常见的遗传多态性导致慢性淋巴细胞白血病与非黑素瘤皮肤癌之间的关联。
Common genetic polymorphisms contribute to the association between chronic lymphocytic leukaemia and non-melanoma skin cancer.
机构信息
Service d'hématologie et Oncologie, Centre Hospitalier de Versailles, Le Chesnay; Université Paris-Saclay, UVSQ, Inserm, Équipe "Exposome et Hérédité", CESP, 94805, Villejuif, France.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
出版信息
Int J Epidemiol. 2021 Aug 30;50(4):1325-1334. doi: 10.1093/ije/dyab042.
BACKGROUND
Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.
METHODS
We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02-1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08-1.38, Ptrend = 1.36 × 10-5), which was driven by shared genetic susceptibility at the 6p25.3 locus.
CONCLUSION
These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.
背景
流行病学研究表明，慢性淋巴细胞白血病（CLL）与非黑色素瘤皮肤癌（NMSC）之间存在正相关关系。我们假设 CLL 和 NMSC 之间存在共同的遗传风险因素，这可能导致这些疾病之间的关联。
方法
我们通过对 3100 例 CLL 病例和 7667 例对照进行荟萃分析，研究了（i）已确定的 NMSC 易感性基因座与 CLL 风险之间的关系，以及（ii）在 4242 例基底细胞癌（BCC）病例、825 例鳞状细胞癌（SCC）病例和 12802 例对照中已确定的 CLL 基因座与 NMSC 风险之间的关系。使用已建立的基因座构建 CLL、BCC 和 SCC 的多基因风险评分（PRS）。使用逻辑回归估计比值比（OR）和 95%置信区间（CI）。
结果
较高的 CLL-PRS 与 BCC 风险增加相关（第 4 四分位与第 1 四分位相比，OR=1.13，95%CI：1.02-1.24，Ptrend=0.009），即使去除了共享的 6p25.3 基因座也是如此。未观察到 BCC-PRS 与 CLL 风险之间存在关联（Ptrend=0.68）。这些发现支持 CLL 对 BCC 风险的致病作用，但不支持 BCC 对 CLL 风险的致病作用。更高的 SCC-PRS 与更高的 CLL 风险相关（第 4 四分位与第 1 四分位相比，OR=1.22，95%CI：1.08-1.38，Ptrend=1.36×10-5），这是由 6p25.3 基因座的共享遗传易感性驱动的。
结论
这些发现突出了 CLL 和 NMSC 发病机制中多效性的作用，并表明单个多效性基因座 6p25.3 驱动了观察到的 SCC 遗传易感性与 CLL 风险增加之间的关联。该研究还提供了证据表明，CLL 的遗传易感性增加了 BCC 的风险。
Zotero 插件