor-related protein (LRP) and the (CGG)n very low density lipoprotein receptor (VLDLR) polymorphisms on the one hand, and plasma Lp(a) levels in Czech subjects who underwent coronary angiography on the other hand. The lengths of the alleles of the APOA K-IV and (TTTTA)n polymorphisms were strongly inversely correlated with plasma Lp(a) levels in univariate analysis (r = -0.41, p < 10(-4) and r = -0.20, p < 0.01, respectively). Multivariate analysis revealed significant associations between the APOA polymorphisms studied and plasma Lp(a) levels in subjects expressing only one APOA K-IV allele (p < 10(-6) for K-IV and p < 0.001 for TTTTA). In subjects expressing both APOA K-IV alleles, the multivariate analysis revealed that only the APOA K-IV alleles were inversely correlated with plasma Lp(a) levels (p < 0.001). Associations between both the LRP and VLDLR gene polymorphisms and plasma Lp(a) levels were only of borderline significance (p < 0.06 and p < 0.07, respectively) and were not confirmed in multivariate analysis. In conclusion, both APOA length polymorphisms significantly influenced plasma Lp(a) concentration in the Czech population studied, and this circumstance could explain the association in this population observed earlier between APOA (TTTTA)n polymorphism and CAD (Benes et al. 2000). Only a minor role in the regulation of plasma Lp(a) levels is suggested for the C766T LRP and the (CGG)n VLDLR polymorphisms.

Alleles↗

PubMed2002

[Relation of polymorphism of genes controlling endothelial function and blood pressure and the occurrence of vascular complications in type 2 diabetes].

Genetic polymorphisms of factors regulating the function of endothelium and blood pressure are recently intensively studied also in type 2 diabetes because endothelial dysfunction and arterial hypertension are risk factors of atherosclerosis. The following review deals with relations of polymorphisms in the renin-angiotensin-aldosterone (RAAS) system, polymorphisms of NO-synthase (NOS) as well as the gene for atrial natriuretic peptide (hANP). So far most information was assembled on the influence of polymorphisms of RAAS genes, in particular the gene coding the angiotensin converting enzyme (ACE), on complications of type 2 diabetes. A relationship with the development of coronary disease was described in ACE genes, the receptor for angiotensin II--type 1 (AT1R), angiotensinogen and in several NOS polymorphisms. Also the relationship of polymorphisms of genes ACE, AT1R, NOS and hANP was described in relation to the development of hypertension which is an important risk factor for macrovascular and microvascular complications of diabetes. In some investigations the relationship of polymorphisms of ACE and AT1R genes and the development of diabetic nephropathy was described where a significant acceleration of the process of atherogenesis occurs. As type 2 diabetes mellitus and atherosclerosis are polygenically determinal diseases, it will be in particular necessary to investigate in future the concurrent influence of several gene polymorphisms and their interactions with the diabetic milieu intérieur on the development of macrovascular and microvascular complications of diabetes.

Angiotensinogen↗

PubMed2002

[Association of CYP2E1 of PON2311 polymorphisms in neonates with preterm].

The objective is to investigate whether Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates are associated with preterm. Using standard questionnaires, 194 singleton live born mother-neonate pairs (including preterm cases and term controls) were investigated by the trained field workers with cross-sectional survey at the hospitals in Anqing, Anhui Province, China. Epidemiological and clinical data and blood samples were obtained from 194 mother-neonate pairs. CYP2E1 homozygous wild-type (cut/cut) is not associated with a shortened gestation among neonates, compared with CYP2E1 homozygous mutant-type (uncut/uncut)/CYP2E1 heterozygote (cut/uncut) before and after adjustment confounders. However, PON2 Ser311Ser homozygote is significantly associated with a shortened gestation among neonates. When Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism were considered jointly, a significant shortened gestation was observed among neonates with the combined genotype of CYP2E1 homozygous wild-type and PON2 Ser311Ser homozygote. In conclusion, Rsa I polymorphism in the 5'-flanking region of CYP2E1 in neonates is not associated with preterm, however, PON2311 polymorphism in neonates is significantly associated with preterm. Furthermore, the gene interaction between Rsa I polymorphism in the 5'-flanking region of CYP2E1 and PON2311 polymorphism in neonates is significantly associated with preterm.

5' Flanking Region↗

PubMed2003

Haplotype analysis of the polymorphic human vascular endothelial growth factor gene promoter.

