title: Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women's Health Initiative: A Longitudinal Study from the United States.
abstract: BACKGROUND
  High body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women.
  
  
  RESULTS
  Participants from the observational study of the Women's Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06-1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much more pronounced in women who never used postmenopausal hormones. This study has limitations because some of the anthropometric information was obtained from retrospective self-reports. Furthermore, data from longitudinal studies with long-term follow-up and repeated anthropometric measures are typically subject to missing data at various time points, which was also the case in this study. Yet, this limitation was partially overcome by using growth curve models, which enabled us to impute data at missing time points for each participant.
  
  
  CONCLUSIONS
  In summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.
authors.affiliation: Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.
authors.forename: Melina
authors.identifier: http://orcid.org/0000-0003-1700-6831
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Department of Epidemiology, School of Medicine, University of California, Irvine, California, United States of America.
authors.forename: Luohua
authors.identifier: http://orcid.org/0000-0002-2281-7260
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California, United States of America.
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Johnson
authors.affiliation: Department of Preventive Medicine, Stony Brook University School of Medicine, Stony Brook, New York, United States of America.
authors.forename: Dorothy S
authors.initials: DS
authors.lastname: Lane
authors.affiliation: Center for Health Research, Kaiser Permanente, Portland, Oregon, United States of America.
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Snively
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors.forename: Mara
authors.initials: M
authors.lastname: Vitolins
authors.affiliation: Faculty of Health Sciences and Social Welfare, University of Haifa, Haifa, Israel.
authors.forename: Oleg
authors.initials: O
authors.lastname: Zaslavsky
authors.affiliation: Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Soerjomataram
authors.affiliation: Department of Epidemiology, School of Medicine, University of California, Irvine, California, United States of America.
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology*; D009765:Obesity / Q000150:complications*; D050177:Overweight / Q000150:complications*; D011247:Pregnancy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D014481:United States; D055815:Young Adult