Significant association of caveolin-1 (CAV1) genotypes with upper urothelial tract cancer.
OBJECTIVE
Upper urothelial tract cancer is unusually of high incidence in Taiwan and it is valuable to study the specificity of this disease in Taiwan and compare the corresponding findings with those of Western countries. In the literature, it has been reported that single nucleotide variation of caveolin-1 gene (CAV1) plays an important role in risk of several types of cancer, such as hepatoma, leukemia, nasopharyngeal carcinoma, oral, breast, bladder and prostate cancer, but we are not aware of any reports on upper urothelial tract cancer. The aim of this study was to evaluate the association of six polymorphic genotypes of CAV1 with upper urothelial tract cancer within a Taiwanese population.


METHODS
A total of 218 patients with upper urothelial tract cancer and 580 healthy controls in central Taiwan were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) for six CAV1 polymorphic genotypes, C521A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T28608A (rs3757733), T29107A (rs7804372), and G32124A (rs3807992), and their association with upper urothelial tract cancer susceptibility was examined.


RESULTS
The distribution of genotypes of CAV1 rs3807987 and rs7804372 were significantly different between cancer patient and control groups (p=0.0188 and 0.0090, respectively), while those for CAV1 rs1997623, rs12672038, rs3757733 and rs3807992 were not significant (p>0.05). The haplotype analysis of the two polymorphic genotypes showed that compared with the GG/AT, and GG/AA haplotypes of CAV1 rs3807987/rs7804372, those carrying GG/TT, AG/TT and AA/TT variants have a significantly increased risk of upper urothelial tract cancer (odds ratio=1.61, 1.50 and 2.67, 95% confidence interval=1.05-2.47, 1.18-1.90, and 1.37-5.18, respectively). On the contrary, other haplotype variants conferred non-significant elevated risk.


CONCLUSIONS
Our results suggest that individual and combined CAV1 rs3807987/rs7804372 genotypes are involved in predisposition to upper urothelial tract cancer in the Taiwanese population.
Terry Fox Cancer Research Laboratory, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404 Taiwan, R.O.C. datian@mail.cmuh.org.tw; artbau2@gmail.com.
Wen-Shin
WS
Chang
Song-Shei
SS
Lin
Fang-Jing
FJ
Li
Chia-Wen
CW
Tsai
Long-Yuan
LY
Li
Chi-Shun
CS
Lien
Wen-Ling
WL
Liao
Hsi-Chin
HC
Wu
Chang-Hai
CH
Tsai
Tzu-Ching
TC
Shih
Da-Tian
DT
Bau
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D013624:Taiwan / Q000453:epidemiology; D014571:Urologic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1
CAV1; genotype; polymorphism; upper urothelial track cancer