Adiponectin gene and risk of colorectal cancer.
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ABSTRACT:
SUBMITTER: Gornick MC
PROVIDER: S-EPMC3170961 | biostudies-literature | 2011 Aug
REPOSITORIES: biostudies-literature
Publications
Adiponectin gene and risk of colorectal cancer.
Gornick M C MC Rennert G G Moreno V V Gruber S B SB
British journal of cancer 20110801 4
<h4>Background</h4>Genes of the adiponectin pathway are interesting candidates for colorectal cancer risk based on the potential association between colorectal cancer and obesity. However, variants of the adiponectin gene (ADIPOQ) have been demonstrated to be inconsistently associated with risk of colorectal cancer.<h4>Methods</h4>The current study attempted to evaluate these findings by examining several single nucleotide polymorphisms (SNPs) that were previously genotyped as part of a genome-w ...[more]
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Project description:BackgroundThis meta-analysis investigates the associations of adiponectin (ADIPOQ) genetic polymorphisms with the susceptibility to colorectal cancer (CRC).Material and methods2 reviewers independently searched 6 databases - PubMed, Cochrane Library, Ovid, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases - to identify published studies relevant to adiponectin gene polymorphisms and CRC. Studies retrieved from database searches were screened using our stringent inclusion and exclusion criteria. Full texts of the selected studies were accessed and related data was extracted using a standardized data extraction form. Comprehensive Meta-analysis 2.0 software was used for statistical analyses.ResultsA total of 188 studies were initially retrieved from database search, and 6 studies were eventually selected, through a rigorous screening process, for inclusion in this meta-analysis. The 6 studies contained a total of 1897 patients (Asians: 1190; white: 707) with CRC in case group and 2475 healthy controls (Asians: 1325; white: 1150) in the control group. Results of the current meta-analysis revealed that the rs2241766 T>G single-nucleotide polymorphisms (SNP) increase the risk of CRC; rs1501299 G>T under dominant model was associated with increased risk of CRC; and rs266729 C>G SNP under allele model conferred an increased risk of CRC.ConclusionsOur meta-analysis strongly suggests that the ADIPOQ rs2241766 T>G, rs1501299 G>T, and rs266729 C>G SNPs correlate with an increased risk of CRC.
| S-EPMC4562615 | biostudies-literature
Project description:Circulating adiponectin has been associated with lower risk of colorectal cancer (CRC). Genome-wide association studies have identified several single-nucleotide polymorphisms (SNPs) associated with adiponectin levels. However, it is unclear whether these SNPs are associated with CRC risk. In addition, previous data on SNPs in the adiponectin pathway and their associations with CRC are inconsistent. Therefore, we examined 19 SNPs in genes related to adiponectin or its receptors and their associations with CRC using logistic regression among 7,020 cases and 7,631 controls drawn from ten studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium. Using data from a subset of two large cohort studies, we also assessed the contribution of individual SNPs and an adiponectin genetic score to plasma adiponectin after accounting for lifestyle factors among 2,217 women and 619 men. We did not find any statistically significant association between the 19 adiponectin-associated SNPs and CRC risk (multivariable-adjusted odds ratios ranged from 0.89 to 1.05, all p?>?0.05). Each SNP explained less than 2.50% of the variance of plasma adiponectin, and the genetic score collectively accounted for 2.95 and 1.42% of the variability of adiponectin in women and men, respectively, after adjustment for age, body mass index, physical activity, smoking, alcohol consumption, regular use of aspirin or nonsteroidal anti-inflammatory drug and postmenopausal hormone use. In conclusion, our findings do not support an association between known adiponectin-related common SNPs and CRC incidence. However, known common SNPs account for only a limited proportion of the interindividual variance in circulating adiponectin. Further work is warranted to investigate the relationship between adiponectin and CRC while accounting for other components in the pathway.
