ArticlePloS one2018
Leptin gene variants and colorectal cancer risk: Sex-specific associations.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Role of Leptin as a Link between Asthma and Obesity: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2022Pooled it
- Preclinical Evidence of Probiotics in Colorectal Carcinogenesis: A Systematic Review.Digestive diseases and sciences · 2020Pooled it
- Obesity-Associated Colorectal Cancer.International journal of molecular sciences · 2024Review
- Mendelian randomization unraveled: gender-specific insights into obesity-related phenotypes and colorectal cancer susceptibility.Frontiers in endocrinology · 2024Article
- [Associations of circulating leptin levels with colorectal adenoma and colorectal cancer: a case-control and Mendelian randomization study].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Sex-Specific Associations between Adiponectin and Leptin Signaling and Pancreatic Cancer Survival.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023Article
- Review
- Association of higher plasma leptin levels with HOMA-IR index, high sensitivity C-reactive protein and glycolipid metabolism in patients with chronic schizophrenia: A multi-center cross-sectional study.Frontiers in psychiatry · 2022Article
- Article
- Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents.International journal of molecular sciences · 2021Review
- Leptin, Both Bad and Good Actor in Cancer.Biomolecules · 2021Review
- Serum lipid profiles and risk of colorectal cancer: a prospective cohort study in the UK Biobank.British journal of cancer · 2021Article
- Do Leptin Play a Role in Metabolism-Related Psychopathological Symptoms?Frontiers in psychiatry · 2021Article
- Review
Corrections and comments
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Authors and funding
19 authors at 12 institutions in 2 countries.
Funding
Abstract
backgroundHigh levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk.
methodsWe analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance.
resultsTwo variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men.
conclusionsLeptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.