Colorectal Cancer Group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona 08907, Spain.
Mutagenesis. 2012 Mar;27(2):169-76. doi: 10.1093/mutage/ger066.
Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included dietary fat intake; consequently, the role of genes in the fatty acid biosynthesis and metabolism pathways is of particular interest. Moreover, hyperlipidaemia has been associated with different type of cancer and serum lipid levels could be affected by genetic factors, including polymorphisms in the lipid metabolism pathway. The aim of this study is to assess the association between single-nucleotide polymorphisms (SNPs) in fatty acid metabolism genes, serum lipid levels, body mass index (BMI) and dietary fat intake and CRC risk; 30 SNPs from 8 candidate genes included in fatty acid biosynthesis and metabolism pathways were genotyped in 1780 CRC cases and 1864 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. Several LIPC (lipase, hepatic) polymorphisms were found to be associated with CRC risk, although no particular haplotype was related to CRC. The SNP rs12299484 showed an association with CRC risk after Bonferroni correction. We replicate the association between the T allele of the LIPC SNP rs1800588 and higher serum high-density lipoprotein levels. Weak associations between selected polymorphism in the LIPC and PPARG genes and BMI were observed. A path analysis based on structural equation modelling showed a direct effect of LIPC gene polymorphisms on colorectal carcinogenesis as well as an indirect effect mediated through serum lipid levels. Genetic polymorphisms in the hepatic lipase gene have a potential role in colorectal carcinogenesis, perhaps though the regulation of serum lipid levels.
结直肠癌（CRC）是全球癌症死亡的主要原因。CRC 的流行病学风险因素包括膳食脂肪摄入；因此，脂肪酸生物合成和代谢途径中的基因作用尤其引人注目。此外，高脂血症与不同类型的癌症有关，血清脂质水平可能受遗传因素的影响，包括脂质代谢途径中的多态性。本研究旨在评估脂肪酸代谢基因中单核苷酸多态性（SNPs）、血清脂质水平、体重指数（BMI）和膳食脂肪摄入与 CRC 风险之间的关联；从脂肪酸生物合成和代谢途径中包含的 8 个候选基因中选择了 30 个 SNP，在来自分子流行病学结直肠癌研究的 1780 例 CRC 病例和 1864 例匹配对照中进行了基因分型。还获得了关于临床病理特征、生活方式和饮食习惯的信息。进行了逻辑回归和关联分析。尽管没有特定的单倍型与 CRC 相关，但发现几种 LIPC（脂肪酶，肝）多态性与 CRC 风险相关。在 Bonferroni 校正后，SNP rs12299484 与 CRC 风险相关。我们复制了 LIPC SNP rs1800588 的 T 等位基因与较高的血清高密度脂蛋白水平之间的关联。在 LIPC 和 PPARG 基因中选择的多态性与 BMI 之间观察到微弱的关联。基于结构方程模型的路径分析显示，LIPC 基因多态性对结直肠发生具有直接影响，以及通过血清脂质水平介导的间接影响。肝脂肪酶基因中的遗传多态性可能在结直肠发生中起作用，可能是通过调节血清脂质水平。
