Association of genetic polymorphisms in MIF with breast cancer risk in Chinese women

Macrophage migration inhibitory factor (MIF) has been reported to associate with increased cancer risk in several cancers. However, the role of MIF in breast cancer (BC) susceptibility remains unknown. For the first time, we conducted a case–control study to assess the potential association of three common MIF gene variants (rs755622, rs1803976, rs11548059) with BC susceptibility in Chinese women. Total 560 breast cancer patients and 583 age- and sex-matched healthy individuals were recruited from Northwest China, and the DNA was genotyped by Sequenom MassARRAY. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed to estimate the associations. We found that C/G, C/C, and C/G–C/C genotype carriers in MIF rs755622 have a significantly increased risk of BC (C/G vs. G/G: OR = 1.36, 95% CI = 1.07–1.75, P = 0.014; C/C vs. GG: OR = 2.01, 95% CI = 1.06–3.79, P = 0.029; C/G–C/C vs. G/G: OR = 1.42 95% CI = 1.11–1.80, P = 0.004). Further analyses indicate that the BC risk is associated with Ki-67 status, and the rs755622 polymorphism increases breast cancer risk among elder patients (≥49 years). There is no association between BC risk and other two polymorphisms (rs1803976 and rs11548059) by overall analysis and stratified analysis. In conclusion, MIF rs755622 polymorphism increases BC susceptibility in Chinese population, especially among elder patients.     

Associations between PTPN2 polymorphisms and susceptibility to ulcerative colitis and Crohn’s disease: a meta-analysis

Objective

Ulcerative colitis (UC) and Crohn’s disease (CD) result from an interaction between genetic and environmental factors. Though several polymorphisms have been identified in PTPN2, their roles in the incidence of UC and CD are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk.

Method

PubMed, EMBASE, Cochrane Library and CBM were searched until 23 July 2013 for eligible studies on three PTPN2 polymorphisms: rs2542151, rs1893217 and rs7234029. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 % CIs) were calculated.

Conclusion

The meta-analysis indicated that rs2542151, rs1893217 and rs1893217 were associated with increased CD risk, while the former was associated with increased UC risk. The differences in age of onset and ethnic groups may influence the associations. Gene–gene and gene–environment interactions should be investigated in the future.

Results

Seventeen studies with 18,308 cases and 20,406 controls were included. Significant associations were found between rs2542151 polymorphism and CD susceptibility (OR = 1.22, 95 % CI, 1.15–1.30, I ² = 32 %), as well as between rs2542151 and UC susceptibility (OR = 1.16, 95 % CI, 1.07–1.25, I ² = 39 %). A similar result was found in Caucasians, but not in Asians. Moreover, a significant increase in CD risk for all carriers of the minor allele of rs1893217 (OR = 1.45, 95 % CI, 1.23–1.70, I ² = 0 %) and rs7234029 (OR = 1.36, 95 % CI, 1.16–1.59, I ² = 0 %) were found. For children, the rs1893217 polymorphism appeared to confer susceptibility to CD (OR = 1.56, 95 % CI, 1.28–1.89, I ² = 0 %).     

Evaluate the relationship between polymorphisms of OAS1 gene and susceptibility to chronic hepatitis C with high resolution melting analysis

The aim of this was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the OAS1 gene and the susceptibility to chronic hepatitis C virus (HCV) infection in a population from the Liaoning Province of China. High resolution melt (HRM)-PCR analysis was conducted to examine three OAS1 SNPs: rs2660 G/A, rs10774671 G/A, and rs3741981 G/A in 298 chronic HCV-infected patients and in 305 healthy controls and to identify a relationship between SNP genotype and susceptibility to chronic HCV infection using a case–control study design. These three OAS1 SNPs were in strong linkage disequilibrium (rs2660 vs. rs10774671: |D’|=1.000, r ² =1.000; rs2660/rs10774671 vs. rs3741981: |D’|=0.938, r ² =0.569). The frequency of AG + GG genotypes in both rs2660 and rs10774671 and the AA + AG genotype in rs3741981 was significantly higher among chronic HCV-infected patients than among control (P < 0.001); the A allele in all three SNPs was found more frequently in the chronic HCV-infected group than in the control group (rs2660 and rs10774671: P = 0.02; rs3741981: P < 0.001). Moreover, individuals carrying the A allele in these SNPs exhibited an increased risk for chronic HCV infection (rs2660 and rs10774671: OR = 1.356 [1.051–1.749]; rs3741981: 1.363 [1.085–1.712]). The haplotype created by the G allele at both rs2660 and rs10774671 and the A allele at rs3741981 increased the risk of chronic HCV infection by 3.394-fold (95 % CI 1.406–8.201). Our results identify OAS1 SNP rs2660, rs10774671, and rs3741981 as genetic risk factors for chronic HCV infection. Polymorphisms of the OAS1 gene might affect the susceptibility to chronic infection with HCV.     

