PPARG rs3856806 C>T Polymorphism Increased the Risk of Colorectal Cancer: A Case-Control Study in Eastern Chinese Han Population.

Jing Lin,Gang Chen,Yu Chen,Xiong-Wei Zheng,Wei-Feng Tang,Sheng Zhang,Zeng-Qing Guo,Chao Liu

doi:10.3389/fonc.2019.00063

Abstract

Purpose: Functional variants in the peroxisome proliferator-activated receptor gamma (PPARG) and PPARG co-activator 1 (PPARGC1) family (e.g., PPARGC1A and PPARGC1B) genes were predicted to confer susceptibility to colorectal cancer (CRC). The aim of the present study was to explore the relationship between PPARG, PPARGC1A, PPARGC1B polymorphism and the risk of CRC.Patients and methods: We conducted a case-control study with 1,003 CRC cases and 1,303 controls. We selected the PPARG rs3856806 C>T, PPARGC1A rs2970847 C>T, rs8192678 C>T, rs3736265 G>A and PPARGC1B rs7732671 G>C and rs17572019 G>A SNPs to assess the relationship between PPARG, PPARGC1A, PPARGC1B their variants and risk of CRC.Results: We found that the PPARG rs3856806 C>T polymorphism increased the risk of CRC (TT vs. CC: adjusted OR, 1.59, 95% CI 1.08–2.35, P = 0.020; TT/CT vs. CC: adjusted OR, 1.26; 95% CI 1.06–1.49; P = 0.009 and TT vs. CC/CT: adjusted OR, 1.54; 95% CI 1.05–2.26; P = 0.028), even after a Bonferroni correction test. The stratified analysis revealed that the PPARG rs3856806 C>T polymorphism also increased the risk of CRC, especially in male, ≥61 years old, never smoking, never drinking, BMI ≥ 24 kg/m2, colon cancer and rectum cancer subgroups.Conclusion: Our findings highlight that the PPARG rs3856806 C>T polymorphism may increase the risk of CRC. In the future larger sample size case-control studies with a detailed functional assessment are needed to further determine the relationship of the PPARG rs3856806 C>T polymorphism with CRC risk.

Highlights

Colorectal cancer (CRC) is one of the most common type of malignancies, accounting for 1.8 million cases in GLOBOCAN 2018 [1]
The genotype distributions of peroxisome proliferator-activated receptor gamma (PPARG) rs3856806 C>T, PPARGC1A rs2970847 C>T, rs8192678 C>T, rs3736265 G>A, and PPARGC1B rs7732671 G>C and rs17572019 G>A are in accordance with Hardy-Weinberg equilibrium (HWE) in controls (P = 0.143, 0.925, 0.800, 0.059, 0.970, and 0.372, respectively)
Our findings suggested that the PPARG rs3856806 C>T polymorphism is associated with an increased risk of CRC, especially in male, ≥ 61 years old, never smoking, never drinking, body mass index (BMI) ≥24 kg/m2, colon cancer, and rectum cancer subgroups

Summary

Introduction

Colorectal cancer (CRC) is one of the most common type of malignancies, accounting for 1.8 million cases in GLOBOCAN 2018 [1]. The incidence of CRC is increasing in China, where it ranks as the fifth most common carcinoma in male and the fourth in female, with a total of 215,700 patients diagnosed in 2015 [2]. Epidemiologic investigations have attributed most of CRC to some important environmental factors [3]. The increase of the incidence of CRC is proposed to correlate with an unhealthy lifestyle, including drinking, smoking, low intake of dietary fiber, high intake of dietary fat, decreased consumption of vegetables, and fruits and being physically inactive [4,5,6,7]. Accumulating evidence highlighted that besides these unhealthy lifestyles and environmental factors, some additional inherited susceptibility factors may be associated with the development of CRC. As CRC is associated with obesity and Waist-to-Hip Ratio (WHR) [8,9,10], the peroxisome proliferator-activated receptor gamma (PPARG), PPARG co-activator 1 (PPARGC1) family (e.g., PPARGC1A and PPARGC1B) may be strong candidate genes predisposing to CRC [11]

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Conclusion