Association between insulin-like growth factor 1 gene rs35767 polymorphisms and cancer risk: A meta-analysis.
ABSTRACT: BACKGROUND:Several studies have been conducted on the relationship between insulin-like growth factor 1 gene (IGF-1) rs35767 polymorphisms and cancer risk, but the results are conflicting. We performed a meta-analysis to investigate the relationship between IGF-1 rs35767 polymorphisms and cancer risk. METHODS:Eight studies (5 for IGF-1 rs35767 C>T and 3 for IGF-1 rs35767 A>G) with a total of 11,257 cases and 16,213 controls were included. The studies were about the association between IGF-1 rs35767 polymorphisms and cancer risk and acquired by searching PubMed, Embase, and Web of Science databases for articles published before January 20, 2019. STATA software was used to analyze the data and identify the strength of the association by using pooled-odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS:No significant associations were observed between the IGF-1 rs35767 C>T polymorphism and cancer risk in all genetic models. However, the IGF-1 rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR?=?1.087, 95% CI: 1.036-1.141, Ph?=?.338; GG vs AA: OR?=?1.272, 95% CI: 1.121-1.442, Ph?=?.359; AG vs AA: OR?=?1.187, 95% CI: 1.043-1.351, Ph?=?.695; AG+GG vs AA: OR?=?1.187, 95% CI: 1.043-1.351, Ph?=?.695; GG vs AA+AG: OR?=?1.086, 95% CI: 1.025-1.151, Ph?=?.275). Begg and Egger tests showed that no publication bias existed. CONCLUSION:Our findings indicated that the IGF-1 rs35767 A>G polymorphism might be a risk factor for cancer development. However, additional well-designed studies with sample sizes larger than ours need to be conducted in the future to verify our findings.
Project description:The study was performed to investigate the genetic associations of IGF-1 polymorphisms rs35767, rs5742714, and rs972936 with susceptibility to osteonecrosis of the femoral head (ONFH) among Chinese Han population.Totally, 101 ONFH patients and 128 healthy controls were enrolled. Hardy-Weinberg equilibrium (HWE) was detected with chi-square test in control group. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to estimate the relationship between IGF-1 polymorphisms and ONFH risk. Besides, hyplotype analysis was performed to examine linkage disequilibrium between the studied polymorphisms.Genotype AA and allele A of polymorphism rs35767 were more frequent in control group, and offered protection for ONFH onset (AA: OR?=?0.382, 95% CI?=?0.158-0.923; A: OR?=?0.650, 95% CI?=?0.442-0.956). Furthermore, the negative relationship was also observed between ONFH risk and polymorphism rs5742714 under the comparisons CG vs CC, and G vs C (OR?=?0.395, 95%CI?=?0.199-0.787; OR?=?0.346, 95%CI?=?0.191-0.627). While the polymorphism rs972936 significantly enhanced the disease risk (CT vs CC: OR?=?2.434, 95% CI?=?1.184-5.003; TT vs CC: OR?=?2.497, 95% CI?=?1.040-5.990). Furthermore, haplotype analysis demonstrated that C-T (rs5742714-rs972936) could increase ONFH risk (OR?=?2.177, 95% CI?=?1.444-3.283), while G-T might be a protective factor for ONFH (OR?=?0.472, 95% CI?=?0.254-0.878).IGF-1 polymorphisms rs35767, rs5742714, and rs972936 show significant association with ONFH risk.
Project description:BACKGROUND:A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance. METHODOLOGY/PRINCIPAL FINDINGS:Two samples of adult nondiabetic white Europeans were studied. In sample 1 (n=569), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (190±77 vs. 218±97 ng/ml, respectively; P=0.007 after adjusting for age, gender, and BMI). Insulin sensitivity assessed by euglycaemic-hyperinsulinemic clamp was lower in GG genotype carriers compared with A allele carriers (8.9±4.1 vs. 10.1±5.1 mg x Kg(-1) free fat mass x min(-1), respectively; P=0.03 after adjusting for age, gender, and BMI). The rs35767 polymorphism did not show significant association with insulin clearance. In sample 2 (n=859), IGF-1 levels were lower in GG genotype carriers compared with A allele carriers (155±60 vs. 164±63 ng/ml, respectively; P=0.02 after adjusting for age, gender, and BMI). Insulin sensitivity, as estimated by the HOMA index, was lower in GG genotype carriers compared with A allele carriers (2.8±2.2 vs. 2.5±1.3, respectively; P=0.03 after adjusting for age, gender, and BMI). CONCLUSION/SIGNIFICANCE:The rs35767 polymorphism near IGF1 was associated with circulating IGF-1 levels, and insulin sensitivity with carriers of the GG genotype exhibiting lower IGF-1 concentrations and insulin sensitivity as compared with subjects carrying the A allele.
