It has been hypothesised that nonsyndromic cleft lip/palate (nsCL/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL/P cases, but several genes (e.g., CDH1, AXIN2) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL/P and oral cavity/oropharyngeal cancers (OC/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL/P PRS and increased odds of OC/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13; p = .000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10; p = .55). Mendelian randomization analyses provided evidence that major nsCL/P risk variants are unlikely to influence OC/OPC. Our findings suggest possible shared genetic influences on nsCL/P and OC/OPC.

中文翻译：

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评估对非综合征性唇裂/腭裂和口咽肿瘤的共同遗传影响。


据推测，非综合征性唇裂/腭裂 (nsCL/P) 和癌症可能具有共同的病因学危险因素。人群研究发现 nsCL/P 病例中癌症发病率增加的证据不一致，但一些基因（例如CDH1 、 AXIN2 ）与两种表型的病因有关。我们的目的是评估 nsCL/P 和口腔/口咽癌 (OC/OPC) 之间共同的遗传病因学，它们影响相似的解剖区域。使用 5,048 个 OC/OPC 病例和 5,450 个欧洲血统对照的原始样本以及来自英国生物银行的 750 个病例和 336,319 个对照的复制样本，我们使用 nsCL/P 多基因风险评分 (PRS) 和孟德尔随机化分析来估计遗传重叠评估潜在的因果机制。在主要样本中，我们发现了强有力的证据表明 nsCL/P PRS 与 OC/OPC 几率增加之间存在关联（分数每增加一个标准差，优势比 [OR]：1.09；95% 置信区间 [CI]：1.04 ，1.13； p = .000053）。尽管置信区间与初步估计值重叠，但我们在英国生物银行中没有发现 PRS 和 OC/OPC 之间存在关联的确凿证据（OR 1.02；95% CI：0.95，1.10； p = .55）。孟德尔随机化分析提供的证据表明，主要 nsCL/P 风险变异不太可能影响 OC/OPC。我们的研究结果表明 nsCL/P 和 OC/OPC 可能存在共同的遗传影响。