Sobti R C, Sharma S, Joshi A, Jindal S K, Janmeja A
Department of Biotechnology, Panjab University, Chandigarh, India.
Biomarkers. 2003 Sep-Oct;8(5):415-28. doi: 10.1080/13547500310001619860.
This case-control study was conducted to examine the association between the CYP1A1 and CYP2D6 genotypes and lung cancer risk among North Indians. The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone. With regard to the metabolism of debrisoquine, no poor metabolizers were found amongst the subjects. The odds ratio of risk with the heterozygous extensive metabolizer (HEM) genotype was 1.5. However, in the presence of at least a single copy of the variant CYP1A1 MspI allele and the CYP2D6 HEM genotype, the risk was two-fold for squamous cell carcinoma (SQCC). When the CYP1A1 Val/Val and CYP2D6 HEM genotypes were taken together, the risk for SCLC was four-fold. Stratified analysis indicated an interaction between bidi smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. Heavy smokers (Brinkman index>400) with Val/Val genotypes were at a very high risk of developing lung cancer (odds ratio 29.30, 95% confidence interval 2.42-355, p=0.008). Heavy smokers with CYP1A1 MspI (CYP1A11/2A or CYP1A12A/*2A) genotype had a seven-fold risk for SCLC compared with non-smokers. This study is the first to be carried out on a North Indian population, and, although small, suggests that CYP1A1 and CYP2D6 polymorphisms might have a role in determining the risk for lung cancer and should be investigated further.
本病例对照研究旨在探讨北印度人群中CYP1A1和CYP2D6基因多态性与肺癌风险之间的关联。与CYP1A1 Val/Val等位基因相关的肺癌估计相对风险为2.68，若仅考虑小细胞肺癌（SCLC）病例，则该风险为四倍。关于异喹胍的代谢，在研究对象中未发现慢代谢者。杂合子广泛代谢者（HEM）基因型的风险优势比为1.5。然而，在存在至少一个拷贝的CYP1A1 MspI变异等位基因和CYP2D6 HEM基因型的情况下，鳞状细胞癌（SQCC）的风险为两倍。当CYP1A1 Val/Val和CYP2D6 HEM基因型同时存在时，SCLC的风险为四倍。分层分析表明，双向吸烟与CYP1A1变异基因型之间存在交互作用，影响SQCC和SCLC的风险。携带Val/Val基因型的重度吸烟者（Brinkman指数>400）患肺癌的风险非常高（优势比29.30，95%置信区间2.42 - 355，p = 0.008）。与非吸烟者相比，携带CYP1A1 MspI（CYP1A11/2A或CYP1A12A/*2A）基因型的重度吸烟者患SCLC的风险高七倍。本研究首次在北印度人群中开展，尽管样本量较小，但表明CYP1A1和CYP2D6基因多态性可能在确定肺癌风险中发挥作用，应进一步开展研究。