Project description:Osteoporosis is a systemic metabolic and serious skeletal disease commonly observed among the elderly. Insulin-like growth factors (IGFs) are critical regulators for bone cell function. We estimated the role of IGF-I rs35767, rs2288377 and rs5742612 polymorphisms in the susceptibility to osteoporosis in a population of China, and assessed gene-environment interactions. A total of 346 patients with osteoporosis and 346 controls were enrolled. Genotyping of IGF-I rs35767, rs2288377 and rs5742612 was amplified and performed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The TA and AA genotypes displayed elevated risk of developing osteoporosis (TA vs TT: OR=1.54, 95% CI=1.11-2.15; AA vs TT: OR=3.65, 95% CI=2.09-6.37). Compared with TT individuals, individuals with the TA+AA genotype had a substantial increased susceptibility to osteoporosis (OR=1.80, 95% CI=1.31-2.46). In recessive model, the AA genotype of rs2288377 displayed 2.89 folds risk of osteoporosis (adjusted OR=2.89, 95% CI=1.70-4.89). A significant negative interaction was found between IGF-I rs2288377 and BMD levels for femoral neck (r=-0.14, P<0.001), total hip (r=-0.09, P<0.001) and trochanter (r=-0.13, P<0.001). In conclusion, we suggest that IGF-I rs2288377 polymorphism had a strong influence on osteoporosis susceptibility in this Chinese population.
Project description:This study assessed the interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and the interactions of gene and physical activity on handgrip strength, arm muscle mass-adjusted handgrip (armGrip), gait speed (GS), timed up and go (TUG), and leg press strength (LPS). Nine single nucleotide polymorphisms (SNPs) containing three IGF-1 SNPs (rs6214, rs5742692, and rs35767), two AKT2 SNPs (rs892119 and rs35817154), two FOXO1 SNPs (rs17446593 and rs10507486), and two FOXO3 SNPs (rs9480865 and rs2153960) were genotyped in 472 unrelated elders with a mean age of 73.8 years. We observed significant interactions of IGF-1 SNP rs6214 and rs35767 with regular physical activity on TUG and GS; and AKT2 SNP rs892119 and FOXO3 SNP rs9480865 with regular physical activity on armGrip. Genotype GG of IGF-1 rs6214 and rs35767 in individuals without regular physical activity had poor performance in TUG and GS, as well as GG of AKT2 rs892119 decreased armGrip in individuals without regular physical activity. After FDR adjustment, no significant gene-gene interactions were found. A sedentary lifestyle may increase the risk of impairing physical performance and regular physical activity is a remedy for sarcopenia, even a little regular physical activity can overcome carrying some risk alleles in this pathway.
Project description:Background: Recent studies have investigated the relationships between PLCE1 polymorphisms and cancer susceptibility. However, some findings lack consistency. Objectives: In the current study, we conducted a meta-analysis to more accurately evaluate the relationships between PLCE1 (rs2274223, rs3765524, rs753724, rs11187842, and rs7922612) single nucleotide polymorphisms (SNPs) and risk for different types of cancer. Methods: We performed a comprehensive search strategy in PubMed, Web of Science, Medline, EMbase, and Scopus for articles available until 19 March 2018. A total of 54 case-control studies comprising 17,955 cases and 20,400 controls were included in the current meta-analysis, which together comprised a total of 32 publications. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the PLCE1 polymorphisms and cancer susceptibility. All statistical analyses were performed using Stata 11 software. Results: Results of the meta-analysis demonstrated that the rs2274223 polymorphism showed a significant correlation with increased overall cancer susceptibility (AG vs. AA: OR 1.168, 95% CI 1.084-1.259; GG vs. AA: OR 1.351, 95% CI 1.163-1.570; AG+GG vs. AA: OR 1.193, 95% CI 1.103-1.290; GG vs. AA+AG: OR 1.262, 95% CI 1.102-1.446; G vs. A: OR 1.163, 95% CI 1.089-1.242). Results of subgroup analysis showed that the rs2274223 polymorphism was associated with higher risk for esophageal cancer and gastric cancer relative to colorectal cancer and head and neck cancer. In addition, the rs2274223 polymorphism was found to be associated with increased cancer risk, especially among the subgroups comprising Asians, studies with population-based controls, studies employing the TaqMan genotyping method, and studies consistent with Hardy-Weinberg equilibrium (HWE). The association between the rs3765524 polymorphism and reduced overall cancer risk was detected in one specific genetic model (CT vs. CC: OR 0.681, 95% CI 0.523-0.886). Results of subgroup analysis showed that the rs3765524 polymorphism was associated with cancer risk in a specific genetic model among the subgroups of colorectal cancer, esophageal cancer, Asians, studies with population-based controls, and studies consistent with HWE. However, relationships among the PLCE1 rs753724, rs11187842, and rs7922612 polymorphisms and tumor risk were not identified. Conclusions: Results of the current meta-analysis suggested that PLCE1 (rs2274223, rs3765524) polymorphisms are associated with cancer susceptibility.
Project description:It is reported that the iron-responsive element-binding protein 2 (IREB2) gene rs2568494 polymorphism might be associated with COPD risk. The purpose of this meta-analysis was to collect all eligible studies to review the association between IREB2 gene rs2568494 polymorphism and susceptibility to COPD.We carried out a comprehensive document search of electronic databases of PubMed, MEDLIN, Web of Science, and included 4 eligible studies that examined the association between IREB2 rs2568494 polymorphism and COPD susceptibility. We performed a meta-analysis of these studies based on IREB2 rs2568494 genotypes.After meta-analysis with fixed or random effects, no significant associations were found under the heterozygote model (GG/GA; OR=0.908, 95%CI: 0.790-1.043; P=0.172), homozygote model (GG/AA; OR=0.880, 95%CI: 0.497-1.557; P=0.661), dominant model (GG/AA+GA; OR=0.941, 95%CI: 0.748-1.182; P=0.599), or allelic model (G/A; OR=0.953, 95%CI: 0.770-1.179; P=0.655). However, we found a significant correlation under the recessive model (AA/GA+GG; OR=1.384, 95%CI: 1.092-1.755; P=0.007).The current results revealed that there was significant association between IREB2 gene rs2568494 polymorphism with susceptibility to COPD; the presence of allelic A might a genetic factor conferring susceptibility to COPD.
Project description:OBJECTIVE:It has been shown that Insulin-like growth factor-1 (IGF-1) may be related with bone mineral density (BMD) or osteoporosis. But there are few evidences on the role of genetic variation of IGF-1 on the BMD or osteoporosis. We observed the relationship between polymorphisms of IGF-1(rs35767, rs2288377 and rs5742612) with osteoporosis and BMD in the postmenopausal female population in our study. METHODS:A total of 216 postmenopausal women with a primary diagnosis of osteoporosis and 220 normal healthy women were included in the study. Genomic DNA of IGF-1 rs35767, rs2288377 and rs5742612 was extracted from the whole blood using QIAamp blood DNA mini kits (QIAGEN, Hilden, Germany) according to the methods recommended by the manufacturer. RESULTS:We found that T allele of rs35767 had higher increased risk of osteoporosis (OR=1.34, 95%CI=1.0-1.81). Those carrying T allele of rs35767 had a significant lower BMD at L1-L4 vertebrae, femoral neck, total hip and trochanter when compared with those carrying C allele (P < 0.05). In addition, the BMD of L1-L4 vertebrae, femoral neck, total hip and trochanter decreased by 2.09%, 3.74%, 3.52% and 2.54% in women carrying T alleles compared with those carrying C alleles. CONCLUSION:Our study suggests that polymorphism in IGF-I rs35767 was significantly associated with BMD and osteoporosis in postmenopausal female population, and polymorphism of rs35767 could be a marker for lower BMD and risk of osteoporosis.
Project description:We conducted a case-control study in a Chinese postmenopausal population, and explore the potential role of the promoter region variation of the IGF-1 gene in bone mineral density and osteoporosis risk. 485 postmenopausal women with a primary diagnosis of osteoporosis and 485 age-matched controls were selected between 2012 and 2014. The Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used for rs35767, rs2288377 and rs5742612 of IGF-1 genotyping. By conditional regression analysis, individuals carrying TT genotype and CT+TT genotype of rs35767 were found to be correlated with an elevated risk of osteoporosis, with adjusted ORs (95% CI) of 1.90 (1.23-2.93) and 1.35 (1.04-1.76), respectively. Our study found that CT+TT genotype of rs35767 was significantly associated with moderate increased risk of osteoporosis in smokers and drinkers, and the ORs (95% CI) were 2.11 (1.06-4.20) and 2.36 (1.29-4.32), respectively. We found that those carrying CT+TT genotype of rs35767 had a significant lower BMD levels at L1-L4 vertebrae, femoral neck, total hip and trochanter compared to those with CC genotype. Our study suggests that TT genotype and CT+TT genotype of IGF-I rs35767 were associated with risk of osteoporosis and BMD levels.
