PO.CL09.04 · 临床研究
黑色素瘤中遗传风险、社会经济地位和生活方式因素的独立效应：一项大规模基因-环境分析
Independent effects of genetic risk, socioeconomic status, and lifestyle factors in melanoma: A large-scale gene-environment analysis
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摘要 Abstract
中文摘要
背景：黑色素瘤是第5位最常见的癌症，且在年轻人群中发病率上升。既往文献显示黑色素瘤发病率反常地随着社会经济富裕程度而增加。然而，这一模式背后的机制仍不清楚。既往的基因-环境研究主要聚焦于日晒暴露和表型特征，而社会经济背景在很大程度上尚未被探索。我们的研究整合了来自英国生物样本库（UKBB）的遗传、社会经济和生活方式数据，以厘清遗传风险和社会经济因素对黑色素瘤发病率的独立及联合效应。
方法：我们分析了303,880名UKBB参与者，采用Cox比例风险模型估算无亲缘关系的白人英国血统人群中黑色素瘤发病的风险比（HR）和95%置信区间（CI）。我们对性别、体重指数、吸烟、肤色、饮酒频率、维生素D水平、防晒行为和评估中心（作为居住地的替代指标）进行了校正。我们按四分位数对多重剥夺指数（IMD）以及多基因风险评分（PRS）对黑色素瘤发病的效应进行建模：IMD和PRS各自独立、加性模型（IMD + PRS），以及交互模型（IMD × PRS）。
结果：在仅IMD模型中，与剥夺程度最低者（Q1）相比，Q3和Q4的参与者黑色素瘤发病风险显著更低（Q3：HR = 0.84 [95% CI = 0.72 - 0.98]；Q4：HR = 0.84，[95% CI = 0.71 - 1.00]）。在仅PRS模型中，PRS每增加一个单位与黑色素瘤风险增加2.16倍相关（HR = 2.16 [95% CI = 1.99 - 2.34]）。在加性模型中，PRS和IMD的效应基本保持不变。交互模型未显示IMD-PRS交互作用的证据（HR 1.0；p > 0.6）。
结论：更高的遗传易感性和更高的社会经济地位通过独立且不相互作用的途径与黑色素瘤风险增加相关。即使在考虑生活方式因素后，社会经济差异仍然存在，提示黑色素瘤风险受到超越个体生活方式和行为的因素塑造。我们的发现强调，没有证据表明社会经济差异反映了遗传易感性的差异，这强化了同时应对遗传风险和社会及结构性背景的预防和早期检测策略的必要性。
查看英文原文 English abstract
Background: Melanoma is the 5th most common cancer with an increasing incidence in the younger population. Prior literatures have shown that melanoma incidence paradoxically increases with socioeconomic affluence. Yet, the mechanisms underlying this pattern remains unclear. Prior gene-environment studies have focused primarily on sun exposure and phenotypic traits, with socioeconomic context largely unexplored. Our study integrates genetic, socioeconomic, and lifestyle data from the United Kingdom Biobank (UKBB) to disentangle the independent and joint effects of genetic risk and socioeconomic factors on melanoma incidence.
Methods: We analyzed 303,880 UKBB participants using Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident melanoma in an unrelated White British ancestry. We adjusted for sex, body mass index, smoking, skin color, alcohol intake frequency, vitamin D levels, sun-protection behavior, and assessment center (proxy for home location). We modelled the effects of the Index of Multiple Deprivation (IMD) by quartiles and polygenic risk score (PRS) on incident melanoma: IMD and PRS independently, additive model (IMD + PRS), and an interaction model (IMD × PRS).
Results: In the IMD-only model, compared to the least deprived (Q1), participants in Q3 and Q4 had significantly lower risk of melanoma incidence (Q3: HR = 0.84 [95% CI = 0.72 - 0.98]; Q4: HR = 0.84, [95% CI = 0.71 - 1.00]). In the PRS-only model, each unit increase in PRS was associated with a 2.16-fold increased melanoma risk (HR = 2.16 [95% CI = 1.99 - 2.34]). In the additive model, PRS and IMD effect remained largely unchanged. The interaction model showed no evidence of IMD-PRS interaction (HR 1.0; p > 0.6).
Conclusions: Greater genetic susceptibility and higher socioeconomic status was associated with increased melanoma risk through independent and non-interacting pathways. Even after accounting for lifestyle factors, socioeconomic differences remained, suggesting that melanoma risk is shaped by factors extending beyond individual lifestyle and behavior. Our findings highlight that there is no evidence that socioeconomic disparities reflect differences in genetic susceptibility, reinforcing the need for prevention and early detection strategies that address both inherited risk and social and structural contexts.
利益披露 Disclosure
E. Kim, None.