泰国常见癌症中维生素D结合蛋白的Gc基因单核苷酸多态性
Single nucleotide polymorphisms in the Gc gene for vitamin D binding protein in common cancers in Thailand.
作者信息
Maneechay Wanwisa, Boonpipattanapong Teeranut, Kanngurn Samornmas, Puttawibul Puttisak, Geater Sarayut Lucien, Sangkhathat Surasak
机构信息
Central Research Laboratory, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand E-mail :
出版信息
Asian Pac J Cancer Prev. 2015;16(8):3339-44. doi: 10.7314/apjcp.2015.16.8.3339.
BACKGROUND
This case-control study aimed to determine if there were any associations between the two single nucleotide polymorphisms (SNPs) in Gc, rs7041 (Asp416Glu) and rs4588 (Thr420Lys) and 3 common cancers (breast, lung and colorectal) in Thai patients.
MATERIALS AND METHODS
Two hundred and eighty two colorectal, 101 breast and 113 lung cancer patients were recruited from one institute during 2011-2013. The controls were age-matched volunteers who had a negative history of index cancers. In addition, vitamin D levels were compared among different genotypes in the 2 SNPs.
RESULTS
The minor allele frequencies of rs7041 (G) and rs4588 (A) were 0.32 and 0.24, respectively. Under the dominant model, the study found significant associations between minor-allele genotypes of the SNP rs7041 (TG/GG) and lung cancer (odds ratio [OR] 1.78, 95% CI 1.05-3.03). When subgroup analysis was performed according to sex and age at diagnosis, the study found that the minor- allele genotypes of rs7041 (TG/GG) were significantly associated with colorectal cancer in patients whose age at diagnosis was more than 60 years (OR 1.67, 95%CI 1.06-2.61) and the minor-allele genotypes of rs4588 (CA/AA) were significantly associated with colorectal cancer in males aged 60 years or less (OR 2.34, 95%CI 1.25-4.37). When SNP combinations (rs7041-rs4588) were examined, the TT-CA combination had a significant protective association with lung cancer (OR 0.44, 95% CI 0.22-0.85). On evaluation of serum 25(OH)D levels in 205 individuals without cancer (males 144, females 61), the proportion of subjects with low serum vitamin D (< 20 ng/ml) in those harboring CA or AA genotypes of rs4588 (41.7%) was significantly higher than the CC genotype (15.5%, p-value < 0.01).
CONCLUSIONS
Genetic polymorphisms in Gc were associated with lung and colorectal cancers in Thai patients. Lower serum 25(OH)D in minor variants of rs4588 may explain this association.
背景
本病例对照研究旨在确定泰国患者中维生素转运蛋白（Gc）基因的两个单核苷酸多态性（SNP），即rs7041（Asp416Glu）和rs4588（Thr420Lys）与三种常见癌症（乳腺癌、肺癌和结直肠癌）之间是否存在关联。
材料与方法
2011年至2013年期间，从一家机构招募了282例结直肠癌患者、101例乳腺癌患者和113例肺癌患者。对照组为年龄匹配且无相关癌症病史的志愿者。此外，还比较了这两个SNP不同基因型之间的维生素D水平。
结果
rs7041（G）和rs4588（A）的次要等位基因频率分别为0.32和0.24。在显性模型下，研究发现SNP rs7041的次要等位基因基因型（TG/GG）与肺癌之间存在显著关联（优势比[OR]1.78，95%置信区间1.05 - 3.03）。当根据诊断时的性别和年龄进行亚组分析时，研究发现rs7041的次要等位基因基因型（TG/GG）与诊断年龄大于60岁的患者的结直肠癌显著相关（OR 1.67，95%置信区间1.06 - 2.61），而rs4588的次要等位基因基因型（CA/AA）与60岁及以下男性的结直肠癌显著相关（OR 2.34，95%置信区间1.25 - 4.37）。当检查SNP组合（rs7041 - rs4588）时，TT - CA组合与肺癌存在显著的保护关联（OR 0.44，95%置信区间0.22 - 0.85）。在对205名无癌症个体（男性144名，女性61名）的血清25(OH)D水平进行评估时，携带rs4588的CA或AA基因型的受试者中血清维生素D水平低（< 20 ng/ml）的比例（41.7%）显著高于CC基因型（15.5%，p值< 0.01）。
结论
Gc基因的遗传多态性与泰国患者的肺癌和结直肠癌有关。rs4588次要变体中较低的血清25(OH)D水平可能解释了这种关联。
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