CAJ | 학술논문

目的：探讨毛细血管扩张性共济失调症突变（ATM）基因的多态性和人乳头瘤病毒16（HPV16）感染对于食管鳞状细胞癌发病风险的协同作用。方法对303例食管鳞状细胞癌患者和304例无癌对照者的外周血标本进行ATM基因分型和HPV16的血清学检测。ATM的单核苷酸多态性（SNP）位点（rs373759，rs189037）通过荧光定量Taq‐Man技术进行基因分型，HPV16的血清学状态通过酶联免疫吸附实验（ELISA）检测。危险因素与食管鳞状细胞癌发病风险的相关性采用非条件Logistic回归模型进行统计分析。结果在饮酒人群中，rs373759的基因型与食管鳞状细胞癌的发病风险存在明显的相关性（Ptrend＝0.006），相比于CC型，CT型的发病风险提高了1.82倍（95％CI1.10，3.01），TT型的发病风险提高了2.50倍（95％CI1.15，5.45）；相比于rs189037的GG基因型，rs189037AG/AA型人群中食管鳞状细胞癌的发病风险有轻度提高（OR值1.64；95％CI1.00，2.68）。HPV16血清学阳性是饮酒人群（OR值1.92；95％CI1.20，3.07）和吸烟人群（OR值1.96；95％CI1.26，3.50）中食管鳞状细胞癌的易感因素。rs373759的基因型和HPV16血清学状态对于食管鳞状细胞癌的发病风险有交互作用（PG×E＝0.009，OR值2.04；95％CI1.19，3.48）。相比于HPV16阴性且rs373759CC型的人群，HPV阴性且rs373759CT/TT型的人群发病风险增高（OR值2.43；95％CI1.25，4.72），HPV阳性且rs373759CC型的人群发病风险进一步增高（OR值2.51；95％CI1.23，5.13），HPV16阳性且rs373759CT/TT型的人群食管鳞状细胞癌发病风险增加了3.83倍（95％CI1.93，7.61）。结论HPV16血清学阳性协同ATMrs373759的突变基因型增加了饮酒人群中食管鳞状细胞癌的发病风险。
목적：탐토모세혈관확장성공제실조증돌변（ATM）기인적다태성화인유두류병독16（HPV16）감염대우식관린상세포암발병풍험적협동작용。방법대303례식관린상세포암환자화304례무암대조자적외주혈표본진행ATM기인분형화HPV16적혈청학검측。ATM적단핵감산다태성（SNP）위점（rs373759，rs189037）통과형광정량Taq‐Man기술진행기인분형，HPV16적혈청학상태통과매련면역흡부실험（ELISA）검측。위험인소여식관린상세포암발병풍험적상관성채용비조건Logistic회귀모형진행통계분석。결과재음주인군중，rs373759적기인형여식관린상세포암적발병풍험존재명현적상관성（Ptrend＝0.006），상비우CC형，CT형적발병풍험제고료1.82배（95％CI1.10，3.01），TT형적발병풍험제고료2.50배（95％CI1.15，5.45）；상비우rs189037적GG기인형，rs189037AG/AA형인군중식관린상세포암적발병풍험유경도제고（OR치1.64；95％CI1.00，2.68）。HPV16혈청학양성시음주인군（OR치1.92；95％CI1.20，3.07）화흡연인군（OR치1.96；95％CI1.26，3.50）중식관린상세포암적역감인소。rs373759적기인형화HPV16혈청학상태대우식관린상세포암적발병풍험유교호작용（PG×E＝0.009，OR치2.04；95％CI1.19，3.48）。상비우HPV16음성차rs373759CC형적인군，HPV음성차rs373759CT/TT형적인군발병풍험증고（OR치2.43；95％CI1.25，4.72），HPV양성차rs373759CC형적인군발병풍험진일보증고（OR치2.51；95％CI1.23，5.13），HPV16양성차rs373759CT/TT형적인군식관린상세포암발병풍험증가료3.83배（95％CI1.93，7.61）。결론HPV16혈청학양성협동ATMrs373759적돌변기인형증가료음주인군중식관린상세포암적발병풍험。
Objective To investigate the synergistic effects of human papilloma virus 16(HPV16)and the Ataxia telangiec‐tasia mutated(ATM)gene polymorphism on the risk of esophageal squamous cell carcinoma(ESCC).Methods The peripheral blood of 303 ESCC patients and 304 cancer‐free controls was evaluated for the ATM polymorphism and HPV 16 serology.ATM single nucleotide polymorphism (SNP)loci(rs373759 ,rs189037)were genotyped by TaqMan fluorescent quantitative tech‐niques.The serum status of HPV16 was measured by enzyme‐linked immunosorbent assay(ELISA).The associations of risk factors with the ESCC risk were staistically analysized non‐conditional Logistic regression models.Results In the drinking pop‐ulation ,rs373759 genotypes were significantly associated with the risk of ESCC (Ptrend=0.006). People with rs373759 CT geno‐type had a 1.82‐fold(95% CI 1.10 ,3.01)increased risk for ESCC and those with rs373759 TT genotype had a 2.50‐fold(95%CI 1.15 ,5.45)increased risk for ESCC when compared with rs373759 CC genotype.Compared with rs189037 GG genotype ,the participants with rs189037 AG/AA genotypes were associated with a mildly increased risk of ESCC (OR 1.64 ;95% CI 1.00 , 2.68).HPV16 seropositivity was a susceptible factor for ESCC in drinkers (OR 1.92 ;95% CI 1.20 ,3.07)and smokers(OR 1.96 ;95% CI 1.26 ,3.50).rs373759 genotypes and HPV16 serological status had interactions on the risk of ESCC (PG×E =0.009 ,OR 2.04;95% CI 1.19 ,3.48). The risk of ESCC was elevated in the group with negative HPV 16 and rs373759 CT/TT genotypes(OR 2.43 ;95% CI 1.25 ,4.72) ,the group with positive HPV16 and rs373759 CC genotype(OR 2.51 ;95% CI 1.23 , 5.13) ,and the group with positive HPV16 and rs373759 CT/TT genotypes (OR 3.83;95% CI 1.93 ,7.61)relative to the group of negative HPV16 and rs373759 CC genotype.Conclusion HPV16 synergized with ATM rs373759 variants increases the risk of ESCC in drinkers.