瘦与非瘦人群中肝癌的生活方式因素和人群归因风险

StephenW

瘦与非瘦人群中肝癌的生活方式因素和人群归因风险

更多咖啡与美国组降低肝癌风险相关

EASL 国际肝脏大会 2022，伦敦，2022 年 6 月 22 日至 26 日

马克·马斯科里尼

在一个种族多样的 181,346 人美国队列中，每天喝 2 杯或更多杯咖啡可降低 30% 的肝细胞癌 (HCC) 风险 [1]。在瘦人中，每天喝 2 杯以上的爪哇咖啡可使 HCC 风险减半。这项针对加利福尼亚-夏威夷队列的研究还发现，肥胖会使 HCC 风险增加三分之二，而吸烟则使风险增加三倍。作者还发现，在这一人群中，通过消除 5 种风险因素，瘦人的 HCC 风险可能会降低 52%，而非瘦人的 HCC 风险可能会降低 37%。

南加州大学 (USC) 和夏威夷大学的研究人员指出，HCC 在癌症死亡原因中排名第三。他们说，随着酒精和非酒精相关肝病发病率的上升，识别和改变 HCC 风险因素变得越来越紧迫。观察性研究将几个可改变的风险因素与 HCC 的发展联系起来：吸烟、酒精、身体活动、饮食质量、咖啡和肥胖。

南加州大学/夏威夷的研究人员计划进行这项研究，以计算可改变生活方式 HCC 风险因素的个体和综合人群归因风险 (PAR)。 PAR 代表人群中消除风险因素可预防的 HCC 病例比例 [2]。他们还旨在比较瘦人（正常体重指数）与非瘦人（体重指数升高）的 PAR，因为这两组之间的生活方式因素可能不同。

这项前瞻性分析涉及多民族队列研究的人员，其中包括加利福尼亚和夏威夷的 215,000 多名 45 至 75 岁的男性和女性。随着 1993 年至 1996 年的队列进入，现在的随访时间延长了 20 年。当人们进入多民族队列研究时，他们完成了一份 26 页的问卷，其中包括定量饮食史（aMED 依从性评分）。截至 2017 年 12 月，研究人员将队列成员与加州和夏威夷的癌症登记处联系起来。他们通过组织学代码 C22.0 和形态学代码 8170-8175 确定了事件（新诊断）HCC。

一个针对年龄、性别、种族/民族、糖尿病和高血压进行调整的多变量 Cox 模型探索了整个人群以及瘦和非瘦参与者的每个生活方式因素与 HCC 之间的关联。对于非亚洲人来说，瘦意味着体重指数低于 25 kg/m2；对于亚洲人来说，瘦意味着体重指数低于 23.5 kg/m2。南加州大学/夏威夷团队基于以下对每个风险因素的二分法进行 PAR 比较：吸烟（当前与以前或从不）、饮酒（重度与中度或无）、身体活动（无与低到高）、饮食质量（最低[最差] 五分之一 vs 五分之一 2 至 5），咖啡摄入量（每天 0 或 1 杯 vs 2 杯或更多杯），肥胖（是 vs 否）。

研究人群包括 63,369 名瘦人（35%）和 117,977 名非瘦人（65%）。总体年龄平均为 60 岁，46% 的队列是男性，16% 的黑人，29% 的亚洲人，22% 的西班牙裔，25% 的白人和 7% 的夏威夷原住民。

169 名瘦人 (0.3%) 患上 HCC，而 684 名非瘦人 (0.6%) 被诊断出患有 HCC。事实证明，某些风险因素在被诊断患有 HCC 的人中比在没有 HCC 的人中更为普遍：以前或现在的吸烟者分别为 72.9% 和 56.1%；重度酒精使用 23.1% vs 14.8%；每天少于 2 杯咖啡 79.7% vs 75.6%；次优饮食质量 82.8% vs 78.1%。