The Impact of HLA-G 3′UTR Polymorphisms in Breast Cancer in a Tunisian Population

Human leukocyte antigens G and E (HLA-G and HLA-E) are nonclassical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting natural killer and cytotoxic T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases including tumor. The main objective of the study is to evaluate the impact of three HLA-G 3?UTR potential polymorphisms: +3187 A > G (rs9380142), +3142 G > C (rs1063320), +2960 14-base pair (bp) Insertion/Deletion (Ins/Del) (rs66554220), and the HLA-E*01:01/01:03 A > G (rs1264457) polymorphism in Tunisian breast cancer population. A total of 355 patients and 381 controls were genotyping for HLA-G and HLA-E polymorphisms using a Taq Man assay. +3142 C allele and +3142 C/C genotype were significantly associated with increased risk of breast cancer (p = 0.00002; OR = 1.58; 95% CI = 27–1.97) (49% versus 35%; p = 0.0001; OR = 1.79; 95% CI = 1.32–2.44). In addition, Del allele and the homozygous state for Del/Del genotype confer a risk for breast cancer (52% versus 45%, p = 0.006; OR = 1.33, 95% CI = 1.08–1.64) (28% versus 22%, p = 0.039; OR = 1.43, 95% CI = 0.90–2.25). However, no statistical significant differences were reported for HLA-G + 3187 A > G and HLA-E variations and breast cancer in a Tunisian population.

The found results indicate that HLA-G may play an important role in the breast cancer.     

Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11–4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25–3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).     

New single nucleotide polymorphisms (SNPs) in homologous recombination repair genes detected by microarray analysis in Polish breast cancer patients

Breast cancer is the most common cause of malignancy and mortality in women worldwide. This study aimed at localising homologous recombination repair (HR) genes and their chromosomal loci and correlating their nucleotide variants with susceptibility to breast cancer. In this study, authors analysed the association between single nucleotide polymorphisms (SNPs) in homologous recombination repair genes and the incidence of breast cancer in the population of Polish women. Blood samples from 94 breast cancer patients were analysed as test group. Individuals were recruited into the study at the Department of Oncological Surgery and Breast Diseases of the Institute of the Polish Mother’s Memorial Hospital in Lodz, Poland. Healthy controls (n = 500) were obtained from the Biobank Laboratory, Department of Molecular Biophysics, University of Lodz. Then, DNA of breast cancer patients was compared with one of the disease-free women. The test was supported by microarray analysis. Statistically significant correlations were identified between breast cancer and 3 not described previously SNPs of homologous recombination repair genes BRCA1 and BRCA2: rs59004709, rs4986852 and rs1799950. Further studies on larger groups are warranted to support the hypothesis of correlation between the abovementioned genetic variants and breast cancer risk.     

Genetic variants of TLR4 and TLR9 are risk factors for chronic Helicobacter pylori infection in South Indian Tamils

Toll like receptors (TLRs) are a class of molecular pattern recognition receptors, elicits a strong inflammatory immune response against pathogens. Helicobacter pylori (H. pylori), a gram negative flagellate colonizes the human stomach, is responsible for the development of chronic gastritis and gastric carcinoma. The higher incidence of H. pylori infection and gastric cancer in South Indian Tamils demands a genetic study to unravel the influence of TLR4 and TLR9 polymorphisms associated with chronic H. pylori infection. In this study, 230 healthy individuals and 77 patients diagnosed with H. pylori infection were screened for TLR4 (rs1927914, rs4986790, rs4986791) and TLR9 (rs352140, rs34399053, rs150459369) polymorphisms by PCR-RFLP and ARMS-PCR. We observed that the individuals harboring heterozygous and homozygous polymorphic variants of TLR4 conferred a significant risk to develop chronic H. pylori infection and peptic ulcer disease [rs4986790 AG, p = 0.001, OR-2.7, 95%CI: 1.5–5.03; GG, p = 0.0006, OR-9.8, 95%CI: 2.4–39.4; rs4986791CT, p = 0.0001, OR-7.2, 95%CI: 3.7–7.2; TT, p = 0.0001, OR-7.9, 95%CI: 2.6–23.7]. Also, the heterozygous variant of TLR9 rs352140, favoured the persistence of the H. pylori infection [p = 0.037, OR-1.87, 95%CI: 1.07–3.29]. Thus our findings suggest that TLR4 rs4986790, rs4986791 and TLR9 rs352140 polymorphisms are potential genetic risk factors influencing the disease susceptibility and clinical manifestation of chronic H. pylori infection in Indian Tamils.     

