Po-Hong Liu1, Kana Wu2, Kimmie Ng3, Ann G Zauber4, Long H Nguyen1,5, Mingyang Song1,2, Xiaosheng He1, Charles S Fuchs6, Shuji Ogino7,8,9,10, Walter C Willett2,11, Andrew T Chan1,5,10,11,12, Edward L Giovannucci2,7, Yin Cao1,13,14. 1. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston. 2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 3. Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. 4. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. 5. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston. 6. Yale Cancer Center, New Haven, Connecticut. 7. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 8. Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 9. Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts. 10. Broad Institute of MIT and Harvard, Cambridge, Massachusetts. 11. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 12. Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 13. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri. 14. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri.
Abstract
Importance: 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. Objective: 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. Exposures: 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. Main Outcomes and Measures: Relative risk (RR) for incident early-onset CRC. Results: 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). Conclusions and Relevance: 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.
Importance: 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. Objective: 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. Exposures: 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. Main Outcomes and Measures: Relative risk (RR) for incident early-onset CRC. Results: 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 obesewomen (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). Conclusions and Relevance: 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.
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