The human vascular endothelial growth factor (VEGF) gene is unusually polymorphic,and there is evidence for inheritance of conserved haplotypes. One haplotype, carrying polymorphisms at -460/+405, is associated with enhanced production of VEGF in vitro. The VEGF promoter is activated by phorbol esters and, in endometrial cells, by estrogen. We have analyzed the impact of the common -460/+405 polymorphism on both basal and stimulated VEGF transcription using the human breast cancer cell line MCF7. Because the VEGF promoter is so highly polymorphic, haplotypes were established and analyzed. Carriage of the -460/+405 polymorphisms increased basal promoter activity by 71% compared with the wild-type sequence. However, this effect was dependent on colinearity with a series of further 5' sequence polymorphisms. The -460/+405 polymorphism also increased the mean induction by phorbol ester from 5-fold to 8.5-fold. In contrast to earlier studies in endometrial cells, none of the human VEGF promoter constructs was regulated by estrogen. Overexpression of the estrogen receptor did not confer estrogen regulation to VEGF, implying cell type-specific hormonal regulation. Therefore, carriage of the -460/+405 polymorphism significantly alters VEGF promoter activity and responsiveness. This has implications for the inherited susceptibility of common diseases.

Base Sequence↗

PubMedDate not supplied

Genetic polymorphisms and susceptibility to esophageal cancer among Chinese population (review).

Esophageal cancer, which is prevalent in China and some other parts of the world, is a complex disease likely resulting from polymorphisms of multiple interacting genes and gene-environment interactions. Recent efforts have been made to analyze the associations between risk of this cancer and hereditary sequence variations in genes involved in metabolism, DNA repair and cell cycle control. We summarized here the results of published case-control studies that have examined the effects of common alleles of 15 genes, MTHFR, CYP1A1, CYP2A6, CYP2E1, GSTM1, GSTT1, GSTP1, NAT2, XRCC1, XPD, hOGG1, MGMT, p53, CNDD1 and L-Myc, on risk of esophageal squamous cell carcinoma among Chinese. Statistically significant differences in genotype frequencies found in case-control comparisons were MTHFR C677T and A1298C polymorphisms, the XRCC1 Arg194Trp polymorphisms, the hOGG1 Ser326Cys polymorphism, and the p53 Arg72Pro polymorphism. The overall effects of these genetic polymorphisms were moderate in terms of relative risk, with ORs ranging from 2-10. There was also some evidence that genetic polymorphisms in certain carcinogen-metabolizing enzymes such as CYP2E1, CYP1A1, CYP2A6, GSTM1, and GSTP1 modulate risk of the cancer, although the results require confirmation with larger sample size studies. For polymorphisms in GSTT1, XPD, CCND1, and L-Myc, the risk estimate from the studies was sufficiently precise to exclude an OR >/=1.5.

Carcinogens↗

PubMed2003

Myocardial infarction in patients aged less than 40 years. Frequency of BclI polymorphism in the fibrinogen beta-chain gene and plasma fibrinogen.

BACKGROUND: Several polymorphisms in the genes encoding for three separate chains of fibrinogen have been described. Some of them (Hae III and B854) are associated with elevated fibrinogen plasma level. AIM: To determine the frequency of BclI polymorphism in the fibrinogen beta-chain gene (BclI betaFb) in young survivors of myocardial infraction (MI) and to assess the relationship between allele status, plasma fibrinogen concentration and the number of affected coronary arteries. METHODS: The study group consisted of 99 male patients (mean age 43.5, range 29-49 years) with premature coronary artery disease (CAD) diagnosed by coronary angiography who had MI in the mean age of 37.4+/-3.2 years. The control group involved 78 age- and gender-matched healthy volunteers. DNA was extracted from peripheral blood leukocytes using standard methods. Fibrinogen blood concentration was determined using biuretic method. The BclI polymorphism in the fibrinogen beta-chain gene was investigated using polymerase chain reaction (PCR). RESULTS: Obesity was found in 15%, smoking - in 89%, hypertension - in 21%, diabetes - in 14% and hyperlipidemia - in 86% of MI patients. A family history of MI was present in 50% of patients. Coronary angiography revealed single-vessel disease in 34%, two-vessel disease in 36%, and three-vessel disease in 16% of patients. In two patients coronary angiography was normal. The frequency of BclI polymorphism of the beta-fibrinogen gene was significantly higher in MI patients than in controls (40.4% vs 29.5%, p<0.01). Moreover, in MI patients carrying the mutant allele a higher concentration of blood fibrinogen was found in comparison to patients without this anomaly (3.87 vs 3.55 g/L, p=0.05). There was no evidence of an association between the number of affected coronary arteries and polymorphism of BclI betaFbg gene status. However, all patients carrying BclI polymorphism of betaFbg gene had abnormal coronary angiography, contrary to patients without any defect. CONCLUSIONS: 1. Polymorphism of BclI betaFbg gene is associated with an increased fibrinogen plasma level. 2. There is no association between BclI polymorphism of betaFbg gene and the number of affected coronary arteries. This may confirm the hypothesis of multi-factorial aetiology of CAD in young patients suffering MI.

