• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9699-9706
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• 2014

Background: The predictive value of the xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism regarding clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, but the results remain inconclusive. Therefore, we performed a meta-analysis to determine the precise role of the XPD Lys751Gln polymorphism in this clinical situation and optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs), generalized odds ratio (ORG) and their 95% confidence intervals (CIs) were used to estimate the objective response, while hazard ratios (HRs) with 95%CIs were used for progression-free survival (PFS) and overall survival (OS). Results: A total of 17 studies including 2,286 patients met the inclusion criteria. Overall, the XPD 751Gln allele was associated with a non-significant reduced objective response to oxaliplatin-based chemotherapy in all patients or in the Asian and Caucasian subgroups. However, poor PFS and OS of CRC patients treated with oxaliplatin-based regimens were significantly related to the XPD 751Gln allele in the dominant model (PFS: HR=2.10, 95%CI: 1.65-2.67; OS: HR=3.18, 95%CI: 1.57-6.47). On stratified analysis by ethnicity, these relationships were more pronounced in Asians (PFS: HR=2.49, 95%CI: 1.79-3.47; OS: HR=5.25, 95%CI: 3.46-7.94) than in Caucasians (PFS: HR=1.73, 95%CI: 1.22-2.46; OS: HR=1.78, 95%CI: 1.06-2.99). Conclusions: The XPD Lys751Gln polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6385-6390
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• 2012

A number of studies have been conducted to explore the association of XRCC1 polymorphisms with thyroid cancer risk, but the results have been inconsistent. Thus we performed the present meta-analysis to clarify this issue based on all of the evidence available to date. Relevant studies were retrieved by searching PubMed and statistical analysis conducted using Stata software. Nine studies were included in this meta-analysis (1,620 cases and 3,557 controls). There were 6 studies (932 cases and 2,270 controls) of the Arg194Trp polymorphism, 7 studies (1432 cases and 3356 controls) of the Arg280His polymorphism and 9 studies (1,620 cases and 3,557 controls) for the Arg399Gln polymorphism. No association of XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism with thyroid cancer risk was observed in the overall analysis. However, subgroup analysis revealed: 1) an elevated risk in aa vs AA analysis (OR=2.03, 95%CI= 1.24-3.31) and recessive genetic model analysis (OR=1.93, 95%CI= 1.20-3.08) in the larger sample size trials for XRCC1 Arg194Trp polymorphism; 2) a decreased thyroid cancer risk on subgroup analysis based on ethnicity in Aa vs AA analysis (OR=0.84, 95%CI= 0.72-0.98) and in a dominant genetic model (OR=0.84, 95%CI= 0.72-0.97) in Caucasian populations for the XRCC1 Arg399Gln polymorphism; 3) a decreased thyroid cancer risk on subgroup analysis based on design type in Aa vs AA analysis (OR=0.72, 95% CI= 0.54-0.97) among the PCC trials for the Arg399Gln polymorphism. Our results suggest that the XRCC1 Arg399Gln polymorphism may be associated with decreased thyroid cancer risk among Caucasians and XRCC1 Arg194Trp may be associated with a tendency for increased thyroid cancer risk in the two larger sample size trials.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5761-5767
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• 2013

The potential correlation of X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism with hepatocellular carcinoma (HCC) susceptibility is ambiguous. Taking account of inconsistent results of previous meta-analyses and new emerging literatures, we conducted a meta-analysis covering 15 case-control datasets to evaluate the relationship. Relevant studies from Medline, Embase and CNKI were retrieved. A fixed-effect model or a random-effect model, depending on between-study heterogeneity, were applied to estimate the association between XRCC1 polymorphism Arg399Gln and HCC risk with the results presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). In accordance with Hardy-Weinberg equilibrium, 15 studies with data for 6,556 individuals were enrolled in this systematic review. For overall HCC,thr XRCC1 polymorphism Arg399Gln was significantly associated with HCC susceptibility in a homozygote model as well as in a dominant model (G/G vs. A/A, OR=1.253, p=0.028; G/G+A/G vs. A/A, OR= 1.281, p=0.047, respectively), but not in a heterozygote model (A/G vs. A/A, OR=1.271, p=0.066) or a recessive model (G/G vs. A/G + A/A, OR= 1.049, p=0.542). Similar results were also observed on stratification analysis by ethnicity (A/G vs. A/A, OR=1.357, p=0.025; G/G vs. A/A, OR=1.310, p=0.011; G/G+A/G vs. A/A, OR= 1.371, p=0.013). However, no potential contribution of XRCC1 Arg399Gln polymorphism to HCC susceptibility in HBV/HCV subgroups was identified. No publication bias was found in this study. In conclusion, the XRCC1 Arg399Gln polymorphism contributes to HCC susceptibility. Due to the lack of studies in Western countries, further large-sample and rigorous studies are needed to validate the findings.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4413-4416
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• 2012

