不同代谢肥胖表型与女性乳腺癌发病风险关联:一项前瞻性队列研究

Association of Different Metabolic Obesity Phenotypes with Breast Cancer Risk in Women:a Prospective Cohort Study

背景早期研究发现超重/肥胖与女性乳腺癌发病风险增加有关。然而,有研究发现单纯分析超重/肥胖与女性乳腺癌的关联可能并不科学,因为超重/肥胖可分为不同代谢表型。目前关于不同代谢肥胖表型与乳腺癌关联的结论并不一致。目的通过队列研究分析不同代谢肥胖表型与女性乳腺癌发病风险的关联。方法本研究为前瞻性队列研究。选取2006年度和2008年度在开滦总医院及其附属共11家医院首次参与健康体检的女性开滦职工为研究对象(n=23406),对研究对象进行问卷调查、体格检查和实验室检查。根据代谢综合征和BMI的类型将研究对象分为代谢正常体质量正常(MHNW)组(n=12739)、代谢异常体质量正常(MUNW)组(n=1060)、代谢正常超重/肥胖(MHO)组(n=6394)和代谢异常超重/肥胖(MUO)组(n=3213)。对研究对象进行随访,以首次参加体检为随访起点,以新发乳腺癌、死亡或随访时间结束(2020-12-31)为随访终点。采用多因素Cox比例风险回归模型分析四组代谢表型与乳腺癌发病风险的关联。结果研究对象平均随访(13.26±1.85)年,乳腺癌新发病例为353例,总人群发病密度为11.38例/万人年。MHNW组、MUNW组、MHO组、MUO组发病例数分别为154、21、113、65例,发病密度依次为9.08、15.37、13.27、15.49例/万人年,乳腺癌累积发病率分别为1.22%、2.01%、1.67%、1.93%。多因素Cox比例风险回归模型分析结果显示,校正混杂因素后,与MHNW组相比,MHO组、MUO组乳腺癌发病风险分别增加42%(HR=1.42,95%CI=1.11~1.82)、59%(HR=1.59,95%CI=1.17~2.17)。按照绝经状态进行分层分析,结果显示:绝经前,与MHNW组相比,MUO组发病风险增加69%(HR=1.69,95%CI=1.01~2.83);绝经后,与MHNW组相比,MUNW组、MHO组和MUO组乳腺癌发病风险分别增加85%(HR=1.85,95%CI=1.09~3.14)、50%(HR=1.50,95%CI=1.06~2.13)、55%(HR=1.55,95%CI=1.05~2.28)。结论超重/肥胖是女性发生乳腺癌的危险因素,超重/肥胖合并代谢异常者乳腺癌发病风险进一步增加;绝经后,体质量正常但代谢异常者乳腺癌发病风险也增加。

Background Earlier studies have investigated the association between overweight/obesity and an elevated risk of breast cancer in women.However,some studies have found that it may not be scientifically accurate to solely analyze the association between overweight/obesity and breast cancer in women for overweight/obesity can be classified into different metabolic phenotypes.The current findings on the association of different metabolic phenotypes with breast cancer remain inconsistent.Objective To prospectively analyze the associations of different metabolic obesity phenotypes with the risk of breast cancer in women.Methods In this prospective cohort study,female employees(n=23406)of Kailuan Group who participated in physical examinations for the first time in Kailuan General Hospital and its 11 affiliated hospitals from 2006 to 2008 were selected as the study subjects and received questionnaire investigation,physical examination and laboratory tests.The study subjects were divided into the four groups based on the types of metabolic syndrome and BMI,including metabolically healthy normal weight(MHNW)group(n=12739),metabolically unhealthy normal weight(MUNW)group(n=1060),metabolically healthy overweight/obese(MHO)group(n=6394),and metabolically unhealthy overweight/obese(MUO)group(n=3213).The subjects were followed up,with the first physical examination attended as the starting point,and new onset breast cancer,death,or the end of follow-up time(2020-12-31)as the endpoints.Multivariate Cox proportional hazard regression model was used to estimate the association of the four groups with the risk of breast cancer.Results During an average follow-up of(13.26±1.85)years,with 353 new cases of breast cancer and an incidence density of 11.38 cases per 10000 person-years in the total population.The incidence cases in the MHNW,MUNW,MHO,and MUO groups were 154,21,113,and 65,respectively,with the incidence density of 9.08,15.37,13.27,and 15.49 per 10000 person-years,and the cumulative incidence of 1.22%,2.01%,1.67%,and 1.93%,respectively.Multivariate Cox proportional hazard regression model analysis,after adjusting for confounders,showed that compared with the MHNW group,the risk of breast cancer was increased by 42%(HR=1.42,95%CI=1.11-1.82)and 59%(HR=1.59,95%CI=1.17-2.17)in the MHO group and MUO group,respectively.Stratified analysis by menopausal status showed that compared to the MHNW group,the MUO group was associated with a 69%increase in risk of premenopausal breast cancer(HR=1.69,95%CI=1.01-2.83).The risk of postmenopausal breast cancer was increased by 85%(HR=1.85,95%CI=1.09-3.14),50%(HR=1.50,95%CI=1.06-2.13),and 55%(HR=1.55,95%CI=1.05-2.28)for the MUNW,MHO,and MUO groups,respectively,compared to the MHNW group.Conclusion Overweight/obesity is a risk factor for female breast cancer,and overweight/obesity with metabolic abnormalities further increases the risk of breast cancer.Additionally,normal weight postmenopausal women who are metabolically unhealthy may be at an increased risk of postmenopausal breast cancer.