Adult↗

PubMed2003

[Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune liver diseases on Chinese].

OBJECTIVE: To study the association between the polymorphisms of vitamin D receptor (VDR) gene and autoimmune liver diseases and (AIH) and primary biliary cirrhosis (PBC) in Chinese. METHODS: PCR-RELP was used to investigate the polymorphisms in exon 2, and exon 7 to exon 9 of VDR among 49 AIH patients, 58 PBC patients, and 160 healthy controls, all Chinese. VDR polymorphisms were assessed by FokI, BsmI, ApaI, and TaqI endonucleases restriction fragment length polymorphism analysis after specific polymerase chain reaction (PCR) amplification. RESULTS: The distribution of VDR gene polymorphism in Chinese was similar to those in Koreans and Japanese, and different from those in the Germans and Spaniards. The percentage of ff phenotype carriers was significantly higher in the AIH patients than in the healthy controls (34.7% vs. 48.1%, chi(2) = 5.47, P = 0.019) and the percentage of Ff phenotype carriers was lower in the AIH patients than in the healthy controls (34.7% vs. 48.1%, P = 0.057). The percentage of Bb phenotype carriers was significantly lower in the PBC patients than in the healthy controls (5.2% vs. 17.5%, P = 0.021) and. the percentage of bb phenotype carriers was significantly higher in the PBC patients than in the healthy controls (94.8% vs. 80.6%, chi(2) = 6.52, P = 0.01). We also detected a significant association of the BsmI polymorphisms in PBC patients in comparison with controls (P = 0.01). Furthermore we found the difference in the FokI, BsmI, ApaI, and TaqI genotype distribution between Chinese health controls and Caucasian health controls. CONCLUSION: There is a significant association between FokI polymorphism and AIH and a significant association between the BsmI polymorphisms and PBC in Chinese.

Adult↗

PubMed2003

Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.

Tobacco smoking and occupational exposures are the main known risk factors for bladder cancer, causing direct and indirect damage to DNA. Repair of DNA damage is under genetic control, and DNA repair genes may play a key role in maintaining genome integrity and preventing cancer development. Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency may therefore be associated with bladder cancer risk. A hospital-based case-control study was conducted in Brescia, Italy, to assess the relationship between polymorphisms in DNA repair genes XRCC1 (Arg(399)Gln), XRCC3 (Thr(241)Met), and XPD (Lys(751)Gln) and bladder cancer risk. A total of 201 male incident bladder cancer cases and 214 male controls with urological nonneoplastic diseases were recruited and frequency-matched on age, period, and hospital of recruitment. Detailed information was collected using a semistructured questionnaire on demographic, dietary, environmental, and occupational factors. Genotypes were determined by PCR-RFLP analysis. The XRCC3 codon 241 variant genotype exhibited a protective effect against bladder cancer [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.42-0.93], which was prominent among heavy smokers (OR, 0.49; 95% CI, 0.28-0.88) but not among never and light smokers. No overall impact of the XRCC1 codon 399 polymorphism was found (OR, 0.86; 95% CI, 0.59-1.28), but a protective influence of the homozygous variant was suggested among heavy smokers (OR, 0.38; 95% CI, 0.14-1.02). XPD polymorphisms did not show an association with bladder cancer (OR, 0.92; 95% CI, 0.62-1.37). There was no statistical evidence of an interaction between these three genetic polymorphisms and either tobacco smoking or occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines. The XRCC3 codon 241 polymorphism had an overall protective effect against bladder cancer that was most apparent among heavy smokers. Similarly, the XRCC1 codon 399 polymorphism also had a protective effect on bladder cancer among heavy smokers. The XPD polymorphism was not, however, associated with bladder cancer risk.