Analysis of LINGO1 (rs9652490) polymorphism in sporadic Parkinson's disease in a Polish population,and a meta-analysis

Recently, a variant in LINGO1 (also denominated as LRRN6A) rs9652490:A>G gene has been found to associate with increased risk of essential tremor (ET). Because ET and Parkinson's disease (PD) may be ethiologically related, we proceeded to conduct an analysis of the SNP in PD population. In the current study LINGO1 rs9652490:A>G polymorphism was evaluated in a cohort of 162 Polish patients diagnosed with PD and 177 controls by means of MALDI-TOF mass spectrometry. Any significant differences in rs9652490 genotype or allele frequencies between the studied groups were noted. Our findings demonstrate that LINGO1 SNP (rs9652490) is not associated with sporadic PD in our Polish cohort. A meta-analysis of the available data suggests protective role of rs9652490GG genotype (OR 0.70, 95% CI: 0.51–0.96, p = 0.028).     

The clinicopathological evaluation of the breast cancer patients with brain metastases: predictors of survival

We aimed to define the clinicopathologic characteristics of breast cancer (BC) patients with brain metastasis (BM) and to investigate the effect of these parameters on survival. Seventy-nine patients diagnosed with BC and symptomatic BM between 1995 and 2011 were retrospectively evaluated. The relationship between clinicopathological features and outcome was investigated. Triple negative patients had the shortest overall survival (OS) while HR(+)HER2(?) patients had the longest (48.2  vs 88.2 months, 95 % CI; p = 0.33). Multivariate analysis demonstrated that luminal A subtype was the strongest positive predictor of prolonged OS (HR 0.48, 95 % CI 0.28–0.84; p = 0.01), while poor performance status (PS) (ECOG 3–4) at BM was the strongest predictor of shortened OS (HR 1.92, 95 % CI 1.21–3.06; p = 0.006). The patients with early-stage BC at diagnosis had BM later than the advanced-staged patients (47 months for Stage I–II disease, 23.2 months for Stage III–IV disease, 95 % CI; p = 0.002). Median survival after BM was 10.2 months (6.4–14 months, 95 % CI). The patients with liver or skin metastases had significantly shorter survival than the patients with only BM (4.8 vs 17 months, p < 0.001 for liver and 4.8 vs 11.1 months, p = 0.04 for skin). Multivariate analysis demonstrated that regardless of the BC subtype, lack of systemic therapy, and liver involvement were independent factors associated with increased risk of death (HR 4, 95 % CI 1.7–9.1; p = 0.001 and HR 2.2, 95 % CI 1.05–4.9; p = 0.036 respectively). Clinical outcome after BM mostly depends on the ECOG PS and the fact that whether the patient received systemic therapy or not. Systemic therapy prolongs survival especially in HER2 positive patients.     

ERAP1-ERAP2 haplotypes are associated with ankylosing spondylitis in Polish patients

The objective of this case-control study was to evaluate the role of four single-nucleotide polymorphisms in the ERAP1 (rs2287987, rs30187, rs27044) and ERAP2 (rs2248374) genes and their haplotypes in predicting the risk for ankylosing spondylitis (AS) on a well-defined Polish population. Our study confirmed the strong association between the HLA-B*27 allele and the disease. For all tested ERAP1 SNPs we found significant differences in the minor allele and genotype distribution between patients and controls. The strongest association with AS was observed for rs30187. The minor T allele and homozygous TT genotype of this SNP significantly increased disease risk (OR = 1.56, 95%CI = 1.22–1.99, p = 0.0004 and OR = 2.52, 95%CI = 1.50–4.25, p = 0.001, respectively). In the case of rs2287987, minor C allele exerted a protective effect (OR = 0.64, 95%CI = 0.46–0.88, p = 0.008). In contrast to ERAP1, we observed no effect of rs2248374 in ERAP2 on the disease. We also carried out ERAP1-ERAP2 haplotype analysis to demonstrate a possible association of both genes with AS. Results showed that the haplotype H4, containing ERAP1 SNPs associated with high enzymatic activity, together with the presence of ERAP2 expression, significantly increased the risk of AS (OR = 1.97, 95% CI = 1.21–3.21, p_corr = 0.048). By contrast, the haplotype H5 coding for low activity of ERAP1 and the lack of ERAP2 expression was strongly protective (OR = 0.41, 95% CI = 0.23–0.72, p_corr = 0.008).     