多变量分析确定了与总体人群和/或瘦或非瘦人群中新诊断的 HCC 独立相关的六个因素，风险比 (HR)（和 95% 置信区间）：

前吸烟者 vs 从不：总体 HR 1.64（1.37 至 1.96）；精益 HR 2.08（1.40 至 3.09）；非精益 HR 1.55（1.26 至 1.89）
当前吸烟者与从不：总体 HR 2.96（2.40 至 3.67）；精益 HR 4.41（2.86 至 6.81）；非精益 HR 2.62（2.04 至 3.35）
重度酒精与无酒精：总体 HR 1.24（1.02 至 1.51）
饮食质量五分之一（最佳）与五分之一（最差）：总体 HR 0.69（0.54 至 0.88）；非精益 HR 0.61（0.46 至 0.80）
每天 2 杯或更多杯咖啡 vs 无：总体 HR 0.70（0.57 至 0.87）；精益 HR 0.47（0.29 到 0.77）；非精益 HR 0.77（0.50 至 0.98）
肥胖是与否：总体 HR 1.65（1.41 至 1.94）

PAR（如果风险因素消失则不会发展的 HCC 病例的比例）证明，低咖啡摄入量（21.3%）最高，其次是吸烟（15.1%）、肥胖（14.5%）、饮酒（7.1%）、体育锻炼（5.5%）和饮食质量（4.1%）。消除所有这些风险因素将阻止该人群中超过一半的新 HCC 诊断（51.9%）。
消除不喝咖啡对瘦人的 PAR 影响比非瘦人大得多（45.1% 对 14.8%）。同样的不平衡也适用于戒烟（瘦肉的 PAR 为 24.9%，非瘦肉的 PAR 为 12.3%）。避免所有分析的风险因素对瘦人的影响也比对非瘦人的影响更大（PAR 65.2% vs 37.4%）。

研究人员警告说，他们在这个种族多元化的加利福尼亚-夏威夷群体中的发现可能不适用于其他人群。此外，他们的分析缺乏关于一种关键 HCC 危险因素病毒性肝炎的数据。

考虑到这些限制，南加州大学/夏威夷团队得出结论，通过避免分析的所有生活方式风险因素，可以预防该人群中超过一半的新 HCC 病例。事实证明，每天喝 2 杯或更多杯咖啡对预防 HCC 的益处特别显着，尤其是在瘦人身上。研究人员强调，可改变的风险因素对瘦人（体重指数正常的人）的影响要大于非瘦人（超重和肥胖）的人。

参考
1. Zhou K、Lim T、Dodge JL 等。瘦与非瘦人群中肝癌的生活方式因素和人群归因风险。 EASL 国际肝脏大会 2022，伦敦，2022 年 6 月 22 日至 26 日。摘要 OS106。

StephenW

Lifestyle factors and population attributable risk of hepatocellular carcinoma in lean vs non-lean populations   

More Coffee Tied to Lower Liver Cancer Risk in US Group

EASL International Liver Congress 2022, London, June 22-26, 2022

Mark Mascolini

Drinking 2 or more cups of coffee daily cut risk of hepatocellular carcinoma (HCC) 30% in an ethnically diverse 181,346-person US cohort [1]. In lean people, downing more than 2 cups of java daily halved HCC risk. This study of a California-Hawaii cohort also found that obesity boosted HCC risk by two thirds, while smoking tripled the risk. Authors also found that in this population HCC risk might have ben prevented by 52% in lean people by eliminating the 5 risk factors and by 37% in non-lean people.

Researchers from the University of Southern California (USC) and the University of Hawaii noted that HCC ranks third in causes of cancer death. As incidence of alcohol- and nonalcohol-related liver disease rises, they said, identifying and modifying HCC risk factors gains urgency. Observational studies tie several modifiable risk factors to HCC development: smoking, alcohol, physical activity, diet quality, coffee, and obesity.

The USC/Hawaii investigators planned this study to figure individual and combined population-attributable risk (PAR) for modifiable lifestyle HCC risk factors. PARs represent the proportion of HCC cases that removing a risk factor may prevent in a population [2]. They also aimed to compare PAR in lean people (normal body mass index) versus nonlean people (elevated body mass index) because lifestyle factors can differ between those two groups.

This prospective analysis involved people in the Multiethnic Cohort Study, which includes more than 215,000 men and women 45 to 75 years old in California and Hawaii. With cohort entry in 1993-1996, follow-up now extends over 20 years. When people entered the Multiethnic Cohort Study they completed a 26-page questionnaire that included quantitative diet history (aMED adherence score). Researchers linked cohort members to statewide California and Hawaii cancer registries through December 2017. They identified incident (newly diagnosed) HCC by histology code C22.0 and morphology codes 8170-8175.

