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Falcarindiol (FAD) is a natural polyyne have been found in many food and dietary plants. It has been found to have various beneficial biological activities. In this study, we demonstrated its anticancer function and mechanism in breast cancer cells. We found that FAD preferentially induces cell death in breast cancer cells. FAD-induced cell death is caspase-dependent. However, FAD induces autophagy to contribute to the cell death. Blocking autophagy by either chemical inhibitors or genetic knockout of autophagy signaling component inhibits FAD-induced cell death. We further found that FAD-induced cell death is mediated by the induction of endoplasmic reticulum stress. We also identified that FAD has synergistic effect with approved cancer drugs 5-FU and Bortezomib in killing breast cancer cells. Summarily, these data demonstrate that FAD has strong and specific anticancer effect in breast cancer cells, and provide some insights about the roles of autophagy in FAD-induced cell death. [ABSTRACT FROM AUTHOR]

Background: Phosphatase and tensin homolog (PTEN) is a well established tumor suppressor gene. Recently, increasing studies investigated the association between PTEN IVS4 polymorphism (rs3830675) and risk of various types of cancer. However, the results from the individual studies were controversial. The aim of this meta-analysis was to elucidate whether PTEN IVS4 polymorphism was associated with cancer risk. Methods: Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to assess the strength of association between PTEN IVS4 polymorphism and cancer risk. Results: A total of seven case-control studies were finally included in this meta-analysis. The pooled analysis suggested that individuals with PTEN IVS4 (−/−) genotype were significantly associated with increased risk of cancer (OR = 1.45, 95% CI = 1.19–1.76, P<0.001) and subgroup of digestive tract cancer (OR = 1.67, 95% CI = 1.28–2.18, P<0.001) compared with (+/+) genotype. The allele analysis revealed that (−) allele was significantly associated with increased risk of cancer (OR = 1.30, 95% CI = 1.12–1.50, P = 0.001) and subgroup of digestive tract cancer (OR = 1.42, 95% CI = 1.16–1.74, P = 0.001) compared with (+) allele. No significant association was observed between PTEN IVS4 (+/−) genotype and risk of cancer. Conclusion: PTEN IVS4 (−/−) genotype was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+/+) genotype. The (−) allele of PTEN IVS4 (rs3830675) polymorphism was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+) allele. The recessive effect model and dominant effect model also demonstrated significant association between PTEN IVS4 (rs3830675) polymorphism and increased cancer risk especially for digestive tract cancer. Further large-scale and well-designed studies regarding different ethnicities are still required to confirm the results of our meta-analysis. [ABSTRACT FROM AUTHOR]

Background: Variant in pri-miRNA could affect miRNA expression and mature process or splicing efficiency, thus altering the hereditary susceptibility and prognosis of cancer. We aimed to assess miRNA-let-7 single nucleotide polymorphisms (SNP) associated with the risk and prognosis of gastric cancer (GC) as predicting biomarkers, and furthermore, its possible mechanisms. Methods: A two-stage case-control study was designed to screen four miRNA SNPs (pri-let-7a-2 rs629367 and rs1143770, pri-let-7a-1 rs10739971, pri-let-7f-2 rs17276588) in 107 GC patients, 107 atrophic gastritis (AG), and matched 124 controls using PCR-RFLP. Two promising SNPs were validated in another independent 1949 samples (including 579 gastric cancer patients, 649 atrophic gastritis and 721 controls) using Sequenom MassARRAY platform and sequencing. Results: We found that pri-let-7a-2 rs629367 CC variant genotype was associated with increased risks of gastric cancer and atrophic gastritis by 1.83-fold and 1.86-fold, respectively. For gastric cancer prognosis, patients with rs629367 CC genotype had significantly poorer survival than patients with AA genotype (log-rank P = 0.004). We further investigated the let-7a expression levels in serum and found that let-7a expression elevated gradually for rs629367 AA, CA, CC genotype in the atrophic gastritis group (P = 0.043). Furthermore, we confirmed these findings in vitro study by overexpressing let-7a carrying pri-let-7a-2 wild-type A or polymorphic-type C allele (P<0.001). Conclusions: pri-let-7a-2 rs629367 CC genotype could increase the risks of gastric cancer as well as atrophic gastritis and was also associated with poor survival of gastric cancer, which possibly by affecting the mature let-7a expression, and could serve as a predicting biomarker for high-risk and poor prognosis of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence indicated that common polymorphisms of NOD2 might impact individual susceptibility to cancer. However, the results from published studies were inconclusive. The aim of this meta-analysis was to elucidate whether NOD2 polymorphisms were associated with cancer risk. Methods: A systematically literature search was performed by using electronic databases including PubMed and Web of Science. ORs and their 95% CI were used to assess the strength of association between NOD2 gene polymorphisms and cancer risks. Results: Thirty case-control studies were included in this meta-analysis. The pooled analysis indicated that NOD2 rs2066842 C/T polymorphism was not significantly associated with cancer risk; for NOD2 rs2066844 C/T polymorphism, (TT+CT) genotype was associated with increased cancer risk compared with wild-type CC genotype (OR = 1.32, 95% CI = 1.01–1.72, P = 0.041); for NOD2 rs2066845 C/G polymorphism, individuals with (CC+CG) genotype were significantly associated with increased cancer risk compared with GG genotype (OR = 1.32, 95% CI = 1.01–1.72, P = 0.040); for NOD2 rs2066847 (3020insC) polymorphism, carriers of (insC/insC+insC/−) genotype were significantly associated with increased cancer risk compared with −/− carriers (OR = 1.23, 95% CI = 1.10–1.38, P<0.001). In the subgroup analysis of cancer type, (insC/insC+insC/−) genotype was significantly associated with increased risk of colorectal cancer, gastric cancer and MALT lymphoma, breast cancer, lung cancer, laryngeal cancer but not with urogenital cancer, pancreatic cancer, melanoma or non-Hodgkin lymphoma. Conclusion: NOD2 rs2066844 C/T, rs2066845 C/G and rs2066847 (3020insC) polymorphisms might be associated with increased cancer risk. No significant association was observed between NOD2 rs2066842 C/T polymorphism and cancer risk. Further large-scale and well-designed studies are still needed to confirm the results of our meta-analysis. [ABSTRACT FROM AUTHOR]

