De Chaudhuri Sujata, Mahata Julie, Das Jayanta K, Mukherjee Angshuman, Ghosh Papiya, Sau Tanmoy Jyoti, Mondal Lakshmikanta, Basu Santanu, Giri Ashok K, Roychoudhury Susanta
Molecular and Human Genetics Division, Indian Institute of Chemical Biology, 4, Kolkata, India.
Mutat Res. 2006 Oct 10;601(1-2):102-12. doi: 10.1016/j.mrfmmm.2006.06.014. Epub 2006 Aug 22.
Although, more than six million people are endemically exposed to inorganic arsenic in West Bengal, India by drinking heavily contaminated groundwater, only about 300,000 people show arsenic induced skin lesions. This suggests that genetic variability plays an important role in arsenic induced skin lesions and skin cancers. Arsenic induced keratosis is considered as a possible precancerous state of in situ carcinoma. Several reports have suggested the role of p53 polymorphisms as potential marker for risk assessment of different types of cancers. This prompted us to study the association of three p53 polymorphisms with arsenic induced keratosis in a population exposed to arsenic through drinking water. A total of 366 unrelated individuals (177 individuals with arsenic induced keratosis and 189 individuals with no arsenic induced skin lesions) were recruited from North 24 Parganas, Nadia and Murshidabad districts between January 2003 and February 2005 for the study of the genotypic distribution of three p53 polymorphisms (16bp duplication at intron 3, codon 72 Arg/Pro and G>A at intron 6 [nt 13,494]) by PCR-RFLP. The arginine homozygous genotype at codon 72, and homozygous genotype of no duplication polymorphism at intron 3 were over represented in the individuals with keratosis compared with individuals with no skin lesions (OR=2.086; 95% CI=1.318-3.299 and OR=2.086; 95% CI=1.257-3.457, respectively). This study indicates that individuals carrying the arginine homozygous genotype at codon 72, and/or no duplication homozygous genotype at intron 3 are at risk for the development of arsenic induced keratosis.
在印度西孟加拉邦，超过600万人因饮用严重污染的地下水而长期接触无机砷，但只有约30万人出现砷诱发的皮肤病变。这表明基因变异性在砷诱发的皮肤病变和皮肤癌中起着重要作用。砷诱发的角化病被认为是原位癌可能的癌前状态。一些报告表明p53基因多态性可作为不同类型癌症风险评估的潜在标志物。这促使我们研究在通过饮用水接触砷的人群中，三种p53基因多态性与砷诱发的角化病之间的关联。2003年1月至2005年2月期间，从北24帕根那斯、纳迪亚和默西达巴德地区招募了366名无亲属关系的个体（177名有砷诱发角化病的个体和189名无砷诱发皮肤病变的个体），通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）研究三种p53基因多态性（内含子3的16bp重复、密码子72的精氨酸/脯氨酸以及内含子6的G>A [nt 13,494]）的基因型分布。与无皮肤病变的个体相比，有角化病的个体中密码子72的精氨酸纯合基因型以及内含子3无重复多态性的纯合基因型比例过高（OR = 2.086；95% CI = 1.318 - 3.299以及OR = 2.086；95% CI = 1.257 - 3.457）。这项研究表明，携带密码子72精氨酸纯合基因型和/或内含子3无重复纯合基因型的个体有发生砷诱发角化病的风险。
