上海女性月经生育模式的变化及对乳腺癌发生趋势的影响

　上海交通大学肿瘤研究所流行病学研究室 徐望红

　　[摘要]目的：利用上海女性健康队列(SWHS)收集的数据，比较不同出生队列女性的月经生育史及乳腺癌发生情况，并分析两者的关联，以评估上海女性月经生育模式变化对乳腺癌发生趋势的影响。方法：SWHS是一项共有73,321名40-70岁(1926年-1960年出生)上海市区健康女性参加的大规模前瞻性队列研究。所有对象在1996年9月至2000年5月期间完成基线调查，内容包括个人信息、详细的月经生育史和生活方式等信息。乳腺癌新发病例的收集通过每2年一次的主动随访和每年一次与上海肿瘤登记数据的记录联动进行，并通过病史摘录和病理切片复核确认。Cox回归模型用于估计整个队列及不同出生队列中与月经生育因素相关的乳腺癌的风险比及95%可信限。结果：截止至2006年12月31日，通过对队列人群平均8.00年(581,838人年)的随访，共收集并确认乳腺癌新发病例664例。所有对象按出生年份分组，发现，与年老的出生队列相比，年轻队列初潮早，自然绝经晚，结婚和初产年龄大，初潮和初产间隔时间长，怀孕及活产次数少，哺乳时间短，并有较高的年龄别乳腺癌发病率。调整年龄后，这些因素以及激素替代治疗均与乳腺癌呈正向关联。进一步的相互调整可减弱这些正向关联。在整个队列中，只有活产次数、初产年龄、初潮和初产间隔时间以及激素替代治疗是乳腺癌的独立危险因素。按出生队列进行分层分析，观察到不同的月经生育史与乳腺癌的关联模式。在1926-40年出生队列中，活产及活产次数多与乳腺癌呈显著的负向关联，而在1941-50年出生队列中观察到显著的初产年龄以及初潮和初产间隔时间与乳腺癌发生的剂量反应关系，是否哺乳只在1951-60年出生队列中与乳腺癌有显著的关联。乳腺癌的发生在年轻队列中更多地归因于月经生育因素。结论：研究结果提示，不同出生队列女性月经生育模式的变化可能部分解释该人群中乳腺癌发病率的上升。

　　The role of menstrual and reproductive factors in the incidence of breast cancer in Chinese women, a report from the Shanghai Women’s Health Study

　　[Abstract] Objective: To evaluate the influence of changes in menstrual and reproductive pattern among Chinese women on the temporal trend of breast cancer incidence, we compared the menstrual and reproductive characteristics and incidence rate of breast cancer in different birth cohorts, and examined the associations of menstrual and reproductive factors with the risk of breast cancer in each subgroups using data collected in a population-based cohort study of Chinese women. Methods: The Shanghai Women’s Health Study (SWHS) is a large-scale prospective cohort study of 73,321 women at age 40 to 70 years (birth years from 1926 to 1960) at the time of recruitment (September 1996 and May 2000). All study participants completed a baseline questionnaire, which included detailed information on menstrual and reproductive history. Breast cancer cases were identified by contacting subjects every two years and by record linkage with database of the Shanghai Cancer Registry each year, and were confirmed by medical history review and pathological slides collection. Cox regression model was employed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) related to reproductive factors in the overall set and different birth cohorts. Results: As of the end of 2006, 664 breast cancer cases were confirmed after an average of 8.00 years of follow-up (581,838 person-years of observation). We grouped these women into seven birth cohorts and found that, compared with older birth cohorts, younger birth cohorts had earlier age at menarche, later age at natural menopause, later age at marriage and delivery, longer interval between menarche and first live birth, fewer number of pregnancies and live births, shorter period of lactation and higher age-specific incidence rates of breast cancer. Earlier menarche age, fewer childbirths, later age at first live birth, longer interval between menarche and first live birth, shorter period of lactation and use of hormone replacement therapy (HRT) were associated with increased risk of breast cancer after adjusting for age. Further mutual adjustment attenuated or diminished the associations, remaining number of live birth, age at first live birth, interval between menarche and first birth and HRT as independent risk factors for the disease in the whole cohort. Stratified analysis by birth cohort observed different association patterns among later and earlier birth cohort. While a significantly inverse association was observed for ever having a live birth and number of childbirths in 1926-40’s birth cohort, a does-response relationship was observed for age at first birth and interval between menarche and first birth among 1941-50’s birth cohort. Breastfeeding was linked to the cancer risk only among 1951-60’s birth cohort. These menstrual and reproductive factors generally contributed more to incidence of breast cancer in later than in earlier birth cohort. Conclusions: Our findings suggest that the changes in menstrual and reproductive pattern among Chinese women along birth cohorts may explain some of the increase in breast cancer incidence in this population.