Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Luhn, Patricia; Dallal, Cher M.; Weiss, Jocelyn M.; Huang, Wen‐Yi; Lacey, J.; Hayes, Richard B.; Stanczyk, Frank Z.; Wentzensen, Nicolas; Brinton, Louise A.

doi:10.1097/01.ogx.0000435526.35453.45

Cited by 15 publications

(60 citation statements)

References 32 publications

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“…37,38 For conducting the dose-response meta-analysis, the following information were needed: (i) the distribution of cases and noncases and the risk estimates with the variance estimates for at least three quantitative exposure categories; (2) the median or mean level of these exposures in each category (if reported by ranges, mean level was calculated by averaging the lower and upper bound; if the lowest category was open ended, the lowest boundary was considered to be zero; if the highest category was open ended, the open-ended interval length was assumed to be the same as the adjacent interval). Given this, eight studies 16,19,20,[22][23][24][25]27 met the criteria and were included in the dose-response analysis of circulating adiponectin concentrations and endometrial cancer risk. However, limited by the number of studies met those criteria, 16,19,24 we failed to carry out the dose-response analysis of leptin and A/L ratio.…”

Section: Discussionmentioning

confidence: 99%

“…Given this, eight studies 16,19,20,[22][23][24][25]27 met the criteria and were included in the dose-response analysis of circulating adiponectin concentrations and endometrial cancer risk. However, limited by the number of studies met those criteria, 16,19,24 we failed to carry out the dose-response analysis of leptin and A/L ratio.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15] Evidence from epidemiologic studies investigating the relationship between circulating adiponectin and leptin concentrations and endometrial cancer risk has not been summarized. [16][17][18][19][20][21][22][23][24][25][26][27][28][29] Additionally, limited evidence from observational studies evaluating the A/L or L/A ratio and risk of endometrial cancer has been available to date. 16,19,21,22,24 Therefore, we carried out a meta-analysis of observational studies to systematically assess the overall aforementioned exposures with endometrial cancer risk.…”

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confidence: 99%

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Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

Gong

Wang

et al. 2015

Intl Journal of Cancer

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We performed this meta-analysis of epidemiologic studies to investigate the associations between circulating adiponectin, leptin and adiponectin-leptin (A/L) ratio and endometrial cancer risk. Relevant manuscripts were identified by searching PubMed and ISI Web of Science databases as well as by manual searching the references cited in retrieved manuscripts. Random-effects models were used to estimate summary odds ratio (SOR) and 95% confidence intervals (CIs) for aforementioned associations. Fourteen manuscripts with 13 studies (five nested case-control and eight case-control studies) cumulatively involving a total of 1,963 endometrial cancer cases and 3,503 noncases were included in the analyses. Overall, comparing persons with circulating concentrations of adiponectin, leptin and A/L ratio in the top tertile with persons with concentrations of these biomarkers in the bottom tertile yielded SORs of 0.47 (95% CI: 0.34-0.65; I 2 5 63.7%; n 5 13), 2.19 (95% CI: 1.44-3.31; I 2 5 64.2%; n 5 7),and 0.45 (95% CI: 0.24-0.86; I 2 5 90.1%; n 5 5), respectively. Notably, there was an 18% reduction in risk for per each 5 lg/mL increment in circulating adiponectin concentrations (SOR 5 0.82; 95% CI: 0.74-0.90; I 2 5 49%; n 5 8). Stratifying by study characteristics and whether these studies considered or adjusted for potential confounders, the findings were robust in the analyses of circulating adiponectin and leptin. No evidence of publication bias was detected. In conclusion, the findings from this metaanalysis suggest that increased circulating adiponectin and A/L ratio or decreased leptin concentrations were associated with reduced risk of endometrial cancer. Further prospective designed studies are warranted to confirm our findings.Endometrial cancer is the second most common gynecologic malignancy worldwide, with approximately 0.3 million new cases in 2012. 1 There is no doubt that obesity is a wellrecognized risk factor for this disease. Recently, the biological mechanisms linking obesity and endometrial cancer have largely centered on the aromatization of androgens in adipose tissue, leading to increased circulating estradiol levels 2 which have been the primary stimulants of endometrial proliferation. 3 However, this mechanism cannot fully explain the incidence of endometrial cancer in obese women. Experimental studies have provided evidence that adipokines, which are associated with hyperinsulinemia and degree of insulin resistance independent of adiposity, are also involved in the development of endometrial cancer.Adipose tissue was previously considered to be an energystorage site. During recent decades, this tissue has been found to be an endocrine organ producing and secreting several bioactive peptides, including adipokines such as adiponectin and leptin. 4 Biological studies have shown that adiponectin, the most abundant adipokine, is not only inversely associated with obesity as well as hyperinsulinemia 5,6 but appears to have anti-inflammatory, antiangiogenic and antidiabetic properties 7,8 ; In contrast,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

