Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PLoS One. 2013 Apr 8;8(4):e60777. doi: 10.1371/journal.pone.0060777. Print 2013.
Pathologic condition associated with metabolic syndrome traits seems to increase the risk of colorectal cancer. One mechanism underlying this relationship may involve the growth-promoting effects of the circulation hormones associated with obesity and insulin resistance, such as leptin.
METHODOLOGY/PRINCIPAL FINDINGS: A two-stage case-control study was used to explore the role of polymorphisms of Leptin (LEP) and Leptin receptor (LEPR), either alone or in combination with environmental factors in colorectal carcinogenesis. In stage 1, 20 single nucleotide polymorphisms (SNPs) that tag common SNPs in these two genes were genotyped among 470 cases and 458 controls. In stage 2, another population with 314 cases and 355 controls were genotyped for the two most promising SNPs from stage 1. LEPR rs12037879 only presented modestly increased colorectal cancer risk, with odds ratios of 1.41 (95% confidence interval [CI] 1.13-1.76) and 1.74 (95%CI 1.08-2.81) for GA and AA genotype when compared with GG genotype in combined population. Smokers carrying LEPR rs12037879 A allele presented 1.67-fold (95%CI 1.39-fold to 2.01-fold) increased colorectal cancer risk when compared with non-smokers carrying GG genotype in combined analysis. Individuals with family history of cancer harboring LEPR rs12037879 A allele showed 1.52-fold (95%CI: 1.24-fold to 1.86-fold) increased colorectal cancer risk, compared with individuals without family history of cancer harboring GG genotype. Multifactor gene-environment interaction analysis revealed significant interactions among LEPR rs12037879, LEPR rs6690625, smoking status and family history of cancer, exhibiting a gradient of increased colorectal cancer risk along with the increasing number of risk factors (P = 9.82 × 10(-10)).
CONCLUSIONS/SIGNIFICANCE: Our research supports that polymorphisms in LEPR may be associated with marginal increase in the risk for colorectal cancer. Moreover, this association could be strengthened by cigarette smoking and family history of cancer.
与代谢综合征特征相关的病理状况似乎会增加结直肠癌的风险。这种关系的一个机制可能涉及与肥胖和胰岛素抵抗相关的循环激素的促生长作用，例如瘦素。
方法/主要发现：采用两阶段病例对照研究探讨了瘦素（LEP）和瘦素受体（LEPR）的基因多态性，单独或与环境因素相结合在结直肠癌变中的作用。在第 1 阶段，对 470 例病例和 458 例对照中的 20 个单核苷酸多态性（SNP）进行了基因分型，这些 SNP 标记了这两个基因中的常见 SNP。在第 2 阶段，另一个人群中的 314 例病例和 355 例对照对第 1 阶段中两个最有前途的 SNP 进行了基因分型。与 GG 基因型相比，LEPR rs12037879 的 GA 和 AA 基因型仅略微增加了结直肠癌的风险，合并人群中的比值比分别为 1.41（95%置信区间[CI]1.13-1.76）和 1.74（95%CI1.08-2.81）。携带 LEPR rs12037879 A 等位基因的吸烟者与携带 GG 基因型的非吸烟者相比，结直肠癌风险增加了 1.67 倍（95%CI 1.39 倍至 2.01 倍）。携带 LEPR rs12037879 A 等位基因且有癌症家族史的个体与无癌症家族史且携带 GG 基因型的个体相比，结直肠癌风险增加了 1.52 倍（95%CI：1.24 倍至 1.86 倍）。多因素基因-环境交互作用分析显示，LEPR rs12037879、LEPR rs6690625、吸烟状况和癌症家族史之间存在显著的相互作用，随着危险因素数量的增加，结直肠癌的风险呈梯度增加（P=9.82×10（-10））。
结论/意义：我们的研究支持 LEPR 多态性可能与结直肠癌风险的适度增加有关。此外，这种关联可能会因吸烟和癌症家族史而加剧。
