Diabetes, metformin use, and colorectal cancer survival in postmenopausal women

Furha Iram Cossor, Lucile L. Adams-Campbell, Rowan T. Chlebowski, Marc J. Gunter, Karen Johnson, Robert E. Martell, Anne McTiernan, Michael S. Simon, Thomas E. Rohan, Robert B. Wallace, Jessica K. Paulus

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Abstract

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n= 84); women with diabetes with no metformin use (n= 128); and women without diabetes (n= 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40-1.38, p= 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61-1.66, p= 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38-1.55, p= 0.47) and for overall survival was 0.86 (95% CI 0.49-1.52; p= 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.

Original languageEnglish (US)
Pages (from-to)742-749
Number of pages8
JournalCancer Epidemiology
Volume37
Issue number5
DOIs
StatePublished - Oct 2013

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Metformin
Colorectal Neoplasms
Survival
Propensity Score
Observational Studies
Women's Health
Proportional Hazards Models
Cause of Death
Cohort Studies

Keywords

  • Colorectal neoplasm
  • Diabetes mellitus
  • Female
  • Metformin
  • Survival rate
  • Treatment outcome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Epidemiology

Cite this

Cossor, F. I., Adams-Campbell, L. L., Chlebowski, R. T., Gunter, M. J., Johnson, K., Martell, R. E., ... Paulus, J. K. (2013). Diabetes, metformin use, and colorectal cancer survival in postmenopausal women. Cancer Epidemiology, 37(5), 742-749. https://doi.org/10.1016/j.canep.2013.04.015

Diabetes, metformin use, and colorectal cancer survival in postmenopausal women. / Cossor, Furha Iram; Adams-Campbell, Lucile L.; Chlebowski, Rowan T.; Gunter, Marc J.; Johnson, Karen; Martell, Robert E.; McTiernan, Anne; Simon, Michael S.; Rohan, Thomas E.; Wallace, Robert B.; Paulus, Jessica K.

In: Cancer Epidemiology, Vol. 37, No. 5, 10.2013, p. 742-749.

Research output: Contribution to journalArticle

Cossor, FI, Adams-Campbell, LL, Chlebowski, RT, Gunter, MJ, Johnson, K, Martell, RE, McTiernan, A, Simon, MS, Rohan, TE, Wallace, RB & Paulus, JK 2013, 'Diabetes, metformin use, and colorectal cancer survival in postmenopausal women', Cancer Epidemiology, vol. 37, no. 5, pp. 742-749. https://doi.org/10.1016/j.canep.2013.04.015
Cossor FI, Adams-Campbell LL, Chlebowski RT, Gunter MJ, Johnson K, Martell RE et al. Diabetes, metformin use, and colorectal cancer survival in postmenopausal women. Cancer Epidemiology. 2013 Oct;37(5):742-749. https://doi.org/10.1016/j.canep.2013.04.015
Cossor, Furha Iram ; Adams-Campbell, Lucile L. ; Chlebowski, Rowan T. ; Gunter, Marc J. ; Johnson, Karen ; Martell, Robert E. ; McTiernan, Anne ; Simon, Michael S. ; Rohan, Thomas E. ; Wallace, Robert B. ; Paulus, Jessica K. / Diabetes, metformin use, and colorectal cancer survival in postmenopausal women. In: Cancer Epidemiology. 2013 ; Vol. 37, No. 5. pp. 742-749.
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abstract = "Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n= 84); women with diabetes with no metformin use (n= 128); and women without diabetes (n= 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95{\%} CI 0.40-1.38, p= 0.67) and to women without diabetes (HR 1.00; 95{\%} CI 0.61-1.66, p= 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95{\%} CI 0.38-1.55, p= 0.47) and for overall survival was 0.86 (95{\%} CI 0.49-1.52; p= 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.",
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AU - Johnson, Karen

AU - Martell, Robert E.

AU - McTiernan, Anne

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KW - Female

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