Adult↗

PubMedDate not supplied

[Analysis of DNA polymorphism of cluster genes in cattle: casein genes and major histocompatibility complex (MHC) genes].

The PCR-analysis method has been used to study polymorphism of casein genes (k- and b-caseins) and genes of class of basic histocompatibility complex (DRB and DQB BoLA) in some cattle breeds. Genotyping of k-casein locus has been carried out using analysis of protein polymorphism and DNA polymorphism. It is shown that both methods give identical results and can be used for this purpose, but the PCR-analysis method is more informative. A new allele of k-casein gene (k-Cn F) has been revealed and sequenced using the above method. While analyzing DNA-polymorphism of 5'-nontranslated region of b-casein gene two previously non-described polymorphic sites for restrictase Hinf I are found which occur only in animals of "zebu-like" breed. The high level of polymorphism of bl-domain of gene DRB is shown: polymorphism of bl-domain was revealed already at the level of electrophoretic analysis of PCR-amplification products. For 5'-nontranslated domain gene DQB the polymorphism level was much lower and manifested itself during restriction analysis of amplified fragments.

Amino Acid Sequence↗

PubMed2004

Polymorphisms of IL-1 beta gene in Japanese patients with Sjögren's syndrome and systemic lupus erythematosus.

OBJECTIVE: Interleukin (IL)-1 beta is a proinflammatory cytokine involved in various immune responses. Five polymorphisms in the IL-1 beta gene have been described, and relationships between these polymorphisms and some autoimmune diseases have been reported. Evidence suggests that IL-1 beta may be involved in the destruction of salivary and lacrimal glands in Sjögren's syndrome (SS). We evaluated the significance of IL-1 beta gene polymorphisms in SS. METHODS: Blood samples were taken from 101 patients with SS, 103 patients with systemic lupus erythematosus (SLE, excluding those with secondary SS), and 106 healthy volunteers. Each polymorphism of the IL-1 beta gene was analyzed by polymerase chain reaction (PCR) amplification of the polymorphic site, followed by site-specific restriction digestion. Genotype frequencies of each polymorphism in SS patients were compared with those of the controls and SLE patients, and differences between primary and secondary SS patients were also compared. RESULTS: Genotypes CC, TT, and AA in positions -511, -31, and 3877, respectively, were significantly less frequent in SS patients than controls or patients with SLE. No significant differences were found in genotype frequencies of any of the polymorphisms between patients with primary SS and secondary SS. CONCLUSION: IL-1 beta gene polymorphisms may affect susceptibility to SS, but not SLE.

DNA↗

PubMed2004

Genetic polymorphism of p53 and XRCC1 in cervical intraepithelial neoplasm in Taiwanese women.

BACKGROUND AND PURPOSE: Many epidemiological studies have investigated the relationship between p53 codon 72 polymorphism and cervical cancer risk, but the findings are still conflicting. In contrast, data are lacking on the relationship between XRCC1 polymorphism and cervical neoplasm risk. This community-based nested case-control study examined the association between genetic polymorphisms of p53 codon 72 and XRCC1 codons 194, 280, and 399 and cervical intraepithelial neoplasm (CIN) susceptibility in Taiwanese women. METHODS: Women living in Chiayi City, located in southwestern Taiwan, who had received Papanicolau (Pap) smear screening between October 1999 and December 2000 (n = 32,466) were included. Potential cases were women having lesions with cervical intraepithelial neoplasm II (CIN2) and over (> or = CIN2) reconfirmed by cervical biopsy. Potential controls (case:control = 1:2) were age matched (+/- 2 years) and residency matched women who had normal Pap smears. DNA samples were extracted from peripheral blood specimens and genetic polymorphisms of p53 and XRCC1 were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In total, 100 cases [97 high-grade squamous intraepithelial lesion (HSIL) and 3 invasive cancer] and 196 controls had complete demographic and clinical questionnaire data and data of analysis of XRCC1 polymorphism, whereas only 99 cases and 193 controls had complete data for p53 polymorphism. The frequency of pro/pro, pro/arg, and arg/arg in p53 codon 72 in cases was 15% (15/99), 58% (57/99), and 27% (27/99) and in controls was 17% (34/193), 48% (92/193), and 35% (67/193), respectively, which was not significantly different. The frequency of arg/arg, arg/gln, and gln/gln in XRCC1 codon 399 in cases was 54% (54/100), 38% (38/100), and 8% (8/100) and in controls was 58% (114/196), 37% (73/196), and 5% (9/196), respectively, which was not significantly different. No associations were found between XRCC1 codon 194 and 280 genotypes and HSIL risk. The joint effect of p53 and XRCC1 polymorphisms remained insignificant. CONCLUSIONS: Our data suggest that p53 codon 72 and XRRC1 codon 194, 280 and 399 genotypes do not influence CIN risk in the Taiwanese population.