| S-EPMC4405454 | biostudies-literature
Project description:ObjectiveThe adiponectin gene (ADIPOQ) has been suggested to be associated with the pathogenesis of colorectal cancer (CRC). However, the results have been inconsistent. In this study, we performed a meta-analysis to investigate the association between adiponectin polymorphisms and CRC risk.MethodsAll eligible case-control studies published up to March 2013 were identified by searching PubMed, Web of Science and CNKI. Effect sizes of odds ratio (OR) and 95% confidence interval (95% CI) were calculated by using a fixed- or random-effect model.ResultsA total of 9 case-control studies were included, Of those studies, there were eight studies (2024 cases and 2777 controls) for rs1501299G/T polymorphism, five studies (1401 cases and 1691 controls) for rs2241766T/G polymorphism, five studies (2945 cases and 3361 controls) for rs266729C/G polymorphism, three studies (1221 cases and 1579 controls) for rs822395A/C polymorphism and three studies (1222 cases and 1575 controls) for rs822396A/G polymorphism. Overall, a significant association was observed for rs2241766T/G polymorphism under heterozygote comparison (TG vs. TT: OR=1.22, 95%CI: 1.05-1.43); while there was no significant association for rs2241766 polymorphism under other genetic models, and for other four polymorphisms under all genetic models. Besides, when stratified analyses by ethnicity, no significant association between five polymorphisms and CRC risk were observed under all genetic models among Asian, Caucasian and African-American.ConclusionsThis meta-analysis indicated that adiponectin rs2241766T/G rather than rs1501299G/T, rs266729C/G, rs822395A/C and rs822396A/G polymorphism was associated with the risk of colorectal cancer.
| S-EPMC3714387 | biostudies-literature
Project description:To discuss the association between adiponectin (ADIPOQ) gene rs2241766 and rs1501299 polymorphisms and the risk of colorectal cancer, and to analyze the role of the interaction between these two loci and environmental factors in colorectal cancer pathogenesis.The case-control study was performed with a 1:1 match. A self-designed questionnaire was used to perform a face-to-face survey with 600 new primary colorectal cancer cases confirmed by histopathology as well as 600 cases of people receiving a physical examination at the same time. The general information, lifestyle, and diet habits, etc. were collected from two groups of study subjects. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify ADIPOQ rs2241766 and rs1501299 genotypes.After adjusting for factors such as colorectal cancer family history, body-mass index (BMI), daily sedentary time, weekly red meat intake frequency, as well regular tea drinking, conditional logistic regression analysis indicated that rs2241766 TG+GG carriers had a higher risk of colorectal cancer than TT carriers (OR=1.433, 95% CI: 1.014-1.985); rs1501299 GT+TT carriers had a lower risk of colorectal cancer than GG carriers (OR=0.723, 95% CI: 0.531-0.902). Generalized multifactor dimensionality reduction analysis showed that ADIPOQ rs2241766 and rs1501299 could have interaction with red meat intake (p=0.001).ADIPOQ rs2241766 and rs1501299 single nucleotide polymorphisms (SNPs) could be associated with colorectal pathogenesis and could have interactions with red meat intake. Both factors impact colorectal cancer occurrence.
| S-EPMC4278080 | biostudies-literature
Project description:CONTEXT:Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date. OBJECTIVE:To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk. DESIGN, SETTING, AND PATIENTS:Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity. MAIN OUTCOME MEASURES:ADIPOQ and ADIPOR1 SNP frequency among cases and controls. RESULTS:In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99). CONCLUSION:The SNP rs266729, which tags the 5' flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.
| S-EPMC2628475 | biostudies-literature
Project description:Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing characteristics. It remains unclear whether adiponectin may influence colorectal cancer development.To determine whether prediagnostic levels of adiponectin were associated with risk of incident colorectal cancer in the Women's Health Study, we conducted a nested case-control study of 275 colorectal cancer cases and 275 matched controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Multivariable logistic regression with adjustment for colorectal cancer risk factors was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence and mortality by adiponectin quartiles based on the control distribution.Median plasma adiponectin level was similar in cases versus controls (6.00 vs. 6.24 ?g/mL). In multivariable-adjusted logistic regression models, high plasma adiponectin levels were not significantly associated with risk of colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48-1.56), p trend = 0.63].These results suggest no appreciable association between plasma adiponectin and risk of colorectal cancer in women. Confirmation of these observations in larger studies is needed.
| S-EPMC4466025 | biostudies-literature
Project description:BACKGROUND: Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48-2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78-7.34), 3.18 (95%CI: 1.73-5.82) and 1.97 (95%CI: 1.27-3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18-fold (95%CI:0.89-fold to 1.58-fold), 1.87-fold (95%CI: 1.38-fold to 2.54-fold) and 4.39-fold (95%CI: 2.75-fold to 7.01-fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P(trend) <0.0001). CONCLUSIONS/SIGNIFICANCE: Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.
