Lu Y-Thanh, Gunathilake Madhawa, Lee Jeonghee, Kim Youngyo, Oh Jae Hwan, Chang Hee Jin, Sohn Dae Kyung, Shin Aesun, Kim Jeongseon
Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, South Korea.
Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, South Korea.
Carcinogenesis. 2022 Apr 25;43(3):203-216. doi: 10.1093/carcin/bgac007.
The bioactive compounds in coffee have several antioxidant properties that may beneficially impact colorectal cancer (CRC) development. The aryl hydrocarbon receptor (AhR) is an important transcription factor that regulates an enzyme related to the caffeine metabolism pathway. We investigated the modification effect on coffee of AhR gene polymorphism in the risk of CRC. A case-control study was conducted with 699 cases and 1393 controls to investigate the interaction between coffee intake and the AhR rs2066853 variant in CRC risk. The odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using multiple logistic regression analyses. We observed a significant protective effect of coffee against CRC in the overall and male populations. Consuming three or more cups of coffee per day may significantly lower CRC risk in all subjects by 77% and in men by 83% (OR = 0.23, 95% CI: 0.14-0.39 and OR = 0.17, 95% CI: 0.09-0.34, respectively, P-trends < 0.001). No association between AhR rs2066853 and CRC risk was found. In the dominant model, the G/G genotype had a strongest synergistic effect with coffee on protection against CRC (OR = 0.12, 95% CI: 0.06-0.26, P-interaction = 0.014). The interaction remained significant in men and the distal colon cancer subgroup. In the additive model, the interaction was clearly shown strongest in G/G carriers (OR = 0.12, 95% CI: 0.06-0.27, P-interaction = 0.039), followed by A/A and G/A carriers. The interaction remained significant in men and the rectal cancer subgroup. In conclusion, the protective effect of coffee on CRC risk might interact with the genetic variant AhR rs2066853, and this joint effect was determined by sex and site-specific cancer.
咖啡中的生物活性化合物具有多种抗氧化特性，可能对结直肠癌（CRC）的发展产生有益影响。芳烃受体（AhR）是一种重要的转录因子，可调节与咖啡因代谢途径相关的一种酶。我们研究了AhR基因多态性对咖啡在CRC风险方面的修饰作用。开展了一项病例对照研究，纳入699例病例和1393例对照，以调查咖啡摄入量与AhR rs2066853变体在CRC风险中的相互作用。使用多因素逻辑回归分析评估比值比（OR）和95%置信区间（CI）。我们在总体人群和男性人群中观察到咖啡对CRC具有显著的保护作用。每天饮用三杯或更多杯咖啡可能使所有受试者的CRC风险显著降低77%，男性降低83%（OR分别为0.23，95%CI：0.14 - 0.39和OR = 0.17，95%CI：0.09 - 0.34，P趋势<0.001）。未发现AhR rs2066853与CRC风险之间存在关联。在显性模型中，G/G基因型与咖啡对CRC的保护作用具有最强的协同效应（OR = 0.12，95%CI：0.06 - 0.26，P相互作用 = 0.014）。这种相互作用在男性和远端结肠癌亚组中仍然显著。在相加模型中，G/G携带者的相互作用最为明显（OR = 0.12，95%CI：0.06 - 0.27，P相互作用 = 0.039），其次是A/A和G/A携带者。这种相互作用在男性和直肠癌亚组中仍然显著。总之，咖啡对CRC风险的保护作用可能与基因变体AhR rs2066853相互作用，并且这种联合效应由性别和特定部位癌症决定。
