Djansugurova Leyla, Zhunussova Gulnur, Khussainova Elmira, Iksan Olzhas, Afonin Georgiy, Kaidarova Dilyara, Parker M Iqbal
Laboratory of Molecular Genetics, Institute of General Genetics and Cytology, Al-Farabi Ave., 93, Almaty, Kazakhstan, 050060,
Tumour Biol. 2015 Jan;36(1):279-89. doi: 10.1007/s13277-014-2641-2. Epub 2014 Sep 24.
This study presents the first results of a molecular-genetic study of colorectal cancer (CRC) in Kazakhstan. Blood samples were collected from patients diagnosed with rectal or colon cancer (249 individuals) as well as a control cohort of healthy volunteers (245 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Combined analysis of data obtained from individuals of either Kazakh or Russian decent showed a significant association with increased CRC risk in the following genotypes: DCC (32008376G/G and G/A versus A/A; OR = 3.45, 95 % confidence interval (95 %CI) = 1.75-6.81, χ (2) = 14.07, p < 0.0002), MLH1 (-93G/G versus G/A and A/A; OR = 1.45, 95 %CI = 1.02-2.07, χ (2) = 4.21, p < 0.04), TP53 (Pro72Pro; OR = 3.80, 95 %CI = 2.46-5.88, χ (2) = 61.27, p < 0.0001), combination GSTT1 deletions with heterozygotes versus normal homozygotes (OR = 1.43, 95 %CI = 1.00-2.04, χ (2) = 3.90, p < 0.05), and GSTM1 deletions (OR = 1.83, 95 %CI = 1.28-2.63, χ (2) = 11.04, p < .001). Analysis for ethnicity and smoking for each of the investigated polymorphisms showed that some genotypes can have a predictive value for susceptibility to CRC, at least those that demonstrate statistically significant ORs either for the combined mixed population of Kazakhstan or for both main ethnic groups separately (Kazakhs and Russians): TP53 Pro72Pro homozygous (for Kazakh-OR = 3.40, 95 %CI = 1.63-7.06, χ (2) = 11.35, p < 0.003; for Russian-OR = 4.69, 95 %CI = 2.53-8.66, χ (2) = 53.19, p < 0.0001) and GSTM1 deletions (for Kazakh-OR = 2.30, 95 %CI = 1.21-4.40, χ (2) = 8.42, p < 0.01; for Russian-OR = 1.64, 95 %CI = 1.01-2.66, χ (2) = 7.82, p < 0.02).
本研究展示了哈萨克斯坦结直肠癌（CRC）分子遗传学研究的首批成果。研究采集了经诊断患有直肠癌或结肠癌患者（249例个体）以及健康志愿者对照队列（245例个体）的血样，同时考虑了结直肠癌患者的年龄、性别、种族和吸烟习惯。对哈萨克族或俄罗斯族个体的数据进行综合分析后发现，以下基因型与结直肠癌风险增加显著相关：DCC（32008376G/G和G/A相较于A/A；比值比（OR）=3.45，95%置信区间（95%CI）=1.75 - 6.81，χ(2)=14.07，p<0.0002）、MLH1（-93G/G相较于G/A和A/A；OR=1.45，95%CI=1.02 - 2.07，χ(2)=4.21，p<0.04）、TP53（Pro72Pro；OR=3.80，95%CI=2.46 - 5.88，χ(2)=61.27，p<0.0001）、GSTT1缺失杂合子与正常纯合子组合（OR=1.43，95%CI=1.00 - 2.04，χ(2)=3.90，p<0.05）以及GSTM1缺失（OR=1.83，95%CI=1.28 - 2.63，χ(2)=11.04，p<0.001）。对每个研究的多态性进行种族和吸烟分析表明，某些基因型对结直肠癌易感性可能具有预测价值，至少对于哈萨克斯坦混合人群或两个主要种族群体（哈萨克族和俄罗斯族）分别具有统计学显著OR值的那些基因型：TP53 Pro72Pro纯合子（哈萨克族-OR=3.40，95%CI=1.63 - 7.06，χ(2)=11.35，p<0.003；俄罗斯族-OR=4.69，95%CI=2.53 - 8.66，χ(2)=53.19，p<0.0001）和GSTM1缺失（哈萨克族-OR=2.30，95%CI=1.21 - 4.40，χ(2)=8.42，p<0.01；俄罗斯族-OR=1.64，95%CI=1.01 - 2.66，χ(2)=7.82，p<0.02）。
