Ruan Lian-Cheng, Zhang Yang, Su Lang, Zhu Ling-Xiao, Wang Si-Lin, Guo Qiang, Wan Bin-Gen, Qiu Sheng-Yu, Hu Sheng, Wei Yi-Ping, Zheng Qiao-Ling
Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, Jiangxi Province, China.
Nanchang Medical College, Nanchang 330004, Jiangxi Province, China.
World J Gastrointest Oncol. 2024 Jul 15;16(7):3055-3068. doi: 10.4251/wjgo.v16.i7.3055.
Few studies have investigated the association between gestational age, birth weight, and esophageal cancer risk; however, causality remains debated. We aimed to establish causal links between genetic gestational age and birth weight traits and gastroesophageal reflux disease (GERD), Barrett's esophagus (BE), and esophageal adenocarcinoma (EA). Additionally, we explored if known risk factors mediate these links.
To analyze of the relationship between gestational age, birth weight and GERD, BE, and EA.
Genetic data on gestational age and birth weight ( = 84689 and 143677) from the Early Growth Genetics Consortium and outcomes for GERD ( = 467253), BE ( = 56429), and EA ( = 21271) from genome-wide association study served as instrumental variables. Mendelian randomization (MR) and mediation analyses were conducted using MR-Egger, weighted median, and inverse variance weighted methods. Robustness was ensured through heterogeneity, pleiotropy tests, and sensitivity analyses.
Birth weight was negatively correlated with GERD and BE risk [odds ratio (OR) = 0.78; 95% confidence interval (CI): 0.69-0.8] and (OR = 0.75; 95%CI: 0.60-0.9), respectively, with no significant association with EA. No causal link was found between gestational age and outcomes. Birth weight was positively correlated with five risk factors: Educational attainment (OR = 1.15; 95%CI: 1.01-1.31), body mass index (OR = 1.06; 95%CI: 1.02-1.1), height (OR = 1.12; 95%CI: 1.06-1.19), weight (OR = 1.13; 95%CI: 1.10-1.1), and alcoholic drinks per week (OR = 1.03; 95%CI: 1.00-1.06). Mediation analysis showed educational attainment and height mediated the birth weight-BE link by 13.99% and 5.46%.
Our study supports the protective role of genetically predicted birth weight against GERD, BE, and EA, independent of gestational age and partially mediated by educational attainment and height.
很少有研究调查胎龄、出生体重与食管癌风险之间的关联；然而，因果关系仍存在争议。我们旨在建立遗传胎龄和出生体重特征与胃食管反流病（GERD）、巴雷特食管（BE）和食管腺癌（EA）之间的因果联系。此外，我们还探讨了已知风险因素是否介导了这些联系。
分析胎龄、出生体重与GERD、BE和EA之间的关系。
早期生长遗传学联盟提供的胎龄和出生体重的遗传数据（分别为84689例和143677例）以及全基因组关联研究中GERD（467253例）、BE（56429例）和EA（21271例）的结局数据用作工具变量。使用MR-Egger、加权中位数和逆方差加权方法进行孟德尔随机化（MR）和中介分析。通过异质性、多效性检验和敏感性分析确保稳健性。
出生体重与GERD和BE风险呈负相关[比值比（OR）分别为0.78；95%置信区间（CI）：0.69 - 0.8]和（OR = 0.75；95%CI：0.60 - 0.9），与EA无显著关联。未发现胎龄与结局之间存在因果联系。出生体重与五个风险因素呈正相关：受教育程度（OR = 1.15；95%CI：1.01 - 1.31）、体重指数（OR = 1.06；95%CI：1.02 - 1.1）、身高（OR = 1.12；95%CI：1.06 - 1.19）、体重（OR = 1.13；95%CI：1.10 - 1.1）以及每周饮酒量（OR = 1.03；95%CI：1.00 - 1.06）。中介分析表明，受教育程度和身高分别介导了出生体重与BE之间联系的13.99%和5.46%。
我们的研究支持遗传预测的出生体重对GERD、BE和EA具有保护作用，独立于胎龄，且部分由受教育程度和身高介导。
