Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women

Niloy Jewel Samadder, 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, Paul John Limburg

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Abstract

OBJECTIVES: Existing data support a modest association between cigarette smoking and incident colorectal cancer (CRC) overall. In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS). METHODS: The IWHS is a population-based cohort study of cancer incidence among 41,836 randomly selected Iowa women, ages 55-69 years of age at enrollment (1986). Exposure data, including cigarette smoking, were obtained by self-report at baseline. Incident CRCs (n=1,233) were ascertained by annual linkage with the Iowa Cancer Registry. Archived tissue specimens from CRC cases recorded through 2002 were recently requested for molecular epidemiology investigations. Tumor KRAS mutation status was determined by direct sequencing of exon 2, with informative results in 507/555 (91%) available CRC cases (342 mutation negative and 165 mutation positive). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between cigarette smoking variables and KRAS-defined CRC subtypes. RESULTS: Multiple smoking variables were associated with increased risk for KRAS mutation-negative tumors, including age at initiation (P=0.02), average number of cigarettes per day (P=0.01), cumulative pack-years (P=0.05), and induction period (P=0.04), with the highest point estimate observed for women who smoked ≥40 cigarettes per day on average (RR=2.38; 95% CI=1.25-4.51; compared with never smokers). Further consideration of CRC subsite suggested that cigarette smoking may be a stronger risk factor for KRAS mutation-negative tumors located in the proximal colon than in the distal colorectum. None of the smoking variables were significantly associated with KRAS mutation-positive CRCs (overall or stratified by anatomic subsite). CONCLUSIONS: Data from this prospective study of older women demonstrate differential associations between cigarette smoking and CRC subtypes defined by KRAS mutation status, and are consistent with the hypothesis that smoking adversely affects the serrated pathway of colorectal carcinogenesis.

Original languageEnglish (US)
Pages (from-to)782-789
Number of pages8
JournalAmerican Journal of Gastroenterology
Volume107
Issue number5
DOIs
StatePublished - May 2012

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Colorectal Neoplasms
Smoking
Mutation
Women's Health
Neoplasms
Tobacco Products
Confidence Intervals
Molecular Epidemiology
Proportional Hazards Models
Self Report
Registries
Exons
Colon
Carcinogenesis
Cohort Studies
Prospective Studies
Incidence
Population

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women. / Samadder, Niloy Jewel; 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; Limburg, Paul John.

In: American Journal of Gastroenterology, Vol. 107, No. 5, 05.2012, p. 782-789.

Research output: Contribution to journalArticle

Samadder, NJ, 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 & Limburg, PJ 2012, 'Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women', American Journal of Gastroenterology, vol. 107, no. 5, pp. 782-789. https://doi.org/10.1038/ajg.2012.21
Samadder, Niloy Jewel ; 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 ; Limburg, Paul John. / Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women. In: American Journal of Gastroenterology. 2012 ; Vol. 107, No. 5. pp. 782-789.
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abstract = "OBJECTIVES: Existing data support a modest association between cigarette smoking and incident colorectal cancer (CRC) overall. In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS). METHODS: The IWHS is a population-based cohort study of cancer incidence among 41,836 randomly selected Iowa women, ages 55-69 years of age at enrollment (1986). Exposure data, including cigarette smoking, were obtained by self-report at baseline. Incident CRCs (n=1,233) were ascertained by annual linkage with the Iowa Cancer Registry. Archived tissue specimens from CRC cases recorded through 2002 were recently requested for molecular epidemiology investigations. Tumor KRAS mutation status was determined by direct sequencing of exon 2, with informative results in 507/555 (91{\%}) available CRC cases (342 mutation negative and 165 mutation positive). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95{\%} confidence intervals (CIs) for associations between cigarette smoking variables and KRAS-defined CRC subtypes. RESULTS: Multiple smoking variables were associated with increased risk for KRAS mutation-negative tumors, including age at initiation (P=0.02), average number of cigarettes per day (P=0.01), cumulative pack-years (P=0.05), and induction period (P=0.04), with the highest point estimate observed for women who smoked ≥40 cigarettes per day on average (RR=2.38; 95{\%} CI=1.25-4.51; compared with never smokers). Further consideration of CRC subsite suggested that cigarette smoking may be a stronger risk factor for KRAS mutation-negative tumors located in the proximal colon than in the distal colorectum. None of the smoking variables were significantly associated with KRAS mutation-positive CRCs (overall or stratified by anatomic subsite). CONCLUSIONS: Data from this prospective study of older women demonstrate differential associations between cigarette smoking and CRC subtypes defined by KRAS mutation status, and are consistent with the hypothesis that smoking adversely affects the serrated pathway of colorectal carcinogenesis.",
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T1 - Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women

AU - Samadder, Niloy Jewel

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

AU - Limburg, Paul John

PY - 2012/5

Y1 - 2012/5

N2 - OBJECTIVES: Existing data support a modest association between cigarette smoking and incident colorectal cancer (CRC) overall. In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS). METHODS: The IWHS is a population-based cohort study of cancer incidence among 41,836 randomly selected Iowa women, ages 55-69 years of age at enrollment (1986). Exposure data, including cigarette smoking, were obtained by self-report at baseline. Incident CRCs (n=1,233) were ascertained by annual linkage with the Iowa Cancer Registry. Archived tissue specimens from CRC cases recorded through 2002 were recently requested for molecular epidemiology investigations. Tumor KRAS mutation status was determined by direct sequencing of exon 2, with informative results in 507/555 (91%) available CRC cases (342 mutation negative and 165 mutation positive). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between cigarette smoking variables and KRAS-defined CRC subtypes. RESULTS: Multiple smoking variables were associated with increased risk for KRAS mutation-negative tumors, including age at initiation (P=0.02), average number of cigarettes per day (P=0.01), cumulative pack-years (P=0.05), and induction period (P=0.04), with the highest point estimate observed for women who smoked ≥40 cigarettes per day on average (RR=2.38; 95% CI=1.25-4.51; compared with never smokers). Further consideration of CRC subsite suggested that cigarette smoking may be a stronger risk factor for KRAS mutation-negative tumors located in the proximal colon than in the distal colorectum. None of the smoking variables were significantly associated with KRAS mutation-positive CRCs (overall or stratified by anatomