| Summary: | 博士 === 中山醫學大學 === 醫學研究所 === 102 === Urothelium covers the epithelial lining of the urinary tract from the renal calyces to the bladder. The most frequent malignant tumor of urinary tract is urothelial cell carcinoma (UCC). In Taiwan, bladder cancer is the ninth leading malignancy among men and the sixteenth leading malignancy among women. Renal pelvis and ureter cancer is the fifteen leading cancer among men and the thirteen leading cancer among women. UCC composed more than 90% of the cancer in both genders. Carbonic anhydrase (CA), a family of zinc metalloenzymes, can efficiently catalyze the reversible processes of hydration-dehydration of CO2 and HCO3-. CAIX helps to keep a normal pH in tumor cells in a hypoxic microenvironment and allow tumor cell proliferation. CAIX, which is not expressed in most benign tissues, is reportedly over-expressed in several types of carcinomas and generally considered a marker of malignancy. Single nucleotide polymorphism (SNP) is a variation in the DNA sequence that occurs when a nucleotide (A, T, C, or G) is changed in at least 1% of a certain population. Previous study showed that SNP of CA9 is associated with overall survival for metastatic renal cell carcinoma and might alter oral cancer susceptibility and metastasis. The current study explored the effect of CA9 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma and the clinicopathological status.
A total of 442 participants, including 221 healthy people and 221 patients with UCC, were recruited for this study. Medical information for the cases was obtained from their medical records, and included cigarette smoking history, TNM clinical staging and histological grade. Their genomic DNA samples were subjected to polymerase chain reaction (PCR) and real-time PCR genotyping analysis to analyze the genetic polymorphisms. Allelic discrimination of the CA9 +201(rs2071676), +1081(rs3829078),+1584(rs1048638) and 376del393 allelic polymorphisms were assessed.
After adjusting for other co-variants, the individuals carrying at least one A allele at CA9 rs1048638 had a 2.303-fold risk of developing UCC than did wild-type (CC) carriers. Furthermore, UCC patients who carried at least one A allele at rs1048638 had a higher invasive stage risk (p< 0.05) than did patients carrying the wild-type allele. Moreover, among the UCC patients with smoking, people with at least one A allele of CA9 polymorphisms (rs1048638) had a 4.75-fold (95% Confidence Interval = 1.204–18.746) increased risk of invasive cancer. The rs1048638 polymorphic genotypes of CA9 might contribute to the prediction of susceptibility to and pathological development of UCC. This study provided insight into risk factors associated with CA9 variants in carcinogenesis of UCC in Taiwan.
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