Gong

Wang

et al. 2015

Intl Journal of Cancer

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“…BMI: body mass index. 5 Recent BMI models not adjusted for recent BMI. 6 Wald test for interaction between body size and postmenopausal hormone use (examined in base multivariate model).…”

Section: Epidemiologymentioning

confidence: 99%

Prospective study of body size throughout the life-course and the incidence of endometrial cancer among premenopausal and postmenopausal women

et al. 2015

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Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 members of the Nurses’ Health Study (NHS) and 105,386 of the Nurses’ Health Study II (NHS II) recalled their body fatness at ages 5, 10, and 20 using a pictogram. Childhood and adolescent body fatness were derived as the average at ages 5 and 10, and ages 10 and 20, respectively. We obtained adult weight from concurrent questionnaires. We calculated hazard ratios (HR) of endometrial cancer using Cox proportional hazards models. During follow-up, 757 incident cases of endometrial cancer were diagnosed. Body fatness in childhood, at age 10, in adolescence, and at age 20 were positively associated with endometrial cancer risk (HR for ≥ Level 5 versus ≤ Level 2 in adolescence: 1.83 (95% CI 1.41-2.37). After adjusting for most recent BMI, none of the associations persisted. Weight change since age 18 was positively associated with endometrial cancer risk [HR for ≥ 25 kg gain versus stable: 2.54 (95% CI 1.80-3.59). Adult BMI was strongly associated with endometrial cancer risk [HR BMI ≥ 35 kg/m2 versus BMI ≤ 25 kg/m2: 4.13 (95% CI 3.29-5.16)]. In postmenopausal women, the association with BMI was significantly stronger among non-users of hormone therapy. In conclusion, obesity throughout life is positively associated with endometrial cancer risk, with adult obesity one of the strongest risk factors. Maintaining a healthy weight throughout life remains important.

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“…(14) Additionally, epidemiological studies found that lower serum adiponectin levels were linked with an increased incidence of cancers of the colon, breast, and endometrium. (15)(16)(17) Several SNPs in the gene encoding adiponectin (ADIPOQ) were associated with increased prostate cancer risk in Caucasians, (18) of which rs266729 was previously shown to be associated with an enhanced risk of lung, colon, and breast cancers. (19)(20)(21)(22) Recently, genetic variants of rs266729 and rs182052 SNPs were found to be associated not only with prostate cancer risk but also with different circulating adiponectin levels.…”

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confidence: 99%

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma

Zhang

Zhu

et al. 2015

Cancer Science

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Recent studies have indicated that low circulating adiponectin concentrations are associated with a higher risk of several cancers, including renal cell carcinoma. In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell renal cell carcinoma (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). The association of serum adiponectin concentration with genetic variants was calculated using a multivariate linear regression model. A significantly higher ccRCC risk was associated with the rs182052 variant A allele (adjusted OR, 1.36 and 95% CI, 1.07–1.74 for AA vs GG, P = 0.013; adjusted OR, 1.27 and 95% CI, 1.04–1.56 for AA vs GG+AG, P = 0.019), and this positive association was more evident in overweight subjects. Fasting serum adiponectin was lower in subjects carrying A alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.In this case–control study, we examined the frequency of single nucleotide polymorphisms (rs182052G>A, rs266729C>G, and rs3774262G>A) in the adiponectin gene (ADIPOQ) in 1004 patients with clear cell RCC (ccRCC) compared with a group of healthy subjects (n = 1108). Fasting serum adiponectin concentrations were also examined. Fasting serum adiponectin was lower in subjects carrying minor alleles of rs182052 in both ccRCC patients (β = −0.399, P = 0.018) and healthy controls (β = −0.371, P = 0.024). These results suggest that ADIPOQ rs182052 is significantly associated with ccRCC risk.

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Circulating Adipokine Levels and Endometrial Cancer Risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract: Background-Circulating adipokine levels may be associated with endometrial cancer risk, yet few studies have evaluated these markers prospectively.

Cited by 15 publications

References 32 publications

Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

Circulating adiponectin, leptin and adiponectin–leptin ratio and endometrial cancer risk: Evidence from a meta‐analysis of epidemiologic studies

Prospective study of body size throughout the life-course and the incidence of endometrial cancer among premenopausal and postmenopausal women

ADIPOQ polymorphism rs182052 is associated with clear cell renal cell carcinoma

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