Osawa Kayo, Nakarai Chiaki, Akiyama Minami, Hashimoto Ryuta, Tsutou Akimitsu, Takahashi Juro, Takaoka Yuko, Kawamura Shiro, Shimada Etsuji, Tanaka Kenichi, Kozuka Masaya, Yamamoto Masahiro, Kido Yoshiaki
Faculty of Health Sciences, Kobe University Graduate School of Health Sciences, and Clinical Laboratory, Otemae Hospital, Osaka, Japan.
Asian Pac J Cancer Prev. 2012;13(5):2311-4. doi: 10.7314/apjcp.2012.13.5.2311.
Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association of UGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65; 95% confidence interval [95%CI], 0.9-3.1, P=0.107; adjusted OR 1.95, 95%CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statistically significant (crude OR: 26.40, 95%CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95%CI: 2.8-164.1, P=0.003). The joint effect of tobacco exposure and UGT1A6 polymorphisms was significantly associated with colorectal cancer risk in non-smokers (crude OR, 2.11; 95%CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95%CI 1.0-6.7, P=0.042). In conclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC risk in the Japanese population. In particular, UGT1A6 polymorphisms may strongly increase CRC risk through the formation of carcinogens not associated with smoking.
尿苷二磷酸葡萄糖醛酸基转移酶1A6（UGT1A6）和1A7（UGT1A7）的基因多态性可能导致基因不稳定和结直肠癌的发生。我们的目的是测量这些修复基因的多态性与吸烟在结直肠癌（CRC）中的相互作用。根据吸烟包年数，将68例CRC患者和112例非癌症对照者分为非吸烟者和吸烟者组。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测UGT1A6和UGT1A7的基因多态性。我们发现UGT1A6多态性与CRC风险之间存在弱关联（粗比值比[OR]，1.65；95%置信区间[95%CI]，0.9 - 3.1，P = 0.107；调整后OR 1.95，95%CI 1.0 - 3.8，P = 0.051）。UGT1A7多态性的OR值具有统计学意义（粗OR：26.40，95%CI：3.5 - 198.4，P = 0.001；调整后OR：21.52，95%CI：2.8 - 164.1，P = 0.003）。烟草暴露与UGT1A6多态性的联合作用与非吸烟者的结直肠癌风险显著相关（粗OR，2.11；95%CI，0.9 - 5.0，P = 0.092；调整后OR 2.63，95%CI 1.0 - 6.7，P = 0.042）。总之，我们的研究结果表明，UGT1A6和UGT1A7基因多态性与日本人群的CRC风险相关。特别是，UGT1A6多态性可能通过形成与吸烟无关的致癌物而强烈增加CRC风险。
