Barot Shabane, Vermani Litika, Blom Johannes, Larsson Susanna, Liljegren Annelie, Lindblom Annika
Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology, Södersjukhuset, Stockholm, Sweden.
Clin Transl Gastroenterol. 2025 Jan 1;16(1):e00790. doi: 10.14309/ctg.0000000000000790.
65%-70% of colorectal cancer (CRC) cases are considered sporadic; they arise under the influence of environmental factors in individuals lacking a family history of CRC. Low-risk genetic variants are believed to contribute to CRC risk, in tandem with lifestyle factors.
Six hundred sixteen nonfamilial Swedish CRC cases with at least 1 of the following 5 risk factors: smoking, excessive alcohol consumption, physical inactivity, adherence to an unhealthy diet, and excess body weight were included in this study. A control group consisting of 1,642 healthy individuals was used. Cases and controls were genotyped from blood samples at the Centre for Inherited Disease Research at Johns Hopkins University within the Colorectal Transdisciplinary Study research collaboration, using the Illumina Infinium OncoArray-500 K BeadChip. Five separate genome-wide haplotype association analyses were performed, one for each risk factor. Logistic regression models were used to estimate associations between haplotypes (exposure) and CRC (outcome) in cases with lifestyle risk factors vs controls. Haplotypes with an odds ratio >1 were considered candidate risk markers, denoting an area of interest in the genome. A significance threshold of P < 5 × 10 -8 was used.
We found 17 haplotype regions significantly associated with CRC in cases vs controls. Several regions included genes linked to inflammation and tumor promotion.
We concluded that having certain genetic variants was associated with an increased risk of CRC compared with healthy controls among cases with known lifestyle risk factors. The interplay of lifestyle and genetic risk factors calls for further elucidation.
65% - 70%的结直肠癌（CRC）病例被认为是散发性的；它们在缺乏CRC家族史的个体中，受环境因素影响而发生。低风险基因变异被认为与生活方式因素一起，会增加患CRC的风险。
本研究纳入了616例非家族性瑞典CRC病例，这些病例至少具有以下5种风险因素中的一种：吸烟、过量饮酒、缺乏体育锻炼、坚持不健康饮食和体重超标。使用了一个由1642名健康个体组成的对照组。在结直肠癌跨学科研究合作项目中，通过约翰霍普金斯大学遗传疾病研究中心，对病例组和对照组的血样进行基因分型，采用Illumina Infinium OncoArray - 500K BeadChip芯片。进行了5项独立的全基因组单倍型关联分析，每项分析针对一种风险因素。使用逻辑回归模型来估计有生活方式风险因素的病例组中，单倍型（暴露因素）与CRC（结局）之间的关联。比值比>1的单倍型被视为候选风险标志物，表明该基因组区域值得关注。使用的显著性阈值为P < 5×10 -8。
我们发现17个单倍型区域在病例组与对照组中与CRC显著相关。几个区域包含与炎症和肿瘤促进相关的基因。
我们得出结论，在有已知生活方式风险因素的病例中，与健康对照组相比，具有某些基因变异会增加患CRC的风险。生活方式和遗传风险因素之间的相互作用需要进一步阐明。