Adult↗

PubMed2005

Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer.

Adenosine diphosphate ribosyl transferase (ADPRT) and X-ray repair cross-complementing 1 (XRCC1) are two major DNA base excision repair (BER) proteins and act interactively in stimulating and executing BER processes. Polymorphisms of ADPRT Val762Ala and XRCC1 Arg399Gln have been associated with altered protein function and BER activity. This case-control study examined the contribution of these two polymorphisms, alone and in combination, or in interaction with smoking, to the risk of developing lung cancer. We estimated the risk of lung cancer associated with these polymorphisms in 1,000 cases and 1,000 cancer-free controls using logistic regression models. Subjects having the ADPRT Ala/Ala genotype had an odds ratio (OR) of 1.68 [95% confidence interval (95% CI), 1.27-2.23] compared with those having the Val/Val genotype. A greater than multiplicative joint effect between the ADPRT polymorphism and smoking was observed. The ORs (95% CI) of the Ala/Ala genotype for nonsmokers and smokers who smoked < or =16, 16 to 28, or >28 pack-years were 1.13 (0.79-1.62), 1.35 (0.68-2.70), 2.46 (1.35-4.51) or 17.09 (8.15-35.83), respectively (P trend test < 0.001). Gene-gene interaction of ADPRT and XRCC1 polymorphisms increased risk of lung cancer in a supermultiplicative manner (OR for the presence of both ADPRT 762Ala/Ala and XRCC1 399Gln/Gln genotypes, 5.91; 95% CI, 2.09-16.72), although the XRCC1 polymorphism itself was not associated with the risk. In conclusion, the ADPRT Val762Ala polymorphism plays an important role in smoking-related lung cancer and the XRCC1 Arg399Gln polymorphism may serve as a risk modifier.

Aged↗

PubMed2005

Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival.

PURPOSE: The effects of estrogens are mediated primarily through estrogen receptor (ER) in breast tissue, and polymorphisms in the ER genes may alter the functions of these receptors. Polymorphisms in the ER-alpha gene have been reported to be associated with breast cancer risk. However, to our knowledge, no study has been published on the relation between ER-alpha gene polymorphisms and breast cancer survival. EXPERIMENTAL DESIGN: To determine whether three common polymorphisms in the ER-alpha gene, PvuII, XbaI, and GT dinucleotide repeats are associated with breast cancer survival, we evaluated data from a cohort of 1,069 breast cancer patients who participated in the Shanghai Breast Cancer Study between 1996 and 1998. The median follow-up time for this cohort of women was 5.2 years. RESULTS: No overall association was observed between ER gene polymorphisms and breast cancer survival. The genotype associations, however, were modified by ER status in breast cancer tissues. Comparing those with the PP genotype to the pp genotype of the PvuII polymorphism, the hazard ratios (HR) of dying were 3.30 [95% confidence interval (95% CI), 1.42-7.69] and 0.54 (95% CI, 0.24-1.23), respectively, for participants with ER-negative breast cancer and ER-positive breast cancer. Similarly, compared with those with no (GT)(23) alleles, carrying one or two (GT)(23) alleles of the GT repeat polymorphism was related to a HR of 1.48 (95% CI, 0.77-2.87) for ER-negative breast cancer and a HR of 0.25 (95% CI, 0.09-0.69) for ER-positive cancer. The effect of ER on breast cancer survival was also modified by genotypes of ER-alpha gene. Tests for multiplicative interaction were highly significant. CONCLUSIONS: These data suggest that the ER-alpha gene polymorphisms and ER status may have an interactive effect on breast cancer survival.

Adult↗