title: Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.
abstract: Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, CA.
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Mara Z
authors.initials: MZ
authors.lastname: Vitolins
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Lesley F
authors.initials: LF
authors.lastname: Tinker
authors.affiliation: Center for Health Research, Kaiser Permanente Northwest, Portland, OR.
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.affiliation: Department of Preventive Medicine and Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Epidemiology and Environment Health, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: LaMonte
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN.
authors.forename: Juhua
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Epidemiology and Environment Health, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D017698:Postmenopause; D016016:Proportional Hazards Models
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: diabetes; incidence; invasive cancer; metformin; mortality