Functional Polymorphisms Of JWA Gene -76G＞C And 454C＞A Are Associated With Risk Of Bladder Cancer

Cervical cancer is the second most common cancer among women worldwide. There were 500 thousands new cervical cancer cases every year and half of this happened in Asian country. In our country there are about 13 thousands new cervical cancer cases and about 2 thousands to 3 thousands cases who died of this cancer every year. In the recent years the incidence and mortality of cervical cancer is continually increasing in China and the new cases are younger than before. JWA gene was initially isolated from ATRA-treated primary human tracheal bronchial epithelial cells by Zhou et al, which was mapped on chromosome 3p14, consisting of 3 exons and 2 introns. The full length of cDNA sequence of the gene contains 2114 nucleotides, which encoding 188 amino acids. Within the identified 3000 base pairs of promoter sequence of the gene, several cis-response elements, such as phorbol ester response element(TRE),stress response element(SRE)and the retinoic acid response element(rare)were identified. Previous investigation have demonstrated that JWA gene was not only important for chemicals(e.g. ATRA)mediated directional cell differentiation and apoptosis in primary cultured APL cells and leukemia cell lines, but also was actively responsive to environmental stress stimulations(e.g. heat shock, oxidative stress).JWA positively involved in the DNA damage and repair process induced by H₂O₂ and B[a]P induced oxidative stress, suggesting that JWA may be involved in signaling of DNA damage and repair process.More and more evidence support that SNP in genes involved in biological process have association with cancer. As useful genetic biomarkers, some SNPs were identified to be associated with altered susceptibility to diseases, including cancer. Most SNPs are usually located near a gene found to be associated with a certain disease, occasionally, a SNP may be associated with development of a disease and, therefore, it can be used to search for and isolated the disease-causing gene.Latest investigation has demonstrated that two novel polymorphisms in the JWA gene (-76G>Cå’Œ723T>G) were associated with risk of bladder cancer, leukemia and digestive system cancers. The -76G>C could increase the risks of the above-mentioned cancers.The -76C allele might decrease or prevent the role of the JWA promoter in regulating the transcription of the JWA gene, resulting in down regulation or deletion of the JWA gene expression, particularly in the presence of oxidative stress. Therefore JWA gene may play a role in DNA damage-associateddevelopment of cancers and that its variants may contribute to individualvariation in susceptibility to environmentally induced cancer.[Objective] To investigate the association between of JWA gene singlenucleotide polymorphisms and the risk of cervical cancer.[Methods] In a hospital-based case-control study of 227 cervical patients and333 cancer-free controls frequency-matched by age, the genotype of the -76G>C,454C>A and 723T>G polymorphisms of JWA gene were detected by thepolymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method; the interaction of menarche age, reproductive age for thefirst time (RAFT) and parity were further analyzed.[Results] A significant increased risk of cervical cancer was found to beassociated with the -76GC genotype compared with the -76GG genotype(OR=1.84, 95%CI=1.21～2.78), and 454AA genotype compared with the454CC genotype (OR=1.84, 95%CI=1.08～3.14). Moreover, individuals with3～5 risk alleles will further increase the risk of cervical cancer accompaniedwith early menarche age, late RAFT and many parity. There was no associationwas found between JWA 723T>G polymorphism and cervical cancer.[Conclusion] The JWA-76G>C and 454C>A polymorphisms might positivelycontribute to the etiology of cervical cancer.