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ABSTRACT: Published data on the association between three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene and breast cancer risk are inconclusive. The aim of this human genome epidemiology review and meta-analysis was to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Web of science, and CBM databases from inception through July 2012 was conducted. Seventeen studies were included with a total of 21,742 breast cancer cases and 31,125 healthy controls. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of association in allele model, dominant model, recessive model, homozygous model, and heterozygous model. When all the eligible studies were pooled into the meta-analysis, remarkable associations between the rs11200014 (A>G) polymorphism and breast cancer risk were detected in Caucasians (G vs. A: OR = 1.28, 95 % CI: 1.21-1.35; GG/AG vs. AA: OR = 1.32, 95 % CI: 1.18-1.48), but not in Asians and Africans. In addition, there were statistically significant associations between the rs2981579 (G>A) polymorphism and increased risk of breast cancer risk in all ethnicities (A vs. G: OR = 1.20, 95 % CI: 1.11-1.29; AA/GA vs. GG: OR = 1.32, 95 % CI: 1.18-1.48; AA vs. GG: OR = 1.67, 95 % CI: 1.55-1.81), including Caucasians, Asians, and Africans. However, the TT genotype of rs2981578 (C>T) polymorphism might decrease breast cancer risk (TT vs. CC/CT: OR = 0.55, 95 % CI: 0.38-0.79; TT vs. CC: OR = 0.51, 95 % CI: 0.35-0.76; TT vs. CT: OR = 0.58, 95 % CI: 0.40-0.85), especially among Asians. Results from the current meta-analysis indicates that three novel functional polymorphisms (rs11200014, rs2981579, and rs2981578) in the promoter of FGFR2 gene are associated with breast cancer susceptibility and might be a potential biomarkers for breast cancer risk.
Breast Cancer Research and Treatment 11/2012; · 4.43 Impact Factor
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ABSTRACT: Emerging evidence from preclinical and clinical studies has shown that interleukin-12 (IL-12) has some effectiveness against endogenously arising carcinogenesis. Several potentially functional polymorphisms of IL-12 gene have been implicated in cancer risk, but individually published studies showed inconclusive results. The aim of this study was to investigate the association between IL-12 polymorphisms and cancer risk.
The MEDLINE, EMBASE, Web of science and CBM databases were searched for all articles published up to June 10, 2012 that addressed IL-12 polymorphisms and cancer risk. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 softwares.
Eighteen studies were included with a total of 6463 cancer cases and 7412 healthy controls. We found that the 3'UTR A>C (rs3212227) polymorphism of IL-12B gene was associated with significantly increased overall risk of cancers using random effects model (C vs A: odds ratio [OR]=1.14, 95% confidence interval [CI]: 1.02-1.27; AC+CC vs AA: OR=1.20, 95%CI: 1.01-1.43). However, the 3'UTR G>A (rs568408), IVS2 T>A (rs582054) and 5'UTR T>G (rs2243115) polymorphisms of IL-12A gene did not appear to have an influence on cancer susceptibility. Further subgroup analyses showed that the 3'UTR A>C (rs3212227) polymorphism was associated with increased cancer risks in the subgroups of Asians, cervical and nasopharyngeal cancers.
Results from the current meta-analysis indicates that the 3'UTR A>C (rs3212227) polymorphism of IL-12B gene might be a potential biomarker for cancer risk among Asians, especially for cervical and nasopharyngeal cancers.
Gene 08/2012; 510(1):71-7. · 2.34 Impact Factor
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ABSTRACT: Sinomenine (SIN) is a bioactive component derived from a Chinese medicinal plant. Our previous studies demonstrated that SIN has cytotoxic effects on human lung cancer cells. However, the antitumor molecular mechanisms of SIN have yet to be elucidated in detail. In the present study, we further explored the effects of SIN on NCI-H460 human lung cancer cell viability and apoptosis and investigated the regulation and function of PI3K/Akt and ERK signaling pathways during SIN-induced apoptosis in various lung cancer cell lines. NCI-H460 cells were incubated with 200 µg/ml SIN for the indicated times (0, 24, 48 or 72 h). Cell viability was assessed by MTT assay. Akt, p-Akt, ERK1/2 and p-ERK1/2 protein levels were detected by western blotting, respectively. Two different selective inhibitors (LY294002 for the PI3K pathway; PD98059 for the MEK/ERK pathway) were used to characterize the relative roles of PI3K/Akt and ERK in SIN-induced apoptosis. Apoptosis was determined by flow cytometry. SIN inhibited the proliferation of NCI-H460 cells in a time-dependent manner, which was accompanied with significant activation of pAkt and pERK. LY294002 and PD98059 both significantly increased SIN-induced apoptosis in NCI-H460, NCI-H226 and NCI-H522 cells. Our findings suggest that the activation of the PI3K/Akt and ERK signaling pathways antagonize SIN-induced lung cancer cell apoptosis and molecules that inhibit these pathways should potentiate the effects of SIN. This study represents a significant step forward in our understanding of the signal transduction pathways associated with the apoptosis elicited by SIN.
Molecular Medicine Reports 02/2012; 5(5):1256-60. · 0.42 Impact Factor
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ABSTRACT: Adriamycin (ADM) is a drug used in the treatment of various types of cancer and exerts an antineoplastic effect mainly through the induction of apoptosis. Phosphoinositide 3 kinase (PI3K)/Akt and MAPK are fundamental survival pathways activated by exposure to most chemotherapeutical agents. However, the role of these pathways in the ADM-induced apoptosis of leukemia cells remains unclear. In the present study, ADM triggered dose-dependent cytotoxicity and resulted in a significant loss of cell viability in HL-60 cells. Moreover, treatment with ADM significantly reduced mitochondrial membrane potential (ΔΨm) in the cells. Akt and ERK activation was also detected, and the inhibition of these two pathways resulted in the enhancement of ADM-induced apoptosis. These results indicate that the PI3K/Akt and ERK survival pathways antagonize the chemotherapeutic effect of ADM. Thus, inhibiting these pathways may serve to enhance the effect of ADM.
Molecular Medicine Reports 3(4):641-4. · 0.42 Impact Factor
