来自XPD、hOGG1和ITGA2基因多态性的单倍型CGC增加了马来西亚鼻咽癌的发病风险。
Haplotype CGC from XPD, hOGG1 and ITGA2 polymorphisms increases the risk of nasopharyngeal carcinoma in Malaysia.
作者信息
Ban Eng-Zhuan, Lye Munn-Sann, Chong Pei Pei, Yap Yoke-Yeow, Lim Siew Ying Crystale, Abdul Rahman Hejar
机构信息
Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
出版信息
PLoS One. 2017 Nov 9;12(11):e0187200. doi: 10.1371/journal.pone.0187200. eCollection 2017.
BACKGROUND
8-oxoG, a common DNA lesion resulting from reactive oxygen species (ROS), has been shown to be associated with cancer initiation. hOGG1 DNA glycosylase is the primary enzyme responsible for excision of 8-oxoG through base excision repair (BER). Integrins are members of a family of cell surface receptors that mediate the cell-cell and extracellular matrix (ECM) interactions. Integrins are involved in almost every aspect of carcinogenesis, from cell differentiation, cell proliferation, metastasis to angiogenesis. Loss of ITGA2 expression was associated with enhanced tumor intravasation and metastasis of breast and colon cancer. XPD gene encodes DNA helicase enzyme that is involved in nucleotide excision repair (NER). It is shown in previous research that XPD homozygous wildtype Lys/Lys genotype was associated with higher odds of NPC.
METHODS
We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.
RESULTS
No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58).
CONCLUSION
The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.
背景
8-氧代鸟嘌呤（8-oxoG）是由活性氧（ROS）导致的常见DNA损伤，已被证明与癌症发生有关。hOGG1 DNA糖基化酶是通过碱基切除修复（BER）切除8-氧代鸟嘌呤的主要酶。整合素是一类细胞表面受体家族的成员，介导细胞间和细胞外基质（ECM）相互作用。整合素几乎参与了癌症发生的各个方面，从细胞分化、细胞增殖、转移到血管生成。ITGA2表达缺失与乳腺癌和结肠癌的肿瘤内渗和转移增强有关。XPD基因编码参与核苷酸切除修复（NER）的DNA解旋酶。先前的研究表明，XPD纯合野生型Lys/Lys基因型与鼻咽癌的较高发病几率相关。
方法
我们进行了一项1对N的病例对照研究，纳入300例鼻咽癌（NPC）病例和533例按年龄、性别和种族匹配的对照，以研究hOGG1 Ser326Cys、ITGA2 C807T和XPD Lys751Gln多态性对NPC风险的影响。进行连锁不平衡和单倍型分析以探索等位基因组合与NPC风险的关联。采用限制性片段长度多态性（RFLP-PCR）进行DNA基因分型。
结果
在调整年龄、性别、种族、吸烟、饮酒和咸鱼消费后，未观察到hOGG1 Ser326Cys和ITGA2 C807T多态性与NPC风险之间存在显著关联。XPD Lys751Gln多态性的Lys/Lys基因型与NPC风险增加相关（OR = 1.60，95%CI = 1.06 - 2.43）。有吸烟史的受试者（OR = 1.81，95%CI = 1.26 - 2.60）和10岁前食用咸鱼的受试者（OR = 1.77，95%CI = 1.30 - 2.42）患NPC的几率增加。与参考AGC单倍型相比，CGC单倍型发生NPC的几率显著更高（OR = 2.20，95%CI = 1.06 - 4.58）。
结论
hOGG1、ITGA2和XPD多态性的CGC等位基因组合与NPC几率增加显著相关。
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