CAJ | 학술논문

目的探讨谷氨酰半胱氨酸合成酶催化亚基(GCLC)rs17883901多态性位点对BMI与乳腺癌关联的影响.方法于2008年10月至2010年6月对中山大学3所附属医院新诊断的839例乳腺癌患者(病例组)在接受治疗前及同时期863名年龄频数匹配的对照(对照组)进行问卷调查和收集血样；采用基质辅助激光解吸-飞行时间质谱仪(MALDI-TOF-MS),在Sequenom平台检测rs17883901位点基因型；采用非条件logistic回归分析计算BMI和GCLC与乳腺癌关联的OR值及其95％CI.结果 (1)病例组和对照组接受调查时当前的BMI、20岁时的BMI和GCLCrs17883901位点分布的差异均无统计学意义(P=0.44、0.52和0.47)；(2)未发现当前的BMI与绝经前及绝经后乳腺癌风险相关,20岁时BMI为18.5～22.9 kg/m2可降低绝经前乳腺癌风险(OR=0.69,95％CI:0.48～1.00),而未发现其与绝经后乳腺癌风险相关；(3)在GCLC rs17883901位点突变型CT/TT人群中,当前的BMI≥25 kg/m2显著增加乳腺癌风险(OR=1.91,95％CI:1.09～ 3.36),而20岁时BMI为18.5 ～ 22.9 kg/m2与降低乳腺癌风险有关(OR=0.56,95％CI:0.31 ～ 0.99).当前的BMI与GCLC基因多态性对乳腺癌发生风险存在交互作用(P=0.043),而20岁时的BMI与GCLC交互项无统计学意义(P=0.15).结论 20岁时增加BMI可能是绝经前乳腺癌的保护因素；GCLCrs17883901位点本身与乳腺癌发生风险无显著关联,但其变异基因型可使当前的肥胖状态(BMI≥25 kg/m2)显著增加乳腺癌发生风险.
목적 탐토곡안선반광안산합성매최화아기(GCLC)rs17883901다태성위점대BMI여유선암관련적영향.방법 우2008년10월지2010년6월대중산대학3소부속의원신진단적839례유선암환자(병례조)재접수치료전급동시기863명년령빈수필배적대조(대조조)진행문권조사화수집혈양；채용기질보조격광해흡-비행시간질보의(MALDI-TOF-MS),재Sequenom평태검측rs17883901위점기인형；채용비조건logistic회귀분석계산BMI화GCLC여유선암관련적OR치급기95％CI.결과 (1)병례조화대조조접수조사시당전적BMI、20세시적BMI화GCLCrs17883901위점분포적차이균무통계학의의(P=0.44、0.52화0.47)；(2)미발현당전적BMI여절경전급절경후유선암풍험상관,20세시BMI위18.5～22.9 kg/m2가강저절경전유선암풍험(OR=0.69,95％CI:0.48～1.00),이미발현기여절경후유선암풍험상관；(3)재GCLC rs17883901위점돌변형CT/TT인군중,당전적BMI≥25 kg/m2현저증가유선암풍험(OR=1.91,95％CI:1.09～ 3.36),이20세시BMI위18.5 ～ 22.9 kg/m2여강저유선암풍험유관(OR=0.56,95％CI:0.31 ～ 0.99).당전적BMI여GCLC기인다태성대유선암발생풍험존재교호작용(P=0.043),이20세시적BMI여GCLC교호항무통계학의의(P=0.15).결론 20세시증가BMI가능시절경전유선암적보호인소；GCLCrs17883901위점본신여유선암발생풍험무현저관련,단기변이기인형가사당전적비반상태(BMI≥25 kg/m2)현저증가유선암발생풍험.
Objective To investigate the interaction of body mass index (BMI) and a single nucleotide polymorphism (SNP,rs17883901) in catalytic subunit of glutamate-cysteine ligase (GCLC) on breast cancer risk.Methods A total of 839 women with incident breast cancer and 863 age-matched controls without cancer were recruited at the same period in three affiliated hospitals of Sun Yat-sen University in Guangzhou from October 2008 to June 2010.GCLC rs17883901 was genotyped by MALDI-TOF-MS.Binary unconditional logistic regression was applied to calculate odds ratios and 95％ confidence intervals.Results The difference of present BMI and BMI at age 20 was not statistically significant between cases and controls,either as the genotypes of GCLC.No association was found between BMI at present and premenopausal or postmenopausal breast cancer risk.But we found that women who had a BMI at age 20 of 18.5 to 22.9 had a marginally decreased risk of premenopausal breast cancer [OR and 95％CI:0.69 (0.48,1.00)].Among women with CT/TT genotypes,whose present BMI was greater than 25 had a increased risk [OR and 95％CI:1.91 (1.09,3.36)] of breast cancer and a decreased risk [OR and 95％CI:0.56(0.31,0.99)] with a BMI at age 20 of 18.5 to 22.9.There was a interaction between GCLC gene (rs17883901)and BMI at present in breast cancer risk (P=0.043),which was not found between rs17883901 and BMI at age 20.Conclusion Our findings indicate BMI at age 20 may be a protective factor of premenopausal breast cancer,while no association appears between GCLC (rs17883901) and breast cancer.Obesity at present may significantly increase the risk of breast cancer among women with CT/TT genotypes of GCLC (rs17883901).