A multivariable Cox model adjusted for age, sex, race/ethnicity, diabetes, and hypertension explored associations between each lifestyle factor and HCC for the whole population and for lean and nonlean participants. For non-Asians lean meant a body mass index below 25 kg/m2; and for Asians lean meant a body mass index below 23.5 kg/m2. The USC/Hawaii team based PAR comparisons on the following dichotomies for each risk factor: smoking (current vs former or never), alcohol use (heavy vs moderate or none), physical activity (none vs low to high), diet quality (lowest [worst] quintile vs quintiles 2 to 5), coffee intake (0 or 1 vs 2 or more cups daily), obesity (yes vs no).

The study population included 63,369 lean people (35%) and 117,977 nonlean people (65%). Overall age averaged 60 years, 46% of the cohort were men, 16% black, 29% Asian, 22% Hispanic, 25% white, and 7% Native Hawaiian.

While HCC developed in 169 lean people (0.3%), HCC got diagnosed in 684 nonlean people (0.6%). Certain risk factors proved more prevalent in people diagnosed with HCC than in those who remained HCC-free: former or current smoker 72.9% vs 56.1%; heavy alcohol use 23.1% vs 14.8%; fewer than 2 cups of coffee daily 79.7% vs 75.6%; suboptimal diet quality 82.8% vs 78.1%.

Multivariable analysis identified six factors independently associated with newly diagnosed HCC in the overall population and/or in the lean or nonlean population at the following hazard ratios (HR) (and 95% confidence intervals):

Former smoker vs never: overall HR 1.64 (1.37 to 1.96); lean HR 2.08 (1.40 to 3.09); nonlean HR 1.55 (1.26 to 1.89)
Current smoker vs never: overall HR 2.96 (2.40 to 3.67); lean HR 4.41 (2.86 to 6.81); nonlean HR 2.62 (2.04 to 3.35)
Heavy alcohol vs none: overall HR 1.24 (1.02 to 1.51)
Diet quality quintile 5 (best) vs quintile 1 (worst): overall HR 0.69 (0.54 to 0.88); nonlean HR 0.61 (0.46 to 0.80)
2 or more cups of coffee daily vs none: overall HR 0.70 (0.57 to 0.87); lean HR 0.47 (0.29 to 0.77); nonlean HR 0.77 (0.50 to 0.98)
Obesity yes vs no: overall HR 1.65 (1.41 to 1.94)

PAR (proportion of HCC cases that would not develop if the risk factor disappeared) proved highest for low coffee intake (21.3%), followed by smoking (15.1%), obesity (14.5%), alcohol use (7.1%), physical activity (5.5%), and diet quality (4.1%). Eliminating ALL these risk factors would prevent more than half of new HCC diagnoses in this population (51.9%).

Eliminating abstaining from coffee had a much greater impact on PAR in lean people than nonlean people (45.1% vs 14.8%). The same imbalance held true for eliminating smoking (PAR 24.9% in lean and 12.3% in nonlean). Avoiding all analyzed risk factors also had a greater impact in lean people than in nonlean people (PAR 65.2% vs 37.4%).

The researchers cautioned that their findings in this ethnically diverse California-Hawaii group may not apply to other populations. Also, their analysis lacked data on one critical HCC risk factor, viral hepatitis.

With those limitations in mind, the USC/Hawaii team concluded that more than half of new HCC cases in this population might be prevented by avoiding all the lifestyle risk factors analyzed. The HCC-prevention benefit of drinking 2 or more cups of coffee daily proved particularly striking, especially in lean people. The researchers stressed that the contribution of modifiable risk factors to HCC risk was greater for lean people (those with normal body mass index) than for nonlean (overweight and obese) people.

References
1. Zhou K, Lim T, Dodge JL, et al. Lifestyle factors and population attributable risk of hepatocellular carcinoma in lean vs non-lean populations. EASL International Liver Congress 2022, London, June 22-26, 2022. Abstract OS106.