Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
Gut. 2018 Sep;67(9):1646-1651. doi: 10.1136/gutjnl-2016-313157. Epub 2017 Aug 16.
Colorectal cancers are the third most common cancers in women and men in the USA. While dietary and lifestyle factors such as Western diet, physical inactivity and obesity have been linked to an increased risk of this malignancy, the mechanisms for these associations are unclear. GI hormones, including ghrelin, are involved in energy balance by mediating appetite and metabolism; however, the association between ghrelin and colorectal cancer has not been studied.
We conducted a case-control study nested within the all-male Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish smokers (aged 50-69 years) to examine serum ghrelin concentration and colorectal cancer risk. Data from 284 colon and 239 rectal cancers and 523 controls (matched on age, date of blood draw and serum availability) were analysed. ORs and 95% CIs were calculated using multivariable (conditional) logistic regression.
Overall, low-serum ghrelin was significantly associated with increased risk of colorectal cancer (Q1 vs Q4: OR:1.57, 95% CI 1.05 to 2.34). For individuals developing tumours within 10 years of blood draw, those in the lowest quartile of serum ghrelin concentrations were statistically significantly more likely to develop colorectal cancers than those with higher serum ghrelin concentrations (OR: 10.86, 95% CI 5.01 to 23.55). However, for individuals with tumours developing more than 20 years after blood draw, low-serum ghrelin concentrations were associated with a decreased risk of colorectal cancer relative to those with the highest serum ghrelin concentrations (OR: 0.26, 95% CI 0.11 to 0.64).
Low-serum ghrelin was associated with an increased colorectal cancer risk within 10 years of blood draw with a decreased risk for developing colorectal cancer more than 20 years after blood draw. These results suggest that ghrelin concentrations may vary across the carcinogenic process.
在美国，结直肠癌是男性和女性中第三常见的癌症。虽然饮食和生活方式因素，如西方饮食、身体活动不足和肥胖，与这种恶性肿瘤的风险增加有关，但这些关联的机制尚不清楚。胃肠道激素，包括胃饥饿素，通过调节食欲和新陈代谢参与能量平衡；然而，胃饥饿素与结直肠癌之间的关系尚未得到研究。
我们在芬兰吸烟者的全男性α-生育酚、β-胡萝卜素癌症预防研究（年龄在 50-69 岁之间）中进行了一项病例对照研究，以研究血清胃饥饿素浓度与结直肠癌风险之间的关系。对 284 例结肠癌和 239 例直肠癌以及 523 例对照者（按年龄、采血日期和血清可获得性匹配）的数据进行了分析。使用多变量（条件）逻辑回归计算比值比（OR）和 95%置信区间（CI）。
总体而言，低血清胃饥饿素与结直肠癌风险增加显著相关（Q1 与 Q4：OR：1.57，95%CI 1.05-2.34）。对于在采血后 10 年内发生肿瘤的个体，血清胃饥饿素浓度最低的 quartile 发生结直肠癌的可能性明显高于血清胃饥饿素浓度较高的 quartile（OR：10.86，95%CI 5.01-23.55）。然而，对于在采血后 20 年以上发生肿瘤的个体，低血清胃饥饿素浓度与发生结直肠癌的风险降低相关，与血清胃饥饿素浓度最高的个体相比（OR：0.26，95%CI 0.11-0.64）。
采血后 10 年内，低血清胃饥饿素与结直肠癌风险增加相关，采血后 20 年以上发生结直肠癌的风险降低。这些结果表明，胃饥饿素浓度可能在致癌过程中发生变化。