Project description:BACKGROUND:Ataxia telangiectasia mutated (ATM) gene plays a key role in response to DNA lesions and is related to the invasion and metastasis of malignancy. Epidemiological studies have indicated associations between ATM rs1801516 polymorphism and different types of cancer, but their results are inconsistent. To further evaluate the effect of ATM rs1801516 polymorphism on cancer risk, we conducted this meta-analysis. METHODS:Studies were identified according to specific inclusion criteria by searching PubMed, Web of Science, and Embase databases. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) under recessive, dominant, codominant, and overdominant models of inheritance were calculated to estimate the association between rs1801516 polymorphism and cancer risk. RESULTS:A total of 37 studies with 12,879 cases and 18,054 controls were included in our study. No significant association was found between rs1801516 polymorphism and cancer risk in overall comparisons (AA vs GG?+?GA: OR?=?0.91, 95% CI, 0.78-1.07; AA+GA vs GG: OR?=?1.00, 95% CI, 0.90-1.11; AA vs GG: OR?=?0.89, 95% CI, 0.75-1.06; GA vs GG: OR?=?1.01, 95% CI, 0.91-1.13; GG?+?AA vs GA: OR?=?1.00, 95% CI, 0.88-1.10). However, after subgroup analyses by region-specified population, significant associations were found in European (AA vs GG?+?GA: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017; AA vs GG: OR?=?0.79, 95% CI, 0.65-0.96, P?=?0.017), South American (AA+GA vs GG: OR?=?2.15, 95% CI, 1.37-3.38, P?=?0.001; GA vs GG: OR?=?2.19, 95% CI, 1.38-3.47, P?=?0.001; GG?+?AA vs GA: OR?=?0.46, 95% CI, 0.29-0.72, P?=?0.001), and Asian (AA vs GG?+?GA: OR?=?7.45, 95% CI, 1.31-42.46, P?=?0.024; AA vs GG: OR?=?7.40, 95% CI, 1.30-42.19, P?=?0.024). Subgroup analyses also revealed that compared with subjects carrying a GG genotype, those carrying a homozygote AA had a decreased risk for breast cancer (AA vs GG: OR?=?0.76, 95% CI, 0.59-0.98, P?=?0.035), and the homozygote AA was associated with decreased cancer risk in subjects with family history (AA vs GG: OR?=?0.68, 95% CI, 0.47-0.98, P?=?0.039). CONCLUSIONS:ATM rs1801516 polymorphism is not associated with overall cancer risk in total population. However, for subgroup analyses, this polymorphism is especially associated with breast cancer risk; in addition, it is associated with overall cancer risk in Europeans, South Americans, Asians, and those with family history.
Project description:<h4>Background</h4>The association between CD209 promoter polymorphisms (-336A/G, -871A/G) and tuberculosis (TB) risk has been widely reported, but results of previous studies remain controversial and ambiguous. To assess the association between CD209 polymorphisms and TB risk, a meta-analysis was performed.<h4>Methods</h4>Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, we identified outcome data from all articles estimating the association between CD209 polymorphisms and TB risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.<h4>Results</h4>A total of 14 studies with 3,610 cases and 3,539 controls were identified. There was no significant association between CD209 -336A/G polymorphism and TB risk (OR?=?1.04, 95% CI?=?0.91-1.19 for G vs. A; OR?=?1.13, 95% CI?=?0.84-1.53 for GG vs. AA; OR?=?1.04, 95% CI?=?0.87-1.24 for GG+AG vs. AA; OR?=?1.11, 95% CI?=?0.88-1.39 for GG vs. AG+AA). However, the significant association was revealed for Asians in GG vs. AA (OR?=?2.48, 95% CI?=?1.46-4.22, P?=?0.0008) and GG vs. AG+AA (OR?=?2.10, 95% CI?=?1.33-3.32, P?=?0.001). For the CD209 -871A/G polymorphism, lack of an association was also found (OR?=?0.81, 95% CI?=?0.70-0.95 for G vs. A; OR?=?1.00, 95% CI?=?0.52-1.93 for GG vs. AA; OR?=?0.73, 95% CI?=?0.60-0.89 for GG+AG vs. AA; OR?=?1.09, 95% CI?=?0.57-2.10 for GG vs. AG+AA).<h4>Conclusion</h4>The present meta-analysis suggested that CD209 promoter polymorphisms (-336A/G, -871A/G) were unlikely to substantially contribute to TB susceptibility. However, the GG genotype of CD209 -336A/G polymorphism might be a genetic risk factor that increases TB susceptibility for Asians in GG vs. AA and GG vs. AG+AA.