Cho Young Ae, Lee Jeonghee, Oh Jae Hwan, Chang Hee Jin, Sohn Dae Kyung, Shin Aesun, Kim Jeongseon
Molecular Epidemiology Branch, National Cancer Center, Goyang, South Korea.
Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, South Korea.
Oncotarget. 2017 Jan 31;8(5):8550-8558. doi: 10.18632/oncotarget.14347.
The role of inflammation in colorectal carcinogenesis may differ according to individuals' genetic variations. Therefore, we investigated whether genetic susceptibility alters the association between inflammatory potential of diet and the risk of colorectal cancer within the Korean population. We genotyped four polymorphisms in four genes (IL1B, TNF, PPARG, and PPARGC1A) and calculated the dietary inflammatory index (DII) in a case-control study with 701 colorectal cancer patients and 1,402 controls. Among the investigated polymorphisms, heterozygous carriers of rs3774921 in PPARGC1A showed a higher risk of colorectal cancer (OR [95% CI] = 1.26 [1.02-1.55] for TC vs. TT). When the data were stratified by rs3774921 genetic variant, the association of a pro-inflammatory diet with colorectal cancer risk was more prominent among homozygous variant allele carriers (OR [95% CI] = 5.15 [2.35-11.29] for high vs. low DII) (P for interaction = 0.009). When stratified by anatomic site, this association was much stronger for rectal cancer patients (OR [95% CI] = 8.06 [2.67-24.16] for high vs. low DII) (P for interaction = 0.006). Additionally, this interaction was stronger among those older than 50 years and not exercising regularly. Conversely, no association or interaction was found for the other investigated polymorphisms. In conclusion, the results of this study suggest that a pro-inflammatory diet may have a differential effect on colorectal cancer risk based on PPARGC1A genetic variation. This interaction may differ by anatomic location and other risk factors.
炎症在结直肠癌发生过程中的作用可能因个体基因变异而有所不同。因此，我们调查了遗传易感性是否会改变韩国人群中饮食炎症潜能与结直肠癌风险之间的关联。在一项包含701例结直肠癌患者和1402例对照的病例对照研究中，我们对四个基因（IL1B、TNF、PPARG和PPARGC1A）中的四个多态性进行了基因分型，并计算了饮食炎症指数（DII）。在所研究的多态性中，PPARGC1A基因中rs3774921的杂合携带者患结直肠癌的风险更高（TC与TT相比，OR[95%CI]=1.26[1.02 - 1.55]）。当数据按rs3774921基因变异分层时，促炎饮食与结直肠癌风险之间的关联在纯合变异等位基因携带者中更为显著（高DII与低DII相比，OR[95%CI]=5.15[2.35 - 11.29]）（交互作用P值=0.009）。按解剖部位分层时，这种关联在直肠癌患者中更强（高DII与低DII相比，OR[95%CI]=8.06[2.67 - 24.16]）（交互作用P值=0.006）。此外，这种交互作用在年龄大于50岁且不经常锻炼的人群中更强。相反，对于其他所研究的多态性，未发现关联或交互作用。总之，本研究结果表明，基于PPARGC1A基因变异，促炎饮食可能对结直肠癌风险有不同影响。这种交互作用可能因解剖位置和其他风险因素而异。
