Background/Objectives: One of the fastest-growing minority groups in the U.S. is the Hispanic/Latino population. Recent studies have shown how this population is being disproportionately affected by early-onset colorectal cancer (CRC). Compared to corresponding non-Hispanic White (NHW) patients, Hispanic/Latino patients have both higher incidence of disease and rates of mortality. Two well-established drivers of early-onset CRC in the general population are alterations in the WNT and TGF-Beta signaling pathways; however, the specific roles of these pathways in Hispanics/Latinos are poorly understood. Methods: Here, we assessed CRC mutations in the WNT and TGF-Beta pathways by conducting a bioinformatics analysis using cBioPortal. Cases of CRC were stratified both by age and ethnicity: (1) early-onset was defined as <50 years vs. late-onset as ≥50 years; (2) we compared early-onset in Hispanics/Latinos to early-onset in NHWs. Results: No significant differences were evident when we compared early-onset and late-onset CRC cases within the Hispanic/Latino cohort. These results are consistent with findings from large cohorts that do not specify ethnicity. However, we found significant differences when we compared early-onset CRC in Hispanic/Latino patients to early-onset CRC in NHW patients: specifically, alterations in the gene bone morphogenetic protein-7 (BMP7) were more frequent in early-onset CRC for the Hispanic/Latino patients. In addition to these findings, we observed that both NHW patients and Hispanic/Latino patients with early-onset disease had better clinical outcomes when there was evidence of WNT pathway alterations. Conversely, the absence of TGF-Beta pathway alterations was uniquely associated with improved outcomes exclusively in early-onset Hispanic/Latino patients. Conclusions: In toto, these findings underscore how the WNT and TGF-Beta pathways may act differently in different ethnic groups with early-onset CRC. These findings may set a stage for developing new therapies tailored for reducing cancer health disparities.
背景/目的：西班牙裔/拉丁裔是美国增长最快的少数族裔群体之一。近期研究表明，该群体正受到早发性结直肠癌的不成比例影响。与非西班牙裔白人患者相比，西班牙裔/拉丁裔患者的发病率和死亡率均更高。WNT和TGF-β信号通路改变是普通人群中早发性结直肠癌的两个明确驱动因素，但这些通路在西班牙裔/拉丁裔人群中的具体作用尚不清楚。方法：本研究通过cBioPortal进行生物信息学分析，评估结直肠癌中WNT和TGF-β通路的基因突变情况。病例按年龄和种族分层：（1）早发性定义为<50岁，晚发性定义为≥50岁；（2）比较西班牙裔/拉丁裔早发性患者与非西班牙裔白人早发性患者。结果：在西班牙裔/拉丁裔队列中，早发性与晚发性结直肠癌病例未发现显著差异，该结果与未区分种族的大型队列研究结论一致。然而，西班牙裔/拉丁裔早发性患者与非西班牙裔白人早发性患者比较存在显著差异：具体表现为西班牙裔/拉丁裔早发性患者中骨形态发生蛋白7基因的改变更为频繁。此外，研究还发现无论非西班牙裔白人还是西班牙裔/拉丁裔早发性患者，当存在WNT通路改变证据时均表现出更好的临床结局。相反，仅在西班牙裔/拉丁裔早发性患者中，TGF-β通路未发生改变与改善预后存在特异性关联。结论：这些发现共同表明，WNT和TGF-β通路在不同种族的早发性结直肠癌患者中可能发挥不同作用，为开发针对性疗法以降低癌症健康差异奠定了基础。
肿瘤(癌症)患者之家