NLRP3 gene is associated with ulcerative colitis (UC), but not Crohn’s disease (CD), in Chinese Han population

Objective

This study aimed to investigate whether NLRP3 is associated with IBD in Chinese Han population.

Methods

Three SNPs were genotyped using polymerase chain reaction with sequence-specific primers in 288 patients [232 Crohn’s disease (CD) patients, 56 ulcerative colitis (UC) patients] and 274 controls.

Results

In IBD group, the results showed no significant association. When subdivided to CD and UC, it showed in CD subgroup, there was no significant association. However, in UC subgroup, rs10754558 (P _allele = 0.015272, P _genotype = 0.029776, OR [95 % CI] = 0.604190[0.401200–0.909886]) and rs10925019 (P _allele = 0.013042, P _genotype = 0.037045, OR [95 % CI] = 2.022613[1.149854–3.557812]) have significant associations with UC. The G and T alleles were risk factors of the susceptibility of UC, the GG and TT genotypes may increase risk of this disease. Rs4925648 has no association with UC. The haplotypes analysis results showed as follow: for rs4925648–rs10925019, CC and TT are risk factors for UC (for CC, χ ² = 3.605, P = 0.057613, OR [95 % CI] = 1.645 [0.980–2.761], for TT, χ ² = 5.522, P = 0.018804, OR [95 % CI] = 0.426[0.205–0.884]), and for rs10754558–rs10925019, CT and GC haplotypes are risk factors for UC (for CT, χ ² = 3.545, P = 0.059739, OR [95 % CI] = 0.571[0.317–1.029], for GC, χ ² = 9.359, P = 0.002228, OR [95 % CI] = 1.904 [1.255–2.887]).

Conclusions

We first demonstrated that rs10754558 and rs10925019 are significantly associated with the susceptibility of UC, but not CD in Chinese Han population, suggesting that NLRP3 may play an important role in the pathogenesis of UC.     

The association between interleukin-1β gene polymorphisms and the risk of breast cancer: a systematic review and meta-analysis

IntroductionIt is reported that there is a close association between interleukin-1β (IL-1β) gene polymorphisms and breast cancer risk. However, the results remain controversial.Material and methodsEligible published articles were searched in PubMed, Embase, and Web of Science databases up to June 2018. Odds ratios with 95% confidence intervals were used to identify potential links between IL-1β genetic polymorphisms and the risk of breast cancer.ResultsFrom our results, we found that three common polymorphisms in IL-1β (rs16944, rs1143634, rs1143627) had no significant associations with breast cancer risk in all genetic models. Based on the analysis from ethnic subgroups, there was a higher risk of breast cancer for rs16944 polymorphism in the recessive model and heterozygous model among Asians (TT vs. CC+CT: 1.229, 95% CI: 1.063–1.422, p = 0.005; TT vs. CT: 1.211, 95% CI: 1.057–1.388, p = 0.006). For the rs1143627 polymorphism, a significantly decreased breast cancer risk was observed in the dominant model only in Asians (CT+TT vs. CC: OR = 0.944, 95% CI: 0.897–0.994, p = 0.027). After stratifying patients according to the menopausal state, we found that polymorphism of rs1143627 correlated with reduced breast cancer risk among post-menopausal women in three genotype models: allele, recessive model and homozygous model (T vs C: 0.859, 95% CI: 0.753–0.98, p = 0.024; TT vs. CC+CT: 0.727, 95% CI: 0.576–0.918, p = 0.007; TT vs. CC: 0.743, 95% CI: 0.626–0.882, p = 0.001). As for other analyses with reference to source of controls and genotyping methods, no significant association between IL-1β polymorphism and breast cancer risk was demonstrated.ConclusionsThe rs16944 and rs1143627 polymorphisms are significantly associated with the risk of breast cancer only in Asian people and in post-menopausal women respectively.     

Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer

Objectives: The aims of this study are to (1) study the influence of polymorphisms in adiponectin gene on adiponectin levels and potential associations with breast, prostate and colon cancer; (2) investigate the associations of adiponectin levels with other adipokines and breast, prostate and colon cancers. Subjects: We measured fasting adiponectin, leptin, insulin, Sex steroids in 132 (66 females, 66 males) cancer patients and 68 age and sex matched apparently healthy subjects. Body Mass Index (BMI) and waist circumference were used as indices of obesity. Insulin Resistance was assessed using Homeostasis Model Assessment (HOMA). Three single nucleotide polymorphisms (SNP rs182052 (G-10066-A), SNP rs1501299 (276G > T), SNP rs224176 (45T > G) in adiponectin gene were studied using Real Time Polymerase Chain Reaction. Results: GG genotype of SNP rs1501299 was significantly associated with higher levels of adiponectin (OR=1.2, 95%CI(1.03–1.3), p = 0.02); breast (OR=8.6, 95%CI(1.03–71), p = 0.04), colon cancers (OR= 12, 95%CI(1.2–115), p = 0.03). GT genotype was also associated significantly with colon cancer (OR=2.6, 95%CI (1.1–6), p = 0.03). However SNP rs224176 was associated with only breast cancer. Conclusion: Our results demonstrate that adiponectin gene SNP rs1501299 and SNP rs224176 may be the predisposing factors in some cancers but our results differ from what has been reported in other populations suggesting a complex relationship between genetic variations and phenotypic adiponectin levels.     

The effects of <Emphasis Type="Italic">SP110</Emphasis>’s associated genes on fresh cavitary pulmonary tuberculosis in Han Chinese population

SP110 is a promising anti-Mycobacterium tuberculosis (MTB) gene. To investigate the effects of SP110 and its associated genes, i.e., MYBBP1A and RELA, on pathological progression of MTB infection, an association study with 424 patients of fresh pulmonary tuberculosis (PTB) and 424 healthy controls was performed. Moreover, classification and regression tree and multifactor dimensionality reduction were employed to explore the effects of gene–gene interactions on cavitary PTB. The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 had significant effects on the risk of PTB (OR 1.42, 95 % CI 1.06–1.92, p 0.019; OR 1.55, 95 % CI 1.04–2.33, p = 0.033, respectively), and heterozygous genotype CT in rs9061 also had similar effects (OR 1.43, 95 % CI 1.07–1.90, p = 0.014). The rs3809849 and rs9905742 in MYBBP1A were also significantly associated with cavitary PTB (p = 0.00046 and 0.039, respectively), while rs9061 in SP110 had no such association (p = 0.06931) except its significant association with non-cavitary PTB (p = 0.0093). The interaction of MYBBP1A and RELA had significant effect on cavitary PTB (OR 4.24, 95 % CI 1.44–12.49, p = 0.005). These suggest that MYBBP1A instead of SP110 may be a genetic risk factor for cavitary PTB and play important effects on its whole progress.     

Genetic Variation at the TPH2 Gene Influences Impulsivity in Addition to Eating Disorders

Genes are involved in eating disorders (EDs) and self-induced vomiting (SV), a key symptom of different types of EDs. Perfectionism and impulsivity are potential risk factors for EDs. TPH2 (tryptophan hydroxylase 2) SNP rs1473473 was previously associated with anorexia nervosa and EDs characterized by SV. Could perfectionism or impulsivity be underlying the association between rs1473473 and EDs? Genetic association between TPH2 SNP rs1473473 and perfectionism or impulsivity was first evaluated in a random control group (N = 512). The associations obtained in this control group were subsequently tested in a group of patients with an ED (N = 267). The minor allele of rs1473473 (OR = 1.49) was more frequent in impulsive controls, but also in impulsive patients with an ED (OR = 1.83). The largest effect was found in the patients with an ED characterized by SV (OR = 2.51, p = 0.02). Genetic variation at the TPH2 gene appeared to affect impulsivity which, in turn, might predispose to the SV phenotype.     

Interleukin-28B TT genotype is frequently found in patients with hepatitis C virus cirrhosis but does not influence hepatocarcinogenesis

Persistent hepatitis C virus (HCV) infection is associated with progressive hepatic fibrosis and ultimately hepatocellular carcinoma. The interleukin-28B (IL28B) rs12979860 polymorphism is associated with fibrosis progression in chronic HCV infection. IL28B encodes interferon-λ, which has both antiviral and anti-proliferative properties. This study aimed to determine whether IL28B rs12979860 polymorphism is also associated with development of hepatocellular carcinoma both in chronic HCV infection and in non-viral-related cirrhosis. Real-time polymerase chain reaction and melting curve analyses were used to genotype 311 patients who underwent liver transplantation for HCV cirrhosis (n = 202) or alcoholic cirrhosis (n = 109). HCV patients were older (p = 0.012) and less likely males (p < 0.001) than patients with alcoholic cirrhosis. IL28B rs12979860 TT genotype [OR 6.08, 95 % CI 2.11–17.53; p < 0.001] and T allele carriage (CT + TT; OR 2.3, CI 95 % 1.42–3.72; p = 0.001) were more frequent among HCV patients and, among them, more common in patients infected with HCV genotype 1 (CT + TT; OR 1.79, CI 95 % 1.03–3.09; p = 0.009). Incidence of hepatocellular carcinoma was higher in HCV cirrhosis (OR 2.7, CI 95 % 1.5–4.7; p < 0.001), with no differences according to HCV genotype. IL28B genotype distribution was similar among patients with or without hepatocellular carcinoma, in both HCV patients regardless viral genotype (p = 0.84) and alcoholic patients (p = 0.91). Multivariate analysis showed that older age (OR 1.06, CI 95 % 1.02–1.1; p = 0.003) and male gender (OR 2.49, CI 95 % 1.24–5; p = 0.01) were independent risk factors for hepatocellular carcinoma in HCV patients. In summary, the current study did not find a significant association between IL28B rs12979860 polymorphism and hepatocarcinogenesis.     

CXCL12, CXCR4 and IFNγ genes expression: implications for proinflammatory microenvironment of breast cancer

Signals from the microenvironment have a profound influence on the maintenance or progression of breast cancer. In the present study, the frequency of CXCL12 rs1801157 polymorphism in peripheral blood and the expression of CXCL12, CXCR4 and IFNγ mRNA in normal and mammary gland tumor tissues were assessed in breast cancer patients. Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism and expression analyses by quantitative RT-PCR. A lower CXCL12 mRNA relative expression was observed among allele A carriers when compared to GG carriers (p = 0.012). ER-positive breast cancer allele A carriers showed a significantly lower expression of CXCL12 mRNA within tumor tissue than in normal breast tissue when compared to GG ER-positive patients (p = 0.016). CXCR4 mRNA (p < 0.001) and CXCL12 mRNA (p = 0.02) relative expressions were significantly correlated with relative IFNγ mRNA expression. Allele A carriers presenting high levels of IFNγ had a significantly higher expression of CXCR4 mRNA in tumor tissue than GG patients (p = 0.026). It is possible that allele A carrier hormone receptor–positive patients could be more susceptible to metastasis development, since they present a lower CXCL12 expression in tumor tissue, and tumor cells expressing CXCR4 could migrate toward CXCL12 gradient. IFNγ expression increases in order to improve immune response and could favor higher CXCR4 expression leading to migration of cells, possibly of metastatic ones, too.     

Association of overexpression of hexokinase II with chemoresistance in epithelial ovarian cancer

This aim of this study was to evaluate the relationship between hexokinase II expression and chemoresistance in epithelial ovarian cancer. One hundred and eleven paraffin-embedded specimens from patients with epithelial ovarian cancer were immunohistochemically stained for hexokinase II. Subsequently, the association between hexokinase II overexpression and clinicopathologic characteristics including chemoresistance was assessed. Survival analyses were also performed for evaluating the prognostic value of hexokinase II overexpression. Tumor recurrence within 6 months after termination of first-line chemotherapy was considered to indicate chemoresistance. Hexokinase II overexpression was associated with chemoresistance (p = 0.029) and was an independent risk factor for chemoresistance [odds ratio (OR) 3.37; 95 % confidence interval (CI) 1.07–10.62; p = 0.038] along with non-optimal debulking surgery (OR 4.93; 95 % CI 1.43–16.98; p = 0.011). Hexokinase II overexpression was significantly associated with decreased progression-free survival (p = 0.002) and showed a similar trend for overall survival (p = 0.101). Cox regression analysis revealed that hexokinase II overexpression was an independent prognostic factor for early recurrence (hazard ratio 2.63; 95 % CI 1.40–4.92; p = 0.002). Our findings suggest that hexokinase II overexpression is associated with short progression-free survival, which could be associated with chemoresistance in epithelial ovarian cancer.