Gupta Kush, George Anthony, Attwood Kristopher, Gupta Ashish, Roy Arya Mariam, Gandhi Shipra, Siromoni Beas, Singh Anurag, Repasky Elizabeth, Mukherjee Sarbajit
Department of Internal Medicine, Umass Chan Medical School-Baystate, Springfield, MA 01199, USA.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancers (Basel). 2023 Dec 22;16(1):74. doi: 10.3390/cancers16010074.
Cold stress suppresses antitumor response in animal models, leading to tumor growth. Recent studies have also shown a negative correlation between the average annual temperature (AAT) and cancer incidence. We hypothesized that esophageal cancer (EC) and gastric cancer (GC) patients living in warmer climates have improved survival outcomes than those living in colder climates.
We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database from 1996 to 2015. We retrieved the National Centers for Environmental Information data to calculate the county-level AAT. Cox multivariate regression models were performed to measure the association between temperature (measured continuously at diagnosis and in 5-degree increments) and OS/DSS, adjusting for variables. All associations were compared at a significance level of 0.05. The OS and DSS were summarized using Kaplan-Meier methods. All statistics were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA).
A total of 17,408 EC patients were analyzed. The average age of the cohort was 65 years, 79% of which were males and 21% were females. Of them, 61.6% had adenocarcinoma, and 37.6% were squamous. After adjusting for covariates, patients in regions with an AAT > 53.5 °F had an 11% improvement in OS [HR 0.89 (95% CI 0.86-0.92), < 0.0001] and 13% in DSS [HR 0.87 (95% CI 0.84-0.90), < 0.0001]. When the temperature was analyzed in 5 °F increments, with each increment, there was a 3% improvement in OS [HR 0.97 (95% CI 0.96-0.98), < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.95-0.97), < 0.0001]. Subgroup analysis of squamous and adenocarcinoma showed similar results. These findings were validated in 20,553 GC patients. After adjusting for covariates, patients in regions with an AAT > 53.5 had a 13% improvement in OS [HR 0.87 (95% CI 0.85-0.90), < 0.0001] and 14% in DSS [HR 0.86 (95% CI 0.83-0.89), < 0.0001]. When analyzed in 5 °F increments, with each increment, there was a 4% improvement in OS [HR 0.96 (95% CI 0.952-0.971), < 0.0001] and 4% in DSS [HR 0.96 (95% CI 0.945-0.965), < 0.0001].
We showed for the first time that higher environmental temperatures are associated with significant improvements in OS and DSS in patients with gastro-esophageal cancers, notwithstanding the limitations of a retrospective database analysis. Further confirmatory and mechanistic studies are required to implement specific interventional strategies.
在动物模型中,冷应激会抑制抗肿瘤反应,导致肿瘤生长。最近的研究还表明,年平均气温(AAT)与癌症发病率之间存在负相关。我们假设,生活在气候较温暖地区的食管癌(EC)和胃癌(GC)患者比生活在寒冷地区的患者生存结果更好。
我们使用1996年至2015年的监测、流行病学和最终结果(SEER)数据库进行了一项回顾性分析。我们检索了美国国家环境信息中心的数据,以计算县级AAT。采用Cox多变量回归模型来衡量温度(在诊断时连续测量,并以5度为增量)与总生存期(OS)/疾病特异性生存期(DSS)之间的关联,并对变量进行调整。所有关联均在0.05的显著性水平上进行比较。OS和DSS采用Kaplan-Meier方法进行总结。所有统计分析均使用SAS 9.4版本(SAS Institute Inc.,美国北卡罗来纳州卡里)进行。
共分析了17408例EC患者。该队列的平均年龄为65岁,其中79%为男性,21%为女性。其中,61.6%患有腺癌,37.6%为鳞状细胞癌。在调整协变量后,AAT>53.5°F地区的患者OS改善了11%[风险比(HR)0.89(95%置信区间0.86-0.92),P<0.0001],DSS改善了13%[HR 0.87(95%置信区间0.84-0.90),P<0.0001]。当以5°F为增量分析温度时,每增加一度,OS改善3%[HR 0.97(95%置信区间0.96-0.98),P<0.0001],DSS改善4%[HR 0.96(95%置信区间0.95-0.97),P<0.0001]。鳞状细胞癌和腺癌的亚组分析显示了相似的结果。这些发现在20553例GC患者中得到了验证。在调整协变量后,AAT>53.5地区的患者OS改善了13%[HR 0.87(95%置信区间0.85-0.90),P<0.0001],DSS改善了14%[HR 0.86(95%置信区间0.83-0.89),P<0.0001]。当以5°F为增量分析时,每增加一度,OS改善4%[HR 0.96(95%置信区间0.952-0.971),P<0.0001],DSS改善4%[HR 0.96(95%置信区间0.945-0.965),P<0.0001]。
我们首次表明,尽管回顾性数据库分析存在局限性,但较高的环境温度与胃食管癌患者的OS和DSS显著改善相关。需要进一步的验证性研究和机制研究来实施具体的干预策略。