African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer

Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR) = 2.34, 95% confidence interval (CI) 1.23–4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P = 0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR = 3.00, 95%CI 1.29–6.99). Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases.     

Monocyte chemoattractant protein-1 (MCP-1) gene polymorphism as a potential risk factor for cardiovascular disease in hemodialyzed patients

Aim: Polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene (A-2518G) has been associated with functional effects. The aim of the present study was to assess the effect of this polymorphism on end-stage renal disease (ESRD) and cardiovascular disease (CVD) in hemodialyzed patients. Methods: A total of 720 patients with ESRD treated with hemodialysis (450 patients with CVD) and 325 healthy control subjects were genotyped for the MCP-1 -2518 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. Results: There was a significant difference in genotype frequencies between entire group of hemodialyzed patients and controls (p < 0.01). The odds ratio for the risk allele was 1.85, 95% CI 1.49–2.32 (p < 0.01). Hemodialyzed patients were divided into subgroups with CVD (n = 450) and without CVD (n = 270). The G allele carriers occurred with significantly higher frequency in patients with CVD (62% vs. 38% in patients without CVD and 36% in controls). The odds ratio for the risk allele for patients with CVD vs. those without CVD was 2.17, 95% CI 1.71–2.79. There was no statistically significant difference in the distribution of MCP-1 genotypes between ESRD patients without CVD and healthy controls. Conclusion: Our results demonstrate for the first time an association between the polymorphism in the regulatory region of the MCP-1 gene and susceptibility to CVD in hemodialyzed patients.     

Associations between glutathione S-transferase π Ile105Val and glyoxylate aminotransferase Pro11Leu and Ile340Met polymorphisms and early-onset oxaliplatin-induced neuropathy

Purpose: Although the risk of oxaliplatin-induced neuropathy depends on cumulative oxaliplatin dose, susceptibility to this adverse event differs greatly among patients. In this study, we investigated the associations between oxaliplatin-induced neuropathy and the following polymorphisms: glutathione S-transferase π (GSTP1) Ile¹⁰⁵Val, and glyoxylate aminotransferase (AGXT) Pro¹¹Leu and AGXT Ile³⁴⁰Met. Experimental design: Eighty-two Japanese patients with histologically confirmed colorectal cancer who received at least six cycles of the modified FOLFOX6 (m-FOLFOX6) regimen were enrolled. To minimize differences in cumulative oxaliplatin dose between patients, oxaliplatin-induced neuropathy was evaluated using an oxaliplatin-specific scale during the 2-week period after completion of the sixth cycle of treatment. Results: Forty-four patients developed grade 2/3 oxaliplatin-induced neuropathy. There were more patients carrying at least one GSTP1¹⁰⁵Val allele among the group with grade 2/3 neuropathy (18/44, 41%) than among the group with grade 1 neuropathy (9/38, 24%), although the difference was not statistically significant (P = 0.098). There were similar numbers of patients carrying at least one AGXT¹⁰⁵Met allele in the grade 2/3 neuropathy (7/44, 16%) and grade 1 neuropathy groups (5/38, 13%; P = 0.725). The AGXT¹¹Leu allele was not found in any of our patients or controls. Conclusions: We found no significant association between oxaliplatin-induced neuropathy and the GSTP1 Ile¹⁰⁵Val and AGXT Ile³⁴⁰Met polymorphisms. Given that no AGXT¹¹Leu allele was found among our study population (n = 177), evaluating this polymorphism in Japanese patients in future studies is likely to be uninformative.     

Association between interleukin 15 receptor, alpha (IL15RA) polymorphism and Korean patients with ossification of the posterior longitudinal ligament

