Carethers John M, Murali Bhavya, Yang Bing, Doctolero Ryan T, Tajima Akihiro, Basa Ranor, Smith E Julieta, Lee Monte, Janke Ryan, Ngo Tina, Tejada Ruth, Ji Ming, Kinseth Matthew, Cabrera Betty L, Miyai Katsumi, Keku Temitope O, Martin Christopher F, Galanko Joseph A, Sandler Robert S, McGuire Kathleen L
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Medicine, University of California San Diego, San Diego, California, United States of America; Moores Cancer Center, University of California San Diego, San Diego, California, United States of America.
Department of Biology, Molecular Biology Institute, San Diego State University, San Diego, California, United States of America.
PLoS One. 2014 Jun 23;9(6):e100461. doi: 10.1371/journal.pone.0100461. eCollection 2014.
African American patients with colorectal cancer show higher mortality than their Caucasian counterparts. Biology might play a partial role, and prior studies suggest a higher prevalence for microsatellite instability (MSI) among cancers from African Americans, albeit patients with MSI cancers have improved survival over patients with non-MSI cancers, counter to the outcome observed for African American patients. CD8+ T cell infiltration of colon cancer is postively correlated with MSI tumors, and is also related to improved outcome. Here, we utilized a 503-person, population-based colon cancer cohort comprising 45% African Americans to determine, under blinded conditions from all epidemiological data, the prevalence of MSI and associated CD8+ T cell infiltration within the cancers. Among Caucasian cancers, 14% were MSI, whereas African American cancers demonstrated 7% MSI (P = 0.009). Clinically, MSI cancers between races were similar; among microsatellite stable cancers, African American patients were younger, female, and with proximal cancers. CD8+ T cells were higher in MSI cancers (88.0 vs 30.4/hpf, P<0.0001), but was not different between races. Utilizing this population-based cohort, African American cancers show half the MSI prevalence of Caucasians without change in CD8+ T cell infiltration which may contribute towards their higher mortality from colon cancer.
患有结直肠癌的非裔美国患者的死亡率高于白人患者。生物学因素可能起到了一定作用，先前的研究表明，非裔美国人患癌的微卫星不稳定性（MSI）患病率较高，尽管MSI癌症患者的生存率高于非MSI癌症患者，这与非裔美国患者的观察结果相反。结肠癌中的CD8 + T细胞浸润与MSI肿瘤呈正相关，并且也与较好的预后相关。在这里，我们利用了一个基于人群的包含503人的结肠癌队列，其中45%为非裔美国人，在对所有流行病学数据不知情的情况下，确定癌症中MSI的患病率以及相关的CD8 + T细胞浸润情况。在白人癌症患者中，14%为MSI，而非裔美国癌症患者中MSI的比例为7%（P = 0.009）。临床上，不同种族间的MSI癌症情况相似；在微卫星稳定的癌症中，非裔美国患者更年轻，多为女性，且患近端癌症。MSI癌症中的CD8 + T细胞水平更高（88.0对30.4/hpf，P<0.0001），但不同种族之间并无差异。利用这个基于人群的队列研究发现，非裔美国癌症患者的MSI患病率仅为白人的一半，而CD8 + T细胞浸润没有变化，这可能是导致他们结肠癌死亡率较高的原因。
