Naudin Sabine, Wang Molin, Dimou Niki, Ebrahimi Elmira, Genkinger Jeanine, Adami Hans-Olov, Albanes Demetrius, Babic Ana, Barnett Matt, Bogumil David, Cai Hui, Chen Chu, Eliassen A Heather, Freudenheim Jo L, Gierach Gretchen, Giovannucci Edward L, Gunter Marc J, Håkansson Niclas, Hirabayashi Mayo, Hou Tao, Huang Brian Z, Huang Wen-Yi, Jayasekara Harindra, Jones Michael E, Katzke Verena A, Koh Woon-Puay, Lacey James V, Lagerros Ylva Trolle, Larsson Susanna C, Liao Linda M, Lo Kenneth, Loftfield Erikka, MacInnis Robert J, Männistö Satu, McCullough Marjorie L, Miller Anthony, Milne Roger L, Moore Steven C, Mucci Lorelei A, Neuhouser Marian L, Patel Alpa V, Platz Elizabeth A, Prizment Anna, Robien Kim, Rohan Thomas E, Sacerdote Carlotta, Sandin Sven, Sawada Norie, Schoemaker Minouk, Shu Xiao-Ou, Sinha Rashmi, Snetselaar Linda, Stampfer Meir J, Stolzenberg-Solomon Rachael, Thomson Cynthia A, Tjønneland Anne, Um Caroline Y, van den Brandt Piet A, Visvanathan Kala, Wang Sophia S, Wang Renwei, Weiderpass Elisabete, Weinstein Stephanie J, White Emily, Willett Walter, Woslk Alicja, Wolpin Brian M, Yaun Shiaw-Shyuan S, Yuan Chen, Yuan Jian-Min, Zheng Wei, Brennan Paul, Smith-Warner Stephanie A, Ferrari Pietro
International Agency for Research on Cancer, World Health Organization, Lyon, France.
UPS, UVSQ, National Institute of Health and Medical Research, Gustave Roussy, Centre for research in epidemiology and population health, Villejuif, France.
PLoS Med. 2025 May 20;22(5):e1004590. doi: 10.1371/journal.pmed.1004590. eCollection 2025 May.
Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.
Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America. A total of 2,494,432 participants without cancer at baseline (62% women, 84% European ancestries, 70% alcohol drinkers [alcohol intake ≥ 0.1 g/day], 47% never smokers) were recruited between 1980 and 2013 at the median age of 57 years and 10,067 incident pancreatic cancer cases were recorded. In age- and sex-stratified Cox proportional hazards models adjusted for smoking history, diabetes status, body mass index, height, education, race and ethnicity, and physical activity, pancreatic cancer hazard ratios (HR) and 95% confidence intervals (CI) were estimated for categories of alcohol intake and in continuous for a 10 g/day increase. Potential heterogeneity by sex, smoking status, geographic regions, and type of alcoholic beverage was investigated. Alcohol intake was positively associated with pancreatic cancer risk, with HR30-to-<60 g/day and HR≥60 g/day equal to 1.12 (95% CI [1.03,1.21]) and 1.32 (95% CI [1.18,1.47]), respectively, compared to intake of 0.1 to <5 g/day. A 10 g/day increment of alcohol intake was associated with a 3% increased pancreatic cancer risk overall (HR: 1.03; 95% CI [1.02,1.04]; pvalue < 0.001) and among never smokers (HR: 1.03; 95% CI [1.01,1.06]; pvalue = 0.006), with no evidence of heterogeneity by sex (pheterogeneity = 0.274) or smoking status (pheterogeneity = 0.624). Associations were consistent in Europe-Australia (HR10 g/day = 1.03, 95% CI [1.00,1.05]; pvalue = 0.042) and North America (HR10 g/day = 1.03, 95% CI [1.02,1.05]; pvalue < 0.001), while no association was observed in cohorts from Asia (HR10 g/day = 1.00, 95% CI [0.96,1.03]; pvalue = 0.800; pheterogeneity = 0.003). Positive associations with pancreatic cancer risk were found for alcohol intake from beer (HR10 g/day = 1.02, 95% CI [1.00,1.04]; pvalue = 0.015) and spirits/liquor (HR10 g/day = 1.04, 95% CI [1.03,1.06]; pvalue < 0.001), but not wine (HR10 g/day = 1.00, 95% CI [0.98,1.03]; pvalue = 0.827). The differential associations across geographic regions and types of alcoholic beverages might reflect differences in drinking habits and deserve more investigations.
Findings from this large-scale pooled analysis support a modest positive association between alcohol intake and pancreatic cancer risk, irrespective of sex and smoking status. Associations were particularly evident for baseline alcohol intake of at least 15 g/day in women and 30 g/day in men.
酒精是一种已知的致癌物，但国际专家小组认为酒精与胰腺癌风险之间的关联证据有限或尚无定论。我们在一个大型前瞻性研究联盟中研究了酒精摄入量与胰腺癌风险之间的关联。
基于人群的个体水平数据来自四大洲的30个队列，包括亚洲、澳大利亚、欧洲和北美洲。在1980年至2013年期间，共招募了2494432名基线时无癌症的参与者（62%为女性，84%为欧洲血统，70%为饮酒者[酒精摄入量≥0.1克/天]，47%从不吸烟），中位年龄为57岁，记录了10067例胰腺癌新发病例。在根据吸烟史、糖尿病状态、体重指数、身高、教育程度、种族和民族以及体力活动进行调整的年龄和性别分层的Cox比例风险模型中，对酒精摄入量类别估计胰腺癌风险比（HR）和95%置信区间（CI），并对每天增加10克进行连续估计。研究了按性别、吸烟状态、地理区域和酒精饮料类型的潜在异质性。酒精摄入量与胰腺癌风险呈正相关，与每天摄入0.1至<5克相比，每天摄入30至<60克和≥60克的HR分别为1.12（95%CI[1.03,1.21]）和1.32（95%CI[1.18,1.47]）。每天酒精摄入量增加10克总体上与胰腺癌风险增加3%相关（HR：1.03；95%CI[1.02,1.04]；p值<0.001），在从不吸烟者中也是如此（HR：1.03；95%CI[1.01,1.06]；p值=0.006），没有证据表明按性别（p异质性=0.274）或吸烟状态（p异质性=0.624）存在异质性。在欧洲-澳大利亚（每天摄入10克的HR=1.03，95%CI[1.00,1.05]；p值=0.042）和北美洲（每天摄入10克的HR=1.03，95%CI[1.02,1.05]；p值<0.001），关联是一致的，而在亚洲队列中未观察到关联（每天摄入10克的HR=1.00，95%CI[0.96,1.03]；p值=0.800；p异质性=0.003）。发现啤酒（每天摄入10克的HR=1.02，95%CI[1.00,1.04]；p值=0.015）和烈酒/白酒（每天摄入10克的HR=1.04，95%CI[1.03,1.06]；p值<0.001）的酒精摄入量与胰腺癌风险呈正相关，但葡萄酒（每天摄入10克的HR=1.00，95%CI[0.98,1.03]；p值=0.827）则不然。地理区域和酒精饮料类型之间的差异关联可能反映了饮酒习惯的差异，值得进一步研究。
这项大规模汇总分析的结果支持酒精摄入量与胰腺癌风险之间存在适度的正相关，与性别和吸烟状态无关。对于女性基线酒精摄入量至少为15克/天和男性为30克/天，关联尤为明显。