Aim: Individual differences in chemosensitivity and clinical outcome in non-small cell lung cancer (NSCLC) patients treatment with platinum-based chemotherapy may be due to genetic factors. Our study aimed to investigate the prognostic role of GSTP1, XRCC1 and XRCC3 in NSCLC patients treated with chemotherapy. Methods: A total of 460 cases were consecutively selected from The Affiliated Hospital of Nantong University between Jan. 2003 to Nov. 2006, and all were followed-up until Nov. 2011. Genotyping of GSTP1 Ile105Val, XRCC1 Arg194Trp, XRCC1 Arg399Gln and XRCC3 Thr241Met was conducted by duplex polymerase-chain-reaction with confronting-two-pair primer methods. Results: Patients with GSTP Val/Val exhibited a shorter survival time, and had a 1.89 fold greater risk of death than did those with the IIe/IIe genotype. For XRCC1 Arg194Trp, the variant genotype Trp/Trp was significantly associated with a decreased risk of death from NSCLC when compared with the Arg/Arg. Individuals carrying XRCC1 399Gln/Gln genotype had a longer survival time, with a lowered risk of death from NSCLC. Conclusion: This study indicated that GSTP1 Ile105Val, XRCC1 Arg194Trp and XRCC1Arg399Gln genes have a role in modifying the effect of platinum-based chemotherapy for NSCLC patients in a Chinese population. Our findings provide information for therapeutic decisions for individualized therapy in NSCLC cases.

• Molecules and Cells
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• v.28 no.3
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• pp.167-174
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• 2009

Genistein has been reported to potentiate glucose-stimulated insulin secretion (GSIS). Inhibitory activity on tyrosine kinase or activation of protein kinase A (PKA) was shown to play a role in the genistein-induced potentiation effect on GSIS. The aim of the present study was to elucidate the mechanism of genistein-induced potentiation of insulin secretion. Genistein augmented insulin secretion in INS-1 cells stimulated by various energygenerating nutrients such as glucose, pyruvate, or leucine/glutamine (Leu/Gln), but not the secretion stimulated by depolarizing agents such as KCl and tolbutamide, or $Ca^{2+}$ channel opener Bay K8644. Genistein at a concentration of $50{\mu}M$ showed a maximum potentiation effect on Leu/Gln-stimulated insulin secretion, but this was not sufficient to inhibit the activity of tyrosine kinase. Inhibitor studies as well as immunoblotting analysis demonstrated that activation of PKA was little involved in genistein-induced potentiation of Leu/Gln-stimulated insulin secretion. On the other hand, all the inhibitors of $Ca^{2+}$/calmodulin kinase II tested, significantly diminished genistein-induced potentiation. Genistein also elevated the levels of $[Ca^{2+}]_i$ and phospho-CaMK II. Furthermore, genistein augmented Leu/Gln-stimulated insulin secretion in CaMK II-overexpressing INS-1 cells. These data suggest that the activation of CaMK II played a role in genistein-induced potentiation of insulin secretion.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.449-452
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• 2013

