Visuvanathan Shaneeta, Chong Pei-Pei, Yap Yoke-Yeow, Lim Chin-Chye, Tan Meng-Kuan, Lye Munn-Sann
Department of Community Health Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia E-mail :
Asian Pac J Cancer Prev. 2014;15(6):2747-51. doi: 10.7314/apjcp.2014.15.6.2747.
DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population.
We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequencies, haplotype and linkage disequilibrium were determined using SNPstat software.
For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotype association with NPC gave a p-value of 0.054.
Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.
DNA修复通路在维持人类基因组方面发挥着关键作用。先前的研究将DNA修复基因多态性（XPD Lys751Gln、XRCC1 Arg280His和XRCC1 Arg399Gln）与鼻咽癌联系起来。这些非同义多态性可能会改变DNA修复能力，从而增加或降低易感性。本研究旨在确定马来西亚人群中鼻咽癌病例和对照者XPD密码子751、XRCC1密码子280和密码子399多态性的基因型分布以及单倍型关联。
我们从马来西亚吉隆坡的两家医院选取了157例鼻咽癌病例和136例对照者进行本研究。通过PCR-RFLP分析对所研究的多态性进行基因分型，并使用SNPstat软件确定等位基因和基因型频率、单倍型及连锁不平衡情况。
对于XPD Lys751Gln多态性，病例组中Lys等位基因的频率高于对照组（94.5%对85.0%）。对于XRCC1 Arg280His多态性，病例组和对照组中Arg等位基因的频率分别为90.0%和89.0%，对于XRCC1 Arg399Gln，病例组和对照组中Arg等位基因的频率分别为72.0%和72.8%。所有这三种多态性均处于连锁不平衡状态。这三种多态性及其与鼻咽癌关联的单倍型分析中，单倍型CGC与AGC等位基因组合的优势比为1.93（95%CI：0.90 - 4.16）。与鼻咽癌的总体单倍型关联的p值为0.054。
我们的研究提供了马来西亚人群中XRCC1Arg280His、XRCC1 Arg399Gln和XPD Lys751Gln多态性等位基因和基因型频率的估计值，且显示其与鼻咽癌无关联。