| S-EPMC3210156 | biostudies-literature
Project description:Adipokines are adipocyte-secreted hormones that may mediate the etiologic link between obesity and colorectal cancer; however, the evidence from large prospective studies is limited. We prospectively evaluated the association of plasma adiponectin and soluble leptin receptor (sOB-R) with colorectal cancer risk within the Nurses' Health Study (1990-2008) and the Health Professionals Follow-up Study (1994-2008) among 616 incident colorectal cancer cases and 1,205 controls selected using risk-set sampling and matched on age and date of blood draw. In unconditional logistic regression with adjustment for matching factors and multiple risk factors, plasma adiponectin was significantly associated with reduced risk of colorectal cancer among men, but not among women. Compared with men in the lowest quartile of adiponectin, men in the highest quartile had a relative risk (RR) for colorectal cancer of 0.55 [95% confidence interval (CI), 0.35-0.86; Ptrend = 0.02]. The corresponding RR in women was 0.96 (95% CI, 0.67-1.39; Ptrend = 0.74). Plasma sOB-R was not associated with overall colorectal cancer risk in either men or women. A significant heterogeneity was noted in the association between sOB-R and colorectal cancer by subsite in women (Pheterogeneity = 0.004); sOB-R was significantly associated with increased risk of rectal cancer but not colon cancer. These findings support a role for adiponectin in colorectal carcinogenesis in men. Further studies are warranted to confirm these associations and elucidate potential underlying mechanisms.
| S-EPMC3772620 | biostudies-literature
Project description:BackgroundLow levels of adiponectin (ADIPOQ; HGNC ID; HGNC:13633), an adipokine, are associated with obesity, adiposity, excess energy balance, and increased risk of colorectal neoplasia. Given the reported association of increased body mass index (BMI) and low-level physical activity with KRAS-mutated colorectal tumor, we hypothesized that low-level plasma adiponectin might be associated with increased risk of KRAS-mutant colorectal carcinoma but not with risk of KRAS wild-type carcinoma.MethodsWe conducted molecular pathological epidemiology research using a nested case-control study design (307 incident rectal and colon cancer case patients and 593 matched control individuals) within prospective cohort studies, the Nurses' Health Study (152 case patients and 297 control individuals, with blood collection in 1989-1990) and the Health Professionals Follow-up Study (155 case patients and 296 control individuals, with blood collection in 1993-1995). Multivariable conditional logistic regression models and two-sided likelihood ratio tests were used to assess etiologic heterogeneity of the associations.ResultsThe association of low-level plasma adiponectin with colorectal cancer risk statistically significantly differed by KRAS mutation status (P heterogeneity = .004). Low levels of plasma adiponectin were associated with KRAS-mutant colorectal cancer (for the lowest vs highest tertile: multivariable odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.50 to 5.34, P trend = .002) but not with KRAS wild-type cancer (for the lowest vs highest tertile: multivariable OR = 0.83, 95% CI = 0.49 to 1.43, P trend = .48). In secondary analyses, the association between plasma adiponectin and colorectal cancer did not appreciably differ by BRAF or PIK3CA oncogene mutation status.ConclusionsLow-level plasma adiponectin is associated with KRAS-mutant colorectal cancer risk but not with KRAS wild-type cancer risk.
| S-EPMC4668768 | biostudies-literature
Project description:BACKGROUND:Colorectal cancer (CRC) is the fourth leading cause of cancer-related death around the world and accumulated evidence indicates the association between CRC and obesity and insulin resistance. OBJECTIVES:Regarding the role of adiponectin in obesity and insulin resistance, we explored whether genetic variants in adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) are associated with CRC risk. MATERIALS AND METHODS:ADIPOQ (rs2241766) and ADIPOR1 (rs2275738) gene variants were genotyped in 261 cases with CRC and 339 controls using PCR-RFLP method. RESULTS:In this study, no significant difference was observed for ADIPOQ gene rs2241766 variant between the cases and controls. However, carriers of the ADIPOR1 (rs2275738) "CC + CT" genotype compared with "TT" genotype occurred more frequently in the cases with CRC than the controls, and the difference remained significant after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC (P = 0.048; OR = 1.49, 95%CI = 1.01-2.20). Interestingly, after adjustment for confounding factors the ADIPOR1 "CC + TC" genotype compared with "TT" genotype was also associated with an increased risk for obesity in the cases (P = 0.040; OR = 1.86, 95%CI = 1.03-3.36). CONCLUSIONS:Our findings suggest for the first time that the - 106 C > T (rs2275738) variant of ADIPOR1 gene may be a genetic contributor to CRC and obesity risk in the cases with CRC. However, further studies with bigger sample size are needed to validate these findings.
| S-EPMC5006128 | biostudies-literature