ObjectivesRecently, a number of evidences have been reported concerning the genetic factor involved in the development of ossification of the posterior longitudinal ligament (OPLL). The purpose of this study was to investigate single nucleotide polymorphisms (SNPs) of the interleukin 15 receptor, alpha (IL15RA) gene as a risk factor in Korean patients with OPLL.DesignTo investigate the genetic association, two coding SNPs (rs2296139, Thr73Thr; rs2228059, Asn182Thr) in IL15RA were genotyped in 166 OPLL patients and 230 control subjects. SNPStats, SNPAnalyzer, and Helixtree programs were used for association analysis.ResultsIn the present study, we found the association between a missense SNP (rs2228059) and the risk of OPLL in codominant (p = 0.0028, OR = 1.58, 95% CI = 1.17–2.14), dominant (p = 0.0071, OR = 1.82, 95% CI = 1.17–2.82), and recessive models (p = 0.036, OR = 1.79, 95% CI = 1.04–3.09). The frequency of rs2228059 allele was significantly associated with the susceptibility of OPLL (p = 0.0043, OR = 1.52, 95% CI = 1.14–2.02). After Bonferroni correction, the missense SNP (rs2228059, Asn182Thr) still had significant correlations (p = 0.0056 in codominant model; p = 0.0142 in dominant model; p = 0.0086 in allele analysis). Haplotype variation in IL15RA was associated with OPLL (global haplotype test, p = 0.025).ConclusionsThese results suggest that IL15RA polymorphism may be associated with the susceptibility of OPLL in Korean population.     

Effect of G(-174)C polymorphism in interleukin-6 gene on cardiovascular disease in type 2 diabetes patients

Interleukin-6 (IL-6) is an important pro-inflammatory cytokine of relevance to cardiovascular diseases. The aim of this case-control study was to evaluate the association between the G(-174)C functional polymorphism in the IL-6 gene and risk of cardiovascular disease (CVD) in type 2 diabetes patients. We examined 1090 patients with T2DM and 612 controls. All subjects were genotyped for the G(-174)C polymorphism by polymerase chain reaction (PCR) and restriction analysis. There were no significant differences in the distribution of genotypes and alleles between T2DM patients and healthy controls. Significantly higher C allele frequency was observed in CVD+ patients compared to CVD- subgroup (53% vs. 32%, p < 0.0001). The odds ratio for C allele was 2.4 (95% CI 1.99–2.9, p < 0.0001) and for CC genotype 4.55 (95% CI 3.12–6.63, p < 0.000). When the distribution of G(-174)C polymorphism was compared in subgroups with different clinical phenotypes of CVD, a significant association of CC genotype with myocardial infarction was observed. Forty eight percent of patients with MI had the CC genotype compared to 22% of patients without MI (p < 0.0001). In conclusion, type 2 diabetes patients carrying the C allele of the IL-6 G(-174)C polymorphism have a significantly increased risk of CVD.     

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR) = 1.48, 95% CI: 1.14–1.91, P < 0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR = 1.70, 95% CI: 1.28–2.27, P < 0.01). However, differences in SCE frequency were not observed (FR = 1.14, 95% CI: 0.81–1.61, P > 0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR = 1.35, 95% CI: 1.02–1.80, P < 0.05); age, older workers exhibited higher MN frequencies than younger workers (FR = 1.45, 95% CI: 1.14–1.84, P < 0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR = 1.40, 95% CI: 1.10–1.77, P < 0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (?) (FR = 1.48, 95% CI: 1.14–1.92) or GSTT1 (?) (FR = 1.42, 95% CI: 1.10–1.83) genotypes, and especially those who carried both (FR = 2.10, 95% CI: 1.43–3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P > 0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.     

Association of Interleukin 6 gene polymorphisms with genetic susceptibilities to spastic tetraplegia in males: A case-control study

BackgroundCerebral palsy (CP) is a group of non-progressive motor impairment and permanent disorders causing limitation of activity and abnormal posture. It may be caused by infection (such as chorioamnionitis), asphyxia or multiple genetic factors. The Interleukin 6 gene (IL6) was suggested to be involved in the susceptibilities to CP risk as a kind of proinflammatory cytokine.ObjectiveTo explore the genetic association between the polymorphisms of the IL6 gene and CP in the Chinese population.MethodsA total of 542 CP patients and 483 healthy control children were recruited in this study to detect five single nucleotide polymorphisms (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL6 locus. Genotyping of SNPs was performed by the MassArray platform-based genotyping approach. The SHEsis program was applied to analyze the genotyping data.ResultsOf the five selected SNPs, no significant allelic and genotypic association was found between CP patients and controls. However, subgroup analysis found significant differences in allele frequencies between spastic tetraplegia in males compared with controls at rs1800796 (OR = 1.39, P = 0.033, P = 0.099 after SNPSpD correction) and rs2069837 (OR = 1.58, P = 0.012, P = 0.035 after SNPSpD correction). The frequencies of the C allele of rs1800796 and the A allele of rs2069837 were greater in males with spastic tetraplegia than in the controls. The two SNPs haplotype rs1800796 (G) – rs2069837 (G) were also associated with a decreased risk of spastic tetraplegia in males (OR = 0.619, P = 0.009, P = 0.027 after Bonferroni correction).ConclusionGenetic variation of the IL6 gene may influence susceptibility to spastic tetraplegia in males and its role in cerebral palsy deserves further evaluation in a large-scale and well-designed study.     

Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population

Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with myocardial infarction (MI) have been reported. This study investigated the relationship of the −786T>C (rs2070744), 894G>T (rs1799983) and 4a4b polymorphisms of the NOS3 gene with the presence of MI in the Tunisian population. In addition, we also examined the association of NOS3 gene haplotypes with MI in Tunisian subjects.A total of 303 patients with MI and 225 controls were included in the study. The 894G>T and −786T>C single nucleotide polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR.There was significant linkage disequilibrium between the three NOS3 polymorphisms (p < 0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not −786T>C and 894G>T, polymorphism was significantly different between MI patients and controls. The univariate logistic regression analysis showed a significant association of the 4a4b polymorphism and MI according to co-dominant, dominant and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24–15.41; p = 0.021, dominant model OR: 1.66, 95%CI: 1.14–2.42); p = 0.007, and recessive model OR: 3.85, 95%CI: 1.10–13.47; p = 0.035). The multivariate analysis, adjusted for traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was an independent predisposing factor to MI, according to the models considered. In addition, a haplotype 7 (C-T-4a), (OR = 12.05, p = 0.010) was a risk factor of MI after controlling for classical risk factors.These finding suggest that the 4a4b polymorphism of the NOS3 gene was associated with MI in Tunisian patients.     

Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)

PurposeThough polymorphisms of the tumor suppressor gene p53 have been extensively investigated in numerous tumors, particularly tumors associated with human papillomavirus (HPV) infection. However, the results remain controversial. Our previous study showed that HPV serostatus is not an independent risk factor for esophageal squamous cell carcinoma (ESCC) in nonsmokers and nondrinkers. Given the roles of p53 and HPV E6 as well as MDM2 oncoproteins in p53 degradation, we validated the association of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.MethodsSingle nucleotide polymorphisms of p53 Arg72Pro (rs1042522) and MDM2 (rs937283) in 307 ESCC patients and 311 healthy controls were genotyped. The presence or absence of HPV16 in serum was measured by enzyme-linked immunosorbent assay. Multivariable logistic regression analysis was used to evaluate the possible associations of p53 and MDM2 polymorphisms with ESCC risk stratified by HPV16 sero-status.ResultsPatients carrying p53 Arg/Arg or Arg/Pro had a higher risk of esophageal SCC (P < 0.001, Odds ratio [OR] 4.98, 95% confidential interval [CI] 3.46–7.17), however, not found in MDM2 rs937283. The risk of esophageal SCC increased significantly among patients carrying p53 Arg/Arg, or Arg/Pro and HPV16-seropositivity (P < 0.001, OR 9.33, 95% CI 5.44–16.0), but not for MDM2 rs937283. The risk of esophageal SCC was further elevated among patients carrying Arg/Arg or Arg/Pro and HPV16-seropositivity who were smokers (P < 0.001, OR 27.05, 95% CI 11.06–66.16) or drinkers (P < 0.001, OR 13.20, 95% CI 5.74–30.38).ConclusionHPV16 seropositivity synergized with p53 Arg/Arg or Arg/Pro and increased ESCC risk, especially in smokers or drinkers.     

