Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women

Paul John Limburg, David Limsui, Robert A. Vierkant, Lori S. Tillmans, Alice H. Wang, Charles F. Lynch, Kristin E. Anderson, Amy J. French, Robert W. Haile, Lisa J. Harnack, John D. Potter, Susan L Slager, Thomas Christopher Smyrk, Stephen N Thibodeau, James R Cerhan

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.

Original languageEnglish (US)
Pages (from-to)681-684
Number of pages4
JournalCancer Epidemiology Biomarkers and Prevention
Volume21
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Colorectal Neoplasms
Hormones
Mutation
Confidence Intervals
Women's Health
Therapeutics
Implosive Therapy
Second Primary Neoplasms
Risk Reduction Behavior
Proportional Hazards Models
Codon
Molecular Biology
Exons
Neoplasms
Carcinogenesis
Cohort Studies
Prospective Studies
Population

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women. / Limburg, Paul John; Limsui, David; Vierkant, Robert A.; Tillmans, Lori S.; Wang, Alice H.; Lynch, Charles F.; Anderson, Kristin E.; French, Amy J.; Haile, Robert W.; Harnack, Lisa J.; Potter, John D.; Slager, Susan L; Smyrk, Thomas Christopher; Thibodeau, Stephen N; Cerhan, James R.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 21, No. 4, 04.2012, p. 681-684.

Research output: Contribution to journalArticle

Limburg, PJ, Limsui, D, Vierkant, RA, Tillmans, LS, Wang, AH, Lynch, CF, Anderson, KE, French, AJ, Haile, RW, Harnack, LJ, Potter, JD, Slager, SL, Smyrk, TC, Thibodeau, SN & Cerhan, JR 2012, 'Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women', Cancer Epidemiology Biomarkers and Prevention, vol. 21, no. 4, pp. 681-684. https://doi.org/10.1158/1055-9965.EPI-11-1168
Limburg, Paul John ; Limsui, David ; Vierkant, Robert A. ; Tillmans, Lori S. ; Wang, Alice H. ; Lynch, Charles F. ; Anderson, Kristin E. ; French, Amy J. ; Haile, Robert W. ; Harnack, Lisa J. ; Potter, John D. ; Slager, Susan L ; Smyrk, Thomas Christopher ; Thibodeau, Stephen N ; Cerhan, James R. / Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women. In: Cancer Epidemiology Biomarkers and Prevention. 2012 ; Vol. 21, No. 4. pp. 681-684.
@article{da33c59b4f654ca5b545d030203f900d,
title = "Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women",
abstract = "Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95{\%} confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95{\%} CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95{\%} CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95{\%} CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.",
author = "Limburg, {Paul John} and David Limsui and Vierkant, {Robert A.} and Tillmans, {Lori S.} and Wang, {Alice H.} and Lynch, {Charles F.} and Anderson, {Kristin E.} and French, {Amy J.} and Haile, {Robert W.} and Harnack, {Lisa J.} and Potter, {John D.} and Slager, {Susan L} and Smyrk, {Thomas Christopher} and Thibodeau, {Stephen N} and Cerhan, {James R}",
year = "2012",
month = "4",
doi = "10.1158/1055-9965.EPI-11-1168",
language = "English (US)",
volume = "21",
pages = "681--684",
journal = "Cancer Epidemiology Biomarkers and Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Postmenopausal hormone therapy and colorectal cancer risk in relation to somatic KRAS mutation status among older women

AU - Limburg, Paul John

AU - Limsui, David

AU - Vierkant, Robert A.

AU - Tillmans, Lori S.

AU - Wang, Alice H.

AU - Lynch, Charles F.

AU - Anderson, Kristin E.

AU - French, Amy J.

AU - Haile, Robert W.

AU - Harnack, Lisa J.

AU - Potter, John D.

AU - Slager, Susan L

AU - Smyrk, Thomas Christopher

AU - Thibodeau, Stephen N

AU - Cerhan, James R

PY - 2012/4

Y1 - 2012/4

N2 - Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.

AB - Background: Postmenopausal hormone (PMH) therapy represents a controversial colorectal cancer (CRC) preventive intervention. Because colorectal carcinogenesis is a heterogeneous process, we evaluated associations between PMH therapy and incident CRC in relation to KRAS mutation status in a population-based cohort of older women [Iowa Women's Health Study (IWHS)]. Methods: The IWHS enrolled 41,836 randomly selected women, ages 55 to 69 years, in 1986. PMH therapy and other exposure data were recorded at baseline. Tissue samples from prospectively identified CRC cases (n = 507) were analyzed for somatic KRAS mutations (exon 2, codons 12 and 13). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI). Results: PMH therapy (ever vs. never) was inversely associated with KRAS mutation-negative (RR = 0.83; 95% CI, 0.66-1.06; P = 0.14) and KRAS mutation-positive (RR = 0.82; 95% CI, 0.58-1.16; P = 0.27) tumors, although the observed risk estimates were not statistically significant. When anatomic subsite was additionally considered, the strongest association was found for KRAS mutation-negative, distal colorectal tumors (RR = 0.64; 95% CI, 0.43-0.96; P = 0.03). Conclusions: To our knowledge, we provide the first report of KRAS-defined CRC risks associated with PMHtherapy. These data suggest thatPMHtherapy may reduce CRC risk through mechanisms beyond KRAS mutation status but might provide greater benefits forKRASmutation-negative than mutation-positive tumors (at least in the distal colorectum). Impact: Findings from this prospective cohort study provide novel insights about the molecular biology of PMH therapy-related CRC risk reduction.

UR - http://www.scopus.com/inward/record.url?scp=84859416851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859416851&partnerID=8YFLogxK

U2 - 10.1158/1055-9965.EPI-11-1168

DO - 10.1158/1055-9965.EPI-11-1168

M3 - Article

C2 - 22337533

AN - SCOPUS:84859416851

VL - 21

SP - 681

EP - 684

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

SN - 1055-9965

IS - 4

ER -