Rossi Anna Maria, Hansteen Inger-Lise, Skjelbred Camilla Furu, Ballardin Michela, Maggini Valentina, Murgia Elena, Tomei Antonio, Viarengo Paolo, Knudsen Lisbeth E, Barale Roberto, Norppa Hannu, Bonassi Stefano
Department of Biology, Pisa University, Pisa, Italy.
Environ Health Perspect. 2009 Feb;117(2):203-8. doi: 10.1289/ehp.11769. Epub 2008 Sep 1.
The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes.
To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk.
A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency.
The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8).
Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.
健康个体外周血淋巴细胞中的染色体畸变（CA）频率与癌症风险相关。目前尚不清楚这种关联是否受个体易感性因素影响，如异生物代谢酶的基因多态性。
评估谷胱甘肽S-转移酶（GST）M1（GSTM1）和θ1（GSTT1）基因多态性作为CA与癌症风险关联的效应修饰因子的作用。
进行了一项病例对照研究，汇总了1974年至1995年在意大利、挪威和丹麦的三个实验室开展的细胞遗传学研究数据。从国家登记处检索到107例癌症病例，并与291名对照进行匹配。根据CA频率三分位数将受试者分为低、中、高组。通过建立贝叶斯模型分析数据，该模型包含了CA频率与癌症风险的先验信息。
CA频率与癌症风险之间的关联得到证实[OR（中）（比值比）（中）= 1.5，95%可信区间（CrI），0.9 - 2.5；OR（高）= 2.8，95% CrI，1.6 - 4.6]，而未观察到基因多态性的效应。在意大利亚组中观察到更强的关联（OR（高）= 9.4，95% CrI，2.6 - 28.0），该亚组细胞遗传学分析的技术变异性较低。CA水平与呼吸道癌症（OR（高）= 6.2，95% CrI，1.5 - 20.0）、泌尿生殖道癌症（OR（高）= 4.0，95% CrI，1.4 - 10.0）和消化道癌症（OR（高）= 2.8，95% CrI，1.2 - 5.8）尤其相关。
尽管研究组规模较小，但我们的结果证实了CA频率对癌症风险的预测性，排除了GSTM1和GSTT1基因多态性的强烈修饰作用。
