Magahis Patrick T, Cornet Nicole, Tang Laura, Arora Kanika, Hingorani Neha, King Stephanie, Markowitz Arnold J, Schattner Mark, Shimada Shoji, Maron Steven B, Vardhana Santosha, Lumish Melissa, Cercek Andrea, Janjigian Yelena Y, Coit Daniel, Mendelsohn Robin B, Berger Michael F, Strong Vivian E, Stadler Zsofia K, Laszkowska Monika
Weill Cornell Medical College of Cornell University, New York, New York, USA.
Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
Cancer Med. 2024 Dec;13(23):e70451. doi: 10.1002/cam4.70451.
There has been a paradoxical rise in young-onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self-reported race is also poorly characterized and may be unreliable as a proxy for genetic differences. We aimed to compare differences in histology and genetic ancestry between YOGC and average-onset gastric cancer (AOGC).
This retrospective cohort included all patients with GC at Memorial Sloan Kettering (MSK) from January 2013 to March 2021. Data on demographics, tumor characteristics, and precursor lesions were collected. Genetic ancestry was inferred from MSK-Integrated Mutation Profiling of Actionable Cancer Targets panel.
Of 1685 individuals with GC, 290 had YOGC. Compared to AOGC, individuals with YOGC tended to be female, Hispanic, foreign-born, and feature diffuse-type histology. YOGC was less likely to have precursor lesions, including intestinal metaplasia (20% vs. 37%, p < 0.01) and dysplasia (4% vs. 14%, p < 0.01). Of 560 patients with ancestry data, 127 had YOGC. Admixed, East Asian, and South Asian ancestries were more likely to present with YOGC while Europeans presented with AOGC. Intestinal metaplasia was enriched among East Asians, maintained when stratifying by histology and GC onset.
We observed YOGC was more common in East and South Asians, and while YOGC may be less likely to develop in the setting of precursor lesions these high-risk states may also be enriched in East Asians. Future research is needed to understand drivers behind such differences and outcome disparities given these individuals may be less amenable to endoscopic interventions.
年轻发病的胃癌（YOGC），即50岁前诊断出的胃癌，其发病率出现了反常上升。前驱病变可能参与发病机制，但其在进展为不同组织学亚型中的作用尚不清楚。自我报告的种族的影响也未得到充分描述，作为遗传差异的替代指标可能不可靠。我们旨在比较YOGC与平均发病年龄胃癌（AOGC）在组织学和遗传血统方面的差异。
这项回顾性队列研究纳入了2013年1月至2021年3月在纪念斯隆凯特琳癌症中心（MSK）诊断为胃癌的所有患者。收集了人口统计学、肿瘤特征和前驱病变的数据。通过MSK可操作癌症靶点综合突变分析推断遗传血统。
在1685例胃癌患者中，290例为YOGC。与AOGC相比，YOGC患者倾向于为女性、西班牙裔、外国出生，且具有弥漫型组织学特征。YOGC患者发生前驱病变的可能性较小，包括肠化生（20%对37%，p<0.01）和发育异常（4%对14%，p<0.01）。在560例有血统数据的患者中，127例为YOGC。混血、东亚和南亚血统更易出现YOGC，而欧洲血统则表现为AOGC。肠化生在东亚人群中更为富集，按组织学和胃癌发病年龄分层时保持这一特征。
我们观察到YOGC在东亚和南亚人群中更为常见，虽然YOGC在前驱病变情况下发生的可能性较小，但这些高危状态在东亚人群中也可能更为富集。鉴于这些个体可能不太适合内镜干预，未来需要开展研究以了解这些差异和结局差异背后的驱动因素。
