Krajinovic M, Labuda D, Richer C, Karimi S, Sinnett D
Service d'Hématologie-Oncologie, Centre de Cancérologie Charles-Bruneau et Centre de Recherche, Hôpital Sainte-Justine, Département de Pédiatrie, Université de Montréal, Montréal, Quebec, Canada.
Blood. 1999 Mar 1;93(5):1496-501.
Although acute lymphoblastic leukemia (ALL) is the most common childhood cancer, factors governing susceptibility to this disease have not yet been identified. As such, ALL offers a useful opportunity to examine the glutathione S-transferase and cytochrome P450 genes in determining susceptibility to pediatric cancers. Both enzymes are involved in carcinogen metabolism and have been shown to influence the risk a variety of solid tumors in adults. To determine whether these genes played a similar role in childhood leukemogenesis, we compared the allele frequencies of 177 childhood ALL patients and 304 controls for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French population of Quebec as our study population because of its relative genetic homogeneity. The GSTM1 null and CYP1A12A genotypes were both found to be significant predictors of ALL risk (odds ratio [OR] = 1.8). Those possessing both genotypes were at an even greater risk of developing the disease (OR = 3.3). None of the other alleles tested for proved to be significant indicators of ALL risk. Unexpectedly, girls carrying the CYP1A14 were significantly underrepresented in the ALL group (OR = 0.2), suggesting that a gender-specific protective role exists for this allele. These results suggest that the risk of ALL may indeed be associated with xenobiotics-metabolism, and thus with environmental exposures. Our findings may also explain, in part, why ALL is more prevalent among males than females.
尽管急性淋巴细胞白血病（ALL）是儿童期最常见的癌症，但尚未确定导致这种疾病易感性的因素。因此，ALL为研究谷胱甘肽S-转移酶和细胞色素P450基因在确定儿童癌症易感性方面提供了一个有用的机会。这两种酶都参与致癌物代谢，并已被证明会影响成年人患多种实体瘤的风险。为了确定这些基因在儿童白血病发生过程中是否起类似作用，我们比较了177例儿童ALL患者和304例对照的CYP1A1、CYP2D6、GSTM1和GSTT1基因的等位基因频率。由于魁北克的法国人群具有相对的基因同质性，我们选择其作为研究对象。结果发现，GSTM1基因缺失和CYP1A12A基因型均是ALL风险的重要预测指标（优势比[OR]=1.8）。同时拥有这两种基因型的个体患ALL的风险更高（OR=3.3）。其他检测的等位基因均未被证明是ALL风险的重要指标。出乎意料的是，携带CYP1A14的女孩在ALL组中的比例显著偏低（OR=0.2），这表明该等位基因存在性别特异性的保护作用。这些结果表明，ALL的风险可能确实与外源性物质代谢有关，进而与环境暴露有关。我们的研究结果也可能部分解释了为什么ALL在男性中比在女性中更普遍。