The polymorphism and haplotype of TLR3 gene in grass carp (Ctenopharyngodon idella) and their associations with susceptibility/resistance to grass carp reovirus

Toll-like receptors (TLRs) have emerged as crucial sensors of invading microbes through recognition of pathogen-associated molecular patterns (PAMPs) in viruses, bacteria, fungi and protozoa. The polymorphisms in TLRs are closely associated with the resistance to pathogen infections. TLR3 involved in the recognition of double stranded RNA in humans, mice, pigs and fishes. In present study, the nucleotide sequence polymorphisms of TLR3 gene in grass carp (Ctenopharyngodon idella) (CiTLR3) were investigated to explore their association with susceptibility/resistance to grass carp reovirus (GCRV). Twelve single nucleotide polymorphisms (SNPs) and an ins/del mutation were detected in the complete sequence of CiTLR3. Ten of them were sited in the non-coding region. The two SNPs in exon were synonymous mutation. The ins/del mutation was coincidental at the start codon. To investigate the association between the polymorphism and the susceptibility/resistance to GCRV, we selected eight SNPs in the non-coding region and analyzed the genotype and allele distribution in susceptible and resistant groups with PCR-RFLP. The statistical results indicated that only ?764 G/T was significantly associated with the resistance of grass carp to GCRV both in genotype (P = 0.040) and allele (P = 0.025). Linkage disequilibrium analysis revealed ?543 A/G, ?488 G/T, 4116 G/T and 4731 C/T were linkage disequilibrium, and haplotype analysis revealed that haplotype GTTT frequency in susceptible group was significantly higher than that in the resistant group (OR = 2.01, 95% CI 0.996–4.043, P = 0.049). To further confirm the correlation, an additional infection experiment was carried out. The mortality in the ?764 GG genotype individuals was significantly lower than GT genotype (OR = 0.208, 95% CI 0.067–0.643, P = 0.011) and TT genotype (OR = 0.183, 95% CI 0.052–0.648, P = 0.015). All the results indicated that haplotype GTTT and genotype ?764 TT and ?764 GT individuals were susceptible to GCRV while ?764 GG was resistant, which could be the optional markers for selective breeding for the GCRV-resistant grass carp in future.     

Interleukin-1 receptor antagonist gene (IL1RN) polymorphism possibly associated to severity of rheumatic carditis in a Brazilian cohort

Aims: To evaluate the IL1RN polymorphism as a possible marker for Rheumatic Fever (RF) susceptibility or disease severity. Methods: The genotypes of 84 RF patients (Jones criteria) and 84 normal race-matched controls were determined through the analysis of the number of 86-bp tandem repeats in the second intron of IL1RN. The DNA was extracted from peripheral-blood leukocytes and amplified with specific primers. Clinical manifestations of RF were obtained through a standardized questionnaire and an extensive chart review. Carditis was defined as new onset cardiac murmur that was perceived by a trained physician with corresponding valvae regurgitation or stenosis on echocardiogram. Carditis was classified as severe in the presence of congestive heart failure or upon the indication for cardiac surgery. The statistical association among the genotypes, RF and its clinical variations was determined. Results: The presence of allele 1 and the genotype A1/A1 were found less frequently among patients with severe carditis when compared to patients without this manifestation (OR = 0.11, p = 0.031; OR = 0.092, p = 0.017). Neither allele 1 nor allele 2 were associated with the presence of RF (p = 0.188 and p = 0.106), overall carditis (p = 0.578 and p = 0.767), polyarthritis (p = 0.343 and p = 0.313) and chorea (p = 0.654 and p = 0.633). Conclusion: In the Brazilian population, the polymorphism of the IL-1ra gene is a relevant factor for rheumatic heart disease severity.     

Association between the IFNG +874A/T gene polymorphism and leprosy resistance: A meta-analysis

Previous studies identified the variant IFNG +874A/T (rs2430561) in the first intron of the gene in association with mycobacterial infection, especially tuberculosis and leprosy. The aim of this investigation was to analyze the protective role of the T allele in relation to leprosy using a meta-analysis evaluation. Thus, 1573 patients and 1914 controls were included and analyzed in fixed effects model. The T allele is associated with a protective effect for leprosy under the dominant model (pooled OR = 0.83, 95% CI = 0.72–0.96, p = 0.011) suggesting that carriers of the IFNG +874T allele may be protected from developing leprosy. The T allele has been suggested to correlate with high interferon-γ levels. A phenotype with high IFN-γ producing and an increased inflammatory profile may account for these findings. This meta-analysis suggests that IFNG +874T allele is associated with leprosy resistance.     

Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren’s syndrome

Introduction: Macrophage migration inhibitory factor (MIF) has been shown to be a key regulator in innate and adaptive immune responses. A single nucleotide polymorphism in the 5′ region of the MIF gene, MIF -1731G/C, is associated with increased MIF protein production, in vivo and in vitro. Associations have been shown between the minor MIF -173C allele and sarcoidosis patients with erythema nodosum (EN). Löfgren’s syndrome is an acute and usually self-remitting phenotype of sarcoidosis. It is defined as having an acute onset with bilateral hilar lymphadenopathy (BHL), fever, erythema nodosum (EN) and/or arthritis.The aim of this study was to investigate whether MIF -173G/C associates with the susceptibility to and the clinical manifestations, i.e. arthritis or EN, of Löfgren’s syndrome.A total of 171 patients with Löfgren’s syndrome and 313 controls were genotyped for a single nucleotide polymorphism at position -173 of the MIF gene (SNP rs755622), using a PCR and a restriction enzyme technique.Results: There were no significant differences found in the MIF -173C allele frequencies between patients with Löfgren’s syndrome and controls. In patients with Löfgren’s syndrome with only EN, a significantly increased frequency of the C minor allele was observed compared to patients with arthritis only (p = 0.0095; OR 3.08, CI: 1.28–7.39).Patients with only EN compared to patients with EN and arthritis showed a significantly increased frequency of the minor C allele (p = 0.044; OR 1.97, CI: 1.01–3.85). But patients with only arthritis compared to patients with EN and arthritis did not show a significant difference in C allele frequency (p = 0.270; OR 0.64, CI: 0.29–1.42).Conclusions: The MIF -173C allele is associated with erythema nodosum in Löfgren’s syndrome, but not with susceptibility to sarcoidosis. This indicates a role for MIF after antigen presenting to the T cell has taken place and the sarcoid inflammatory response has begun.     

Polymorphisms of IL-10 gene in patients infected with HCV under antiviral treatment in southern Brazil

Interleukin-10 (IL-10) is a cytokine that plays an important role in the regulation of the immune system. Gene polymorphisms of IL-10 have been associated with the different expression levels of this cytokine. In hepatitis C virus infection, IL-10 appears to interfere with the progression of disease, viral persistence and the response to therapy. This study investigated genetic variability in the IL-10 gene promoter between patients infected with hepatitis C virus (HCV) and healthy individuals, associating the frequency of polymorphisms with different aspects of viral infection. This is a case-control study with 260 patients who were infected with HCV and 260 healthy individuals. Genotyping of the polymorphisms was performed using the technique of amplification refractory mutation system PCR (ARMS-PCR) for regions of the IL-10 gene promoter (-1082 G/A, -819 C/T, -592 C/A). The frequencies of alleles and genotypes related to polymorphisms in the IL-10 gene promoter showed a higher frequency of the G allele and genotype GG in the -1082 region between the infected group and the control group (p = 0.005 and p = 0.001, respectively), whereas the AA genotype was significantly more frequent in the control group. The frequencies of the haplotypes GTA and GCC were higher in the group of infected individuals, whereas the haplotype ATA was more frequent in the healthy group (p < 0.006). It was also observed that the genotypes GG and AG in the region -1082 were significantly more frequent among patients infected with HCV who were in advanced stages of fibrosis and cirrhosis (p = 0.042). No association was observed between polymorphisms of IL-10 and sustained virologic response (SVR).     

Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer

In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n = 46) and immunohistochemistry (n = 213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p = 0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n = 17) or breast benign lesions (n = 16) (p = 0.014). Interestingly, siRNA-mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p = 0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p = 0.0023), relapse-free survival (p = 0.0013), and metastasis-free interval (p = 0.006) in patients with primary ER-negative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression.     

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

Background: Catechol-estrogen metabolites can induce carcinogenesis by acting as endogenous tumor initiators. Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is a main metabolic pathway of estrogen detoxification in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphisms and prostate cancer risk. Patients and methods: 129 patients with prostate cancer and 260 healthy controls were included in our study. A(TA)TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. Results: No significant differences were observed between the cancer group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P > 0.05). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA(7) vs TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.18). In addition, no association was revealed between UGT1A1 genotype distribution and Gleason score (P = 0.55). Conclusion: Our data suggest that the TA repeat polymorphism of UGT1A1 gene does not seem to alter prostate cancer risk susceptibility in Caucasian men.     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.