Background: Phosphatase and tensin homolog (PTEN) is a well established tumor suppressor gene. Recently, increasing studies investigated the association between PTEN IVS4 polymorphism (rs3830675) and risk of various types of cancer. However, the results from the individual studies were controversial. The aim of this meta-analysis was to elucidate whether PTEN IVS4 polymorphism was associated with cancer risk., Methods: Databases including PubMed, Web of knowledge and Chinese National Knowledge Infrastructure (CNKI) were systematically searched to identify potentially eligible literatures. Odds ratios (OR) and their 95% confidence interval (CI) were used to assess the strength of association between PTEN IVS4 polymorphism and cancer risk., Results: A total of seven case-control studies were finally included in this meta-analysis. The pooled analysis suggested that individuals with PTEN IVS4 (-/-) genotype were significantly associated with increased risk of cancer (OR = 1.45, 95% CI = 1.19-1.76, P<0.001) and subgroup of digestive tract cancer (OR = 1.67, 95% CI = 1.28-2.18, P<0.001) compared with (+/+) genotype. The allele analysis revealed that (-) allele was significantly associated with increased risk of cancer (OR = 1.30, 95% CI = 1.12-1.50, P = 0.001) and subgroup of digestive tract cancer (OR = 1.42, 95% CI = 1.16-1.74, P = 0.001) compared with (+) allele. No significant association was observed between PTEN IVS4 (+/-) genotype and risk of cancer., Conclusion: PTEN IVS4 (-/-) genotype was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+/+) genotype. The (-) allele of PTEN IVS4 (rs3830675) polymorphism was significantly associated with increased risk of cancer especially for digestive tract cancer compared with (+) allele. The recessive effect model and dominant effect model also demonstrated significant association between PTEN IVS4 (rs3830675) polymorphism and increased cancer risk especially for digestive tract cancer. Further large-scale and well-designed studies regarding different ethnicities are still required to confirm the results of our meta-analysis.

Background: Emerging evidence indicated that common polymorphisms of NOD2 might impact individual susceptibility to cancer. However, the results from published studies were inconclusive. The aim of this meta-analysis was to elucidate whether NOD2 polymorphisms were associated with cancer risk., Methods: A systematically literature search was performed by using electronic databases including PubMed and Web of Science. ORs and their 95% CI were used to assess the strength of association between NOD2 gene polymorphisms and cancer risks., Results: Thirty case-control studies were included in this meta-analysis. The pooled analysis indicated that NOD2 rs2066842 C/T polymorphism was not significantly associated with cancer risk; for NOD2 rs2066844 C/T polymorphism, (TT+CT) genotype was associated with increased cancer risk compared with wild-type CC genotype (OR = 1.32, 95% CI = 1.01-1.72, P = 0.041); for NOD2 rs2066845 C/G polymorphism, individuals with (CC+CG) genotype were significantly associated with increased cancer risk compared with GG genotype (OR = 1.32, 95% CI = 1.01-1.72, P = 0.040); for NOD2 rs2066847 (3020insC) polymorphism, carriers of (insC/insC+insC/-) genotype were significantly associated with increased cancer risk compared with -/- carriers (OR = 1.23, 95% CI = 1.10-1.38, P<0.001). In the subgroup analysis of cancer type, (insC/insC+insC/-) genotype was significantly associated with increased risk of colorectal cancer, gastric cancer and MALT lymphoma, breast cancer, lung cancer, laryngeal cancer but not with urogenital cancer, pancreatic cancer, melanoma or non-Hodgkin lymphoma., Conclusion: NOD2 rs2066844 C/T, rs2066845 C/G and rs2066847 (3020insC) polymorphisms might be associated with increased cancer risk. No significant association was observed between NOD2 rs2066842 C/T polymorphism and cancer risk. Further large-scale and well-designed studies are still needed to confirm the results of our meta-analysis.