Polymorphisms in DNA repair genes have been shown to influence DNA repair processes and to modify cancer susceptibility. Here we conducted a case-control study to assess the role of potential SNPs of DNA repair genes on the risk of glioma and meningioma. We included 297 cases and 458 cancer-free controls. Genotyping of XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC2 Arg188His, XRCC3 Thr241Met, XRCC4 Ala247Ser, ERCC1 Asn118Asp, ERCC2 Lys751Gln and ERCC5 Asp1558His were performed in a 384-well plate format on the Sequenom MassARRAY platform. XRCC1 Arg194Trp (rs1799782) and ERCC2 Asp312Asn rs1799793 did not follow the HWE in control group, and genotype distributions of XRCC1 Gln399Arg rs25487, XRCC2 Arg188His rs3218536 and ERCC2 Asp312Asn rs1799793 were significantly different between cases and controls (P<0.05). We found XRCC1 399G/G, XRCC1 194 T/T and XRCC3 241T/T were associated with a higher risk when compared with the wild-type genotype. For ERCC5 Asp1558His, we found G/G genotype was associated with elevated susceptibility. In conclusion, our study has shown that XRCC1 Gln399Arg, XRCC1 Arg194Trp, XRCC3 Thr241Met and ERCC5 Asp1558His are associated with risk of gliomas and meningiomas. This finding could be useful in identifying the susceptibility genes for these cancers.

• Korean Journal of Microbiology
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• v.40 no.4
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• pp.355-358
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• 2004

Chunkookjang, Korean traditional fermented soybean food emerges as a functional food to improve intestinal function and blood circulation. During Chungkookjang fermentation, microorganisms, enzymes, and diverse bioactive compounds increase sharply. Chungkookjang contains diverse oligo-peptides. Formation of peptides was confirmed by SDS-PAGE. Solube fermented soybean in our sample contained Tyr, Gln-Lys, Trp, Gln, and Lys-Pro as major components. Lys-Pro (0.083 mg/100 g sample) was purified by HPLC analysis. Angiotensin I­converting enzyme (ACE) causes hypertension by converting angiotensin I to angiotension II. ACE inhibitory activity of Lys-Pro was determined to be $IC_{50}=32.1\;{\mu}M.$ Whether or not eating Chungkookjang can lower blood pressure was also determined. Sistolic blood pressure dropped by 15 mmHg, and diastolic blood pressure by 8 mmHg 2 hr after a single administration of 20 g of fermented soybean. Chungkookjang might be helpful in improving blood circulation since it has ACE inhibitor and antihypertenisve effect.

• Journal of Genetic Medicine
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• v.4 no.2
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• pp.160-166
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• 2007

Purpose : The ${\beta}$-adrenoceptors are pharmacologically classified into ${\beta}_1$-, ${\beta}_2$- and ${\beta}_3$-adrenoceptor. The gene of each subtype has polymorphisms related to their function (${\beta}_1$-adrenoceptor: Ser49Gly, ${\beta}_2$-adrenoceptor: Gln27Glu, ${\beta}_3$-adrenoceptor: Trp64Arg). The objectives of this study were to analyse the allelic and genotypic distribution of the representative polymorphism of ${\beta}$-adrenoceptors in preeclampsia and to investigate whether combined genotype of ${\beta}$-adrenoceptors may be associated with preeclampsia. Methods : Blood samples were collected from a Korean population (159 preeclamptic pregnancies and 168 normotensive pregnancies). The ${\beta}_1$-, ${\beta}_2$- and ${\beta}_3$-adrenoceptor genotypes was determined using polymerase chain reaction-restriction fragment length polymorphism. Results : There were no differences in allelic and genotypic distribution of ${\beta}_1$- and ${\beta}_2$-adrenoceptor polymorphisms between the two groups. However, the Arg allele of ${\beta}_3$-adrenoceptor polymorphism were more frequent in preecalmpsia than in controls (P<0.05, OR=1.57, 95% CI=1.01-2.46). Moreover, prevalence of genotype carrying heterozygote of ${\beta}_3$-adrenoceptor polymorphism was increased in preeclampsia compared with controls (P<0.05, OR 1.76, 95% CI 1.06-2.92). When combination of the three polymorphisms were evaluated, pregnancies with the particular combined genotype that is consisted of heterozygote of ${\beta}_1$-, ${\beta}_3$-adrenoceptor and wild homozygote of ${\beta}_2$-adrenoceptor (Ser/Gly, Gln/Gln, Trp/Arg), showed a significant increase in the risk of preeclampsia (P<0.05, OR=3.01, 95% CI 1.12-8.08). Conclusion : A particular combined genotype (Ser/Gly, Gln/Gln, Trp/Arg) of - adrenoceptors was associated with the risk of preeclampsia.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1133-1140
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• 2014

Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (${\geq}24kg/m^2$). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< $24kg/m^2$). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ${\geq}2$ adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2811-2819
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• 2016

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.