Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
JAMA Oncol. 2019 Jan 1;5(1):37-44. doi: 10.1001/jamaoncol.2018.4280.
Colorectal cancer (CRC) incidence and mortality among individuals younger than 50 years (early-onset CRC) are increasing. The reasons for such increases are largely unknown, although the increasing prevalence of obesity may be partially responsible.
To investigate prospectively the association between obesity and weight gain since early adulthood with the risk of early-onset CRC.
DESIGN, SETTING, AND PARTICIPANTS: The Nurses' Health Study II is a prospective, ongoing cohort study of US female nurses aged 25 to 42 years at study enrollment (1989). A total of 85 256 women free of cancer and inflammatory bowel disease at enrollment were included in this analysis, with follow-up through December 31, 2011. Validated anthropomorphic measures and lifestyle information were self-reported biennially. Statistical analysis was performed from June 12, 2017, to June 28, 2018.
Current body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), BMI at 18 years of age, and weight gain since 18 years of age.
Relative risk (RR) for incident early-onset CRC.
Among the 85 256 women studied, 114 cases of early-onset CRC were documented (median age at diagnosis, 45 years; interquartile range, 41-47 years) during 1 196 452 person-years of follow-up. Compared with women with a BMI of 18.5 to 22.9, the multivariable RR was 1.37 (95% CI, 0.81-2.30) for overweight women (BMI, 25.0-29.9) and 1.93 (95% CI, 1.15-3.25) for obese women (BMI, ≥30.0). The RR for each 5-unit increment in BMI was 1.20 (95% CI, 1.05-1.38; P = .01 for trend). Similar associations were observed among women without a family history of CRC and without lower endoscopy within the past 10 years. Both BMI at 18 years of age and weight gain since 18 years of age contributed to this observation. Compared with women with a BMI of 18.5 to 20.9 at 18 years of age, the RR of early-onset CRC was 1.32 (95% CI, 0.80-2.16) for women with a BMI of 21.0 to 22.9 and 1.63 (95% CI, 1.01-2.61) for women with a BMI of 23.0 or greater at 18 years of age (P = .66 for trend). Compared with women who had gained less than 5.0 kg or had lost weight, the RR of early-onset CRC was 1.65 (95% CI, 0.96-2.81) for women gaining 20.0 to 39.9 kg and 2.15 (95% CI, 1.01-4.55) for women gaining 40.0 kg or more (P = .007 for trend).
Obesity was associated with an increased risk of early-onset CRC among women. Further investigations among men and to elucidate the underlying biological mechanisms are warranted.
50 岁以下人群（早发性结直肠癌）的结直肠癌发病率和死亡率正在上升。其上升的原因尚不清楚，尽管肥胖的流行率不断增加可能是部分原因。
前瞻性研究自成年早期以来的肥胖和体重增加与早发性结直肠癌风险之间的关系。
设计、地点和参与者：护士健康研究 II 是一项针对美国女性护士的前瞻性、正在进行的队列研究，研究对象年龄在 25 至 42 岁（1989 年）。本分析共纳入了 85256 名在入组时无癌症和炎症性肠病的女性，随访至 2011 年 12 月 31 日。每两年通过自我报告验证人体测量学指标和生活方式信息。统计分析于 2017 年 6 月 12 日至 2018 年 6 月 28 日进行。
当前的体重指数（BMI）（计算方法为体重除以身高的平方）、18 岁时的 BMI 和自 18 岁以来的体重增加。
早发性结直肠癌的相对风险（RR）。
在研究的 85256 名女性中，114 例早发性结直肠癌在 1196452 人年的随访期间被确诊（诊断中位年龄为 45 岁，四分位间距为 41-47 岁）。与 BMI 为 18.5 至 22.9 的女性相比，超重（BMI 为 25.0 至 29.9）的女性多变量 RR 为 1.37（95%CI，0.81-2.30），肥胖（BMI≥30.0）的女性 RR 为 1.93（95%CI，1.15-3.25）。BMI 每增加 5 个单位，RR 为 1.20（95%CI，1.05-1.38；P<0.01 趋势）。在没有结直肠癌家族史和过去 10 年内没有下内窥镜检查的女性中也观察到类似的关联。BMI 在 18 岁时的水平和自 18 岁以来的体重增加都促成了这一观察结果。与 18 岁时 BMI 为 18.5 至 20.9 的女性相比，18 岁时 BMI 为 21.0 至 22.9 的女性早发性结直肠癌的 RR 为 1.32（95%CI，0.80-2.16），BMI 为 23.0 或更高的女性 RR 为 1.63（95%CI，1.01-2.61）（P<0.66 趋势）。与体重增加少于 5.0 公斤或体重减轻的女性相比，体重增加 20.0 至 39.9 公斤的女性早发性结直肠癌的 RR 为 1.65（95%CI，0.96-2.81），体重增加 40.0 公斤或以上的女性 RR 为 2.15（95%CI，1.01-4.55）（P<0.007 趋势）。
肥胖与女性早发性结直肠癌风险增加有关。需要进一步在男性中进行调查，并阐明潜在的生物学机制。
