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Abstract：
CYP2A6 is a polymorphic enzyme that inactivates nicotine; structural variants (SVs) include gene deletions and hybrids with the neighboring pseudogene CYP2A7. Two studies found that CYP2A7 deletions were associated with ovarian cancer risk. Using their methodology, we aimed to characterize CYP2A6 SVs (which may be misidentified by prediction software as CYP2A7 SVs), then assess CYP2A6 SV-associated risk for ovarian cancer, and extend analyses to lung cancer. An updated reference panel was created to impute CYP2A6 SVs from UK Biobank array data. Logistic regression models analyzed the association between CYP2A6 SVs and cancer risk, adjusting for covariates. Software-predicted CYP2A7 deletions were concordant with known CYP2A6 SVs. Deleterious CYP2A6 SVs were not associated with ovarian cancer (OR = 1.06; 95% CI: 0.80-1.37; p = 0.7) but did reduce the risk of lung cancer (OR = 0.44; 95% CI: 0.29-0.64; p < 0.0001), and a lung cancer subtype. Replication of known lung cancer associations indicates the validity of array-based SV analyses.
摘要：
CYP2A6是一种多态酶，可使尼古丁失活；结构变体（SV）包括基因缺失和与相邻假基因CYP2A7的杂交。两项研究发现CYP2A7缺失与卵巢癌风险相关。使用他们的方法，我们的目的是表征CYP2A6SV（可能被预测软件错误识别为CYP2A7SV），然后评估CYP2A6SV与卵巢癌相关的风险，并将分析扩展到肺癌。创建了更新的参考面板以从UKBiobank阵列数据估算CYP2A6SV。Logistic回归模型分析了CYP2A6SVs与癌症风险之间的关系，调整协变量。软件预测的CYP2A7缺失与已知的CYP2A6SV一致。有害的CYP2A6SV与卵巢癌无关（OR=1.06；95％CI：0.80-1.37；p=0.7），但确实降低了肺癌的风险（OR=0.44；95％CI：0.29-0.64；p<0.0001），和肺癌亚型.已知肺癌关联的复制表明基于阵列的SV分析的有效性。
