Int J Cancer:色素痣的数量与癌症风险有关吗?

2022-03-16 医路坦克 MedSci原创

许多流行病学研究报道较高的痣数量与癌症之间的正相关关系。但这种关联的确切性目前尚不清楚。本文使用生殖系遗传变异来检测这种表型特征是否是癌症的风险标记物。

     黑素细胞痣是由黑色素形成细胞的局部过度生长组成的良性皮肤肿瘤。痣的发展倾向是由遗传决定的,尽管儿童时期的阳光照射显然起了作用。 NEVI是黑色素瘤最强的表型危险因素,它们也与基底细胞癌(BCC)相关,但与鳞状细胞癌(SCC)无关。

    几项大型队列研究报道了较高的痣数量与包括乳腺癌和甲状腺在内的癌症之间的正相关性。最近有研究发现,痣数量与内科癌症总体上存在一定的相关性(15个或更多痣的HR与无痣相比=1.19;95%CI:1.05-1.35).观察到阳性但无显着相关性痣计数与几种类型的癌症之间,尽管两者都存在异质性整个队列的影响大小和方向。已经提出了几种机制来解释这些观察结果,包括丝裂原活化蛋白激酶(MAPK)信号传导途径或细胞周期蛋白依赖性激酶抑制剂2A(CDKN2A)中的常见突变,以及导致端粒长度维持(和增加)的共有途径。但是这些机制都是是推测性的,并无具体的实验证明。

    尽管有假设将痣和其他癌症联系在一起,但观察性研究报告的痣和癌症之间的联系是否代表了真实的关系,或者是由于与痣计数和癌症相关的因素(例如,临床监测)的偏见或混淆所致,目前仍不清楚。全基因组关联研究已经成功地确定了许多基因组区域,包括CDKN2A和磷脂酶A2组VI(PLA2G6)的变异。与表型显著相关的遗传变异为评估该表型和疾病结果之间的关系提供了机会。因此,我们试图使用种系遗传变异来检测这种表型特征是否是癌症的风险标记物。我们的研究样本来自两个种族背景相似但环境阳光水平不同的人群(英国和澳大利亚昆士兰)。

   我们使用英国生物库(n=394306)和QSkin队列(n=17427)中的个体水平数据计算了痣计数的多基因风险分数(PR)。对年龄、性别和前五个主成分的影响进行了Logistic回归分析,评估了痣、PR和每个肿瘤部位之间的相关性。在两个队列中,那些位于最高四分位数的雀斑痣患者比那些位于最低四分位数的患者患黑色素瘤的风险更高(英国生物库优势比[OR]1.42,95%可信区间[CI]:1.29-1.55;QSkin OR 1.58,95%CI:1.29-1.94)。我们还观察到基底细胞癌(BCC)和鳞状细胞癌(SCC)的风险增加,并伴随着较高的PRS痣(BCC UK Biobank OR 1.38,95%CI:1.33-1.44;QSkin UK Biobank OR 1.20,95%CI:1.05-1.38;SCC UK Biobank OR 1.41,95%CI:1.28-1.55;QSkin OR 1.44,95%CI:1.19-1.77)。

表1 英国Biobank和QSkin队列中的癌症病例数量及其患病率

 

图1  利用英国生物库中的个体水平数据,根据痣计数的四分位数,多基因风险得分(PRS),在基因预测的痣计数与个体或整体癌症风险之间的关联。任何癌症都不包括皮肤癌;血液病包括白血病和淋巴瘤;头颈部不包括唇癌;基底细胞癌;鳞状细胞癌,皮肤鳞状细胞癌

图2  根据痣计数四分位数多基因风险评分(PRS),使用QSkin队列中的个体水平数据,遗传预测的痣计数与个体或总体癌症风险之间的关联。任何癌症都不包括皮肤癌;血液癌症包括白血病和淋巴瘤;头颈部不包括唇癌;BCC,基底细胞癌;SCC,皮肤鳞状细胞癌

总而言之,我们发现痣的高遗传风险与皮肤癌之间有显著的相关性,但没有证据表明高遗传风险的痣与癌症的风险之间存在关联。我们推断,早期观察性研究中所报道的雀斑计数与癌症之间的联系不太可能是因果关系。

文献来源:Dusingize JC,  Law MH,  Pandeya N, Genetically determined cutaneous nevi and risk of cancer.Int J Cancer 2022 03 15;150(6)

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    2022-04-03 sunylz
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    2022-09-05 小小医者

    #色素痣#的数量与#癌症风险#,这些关联,特别有意思

    0

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    2022-03-20 ms1000001892479970

    学习

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    2022-03-18 ms3000001773438533

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    2022-03-17 ms7000001031705413

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    2022-03-16 屋顶瞄爱赏月

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    2022-03-16 yese

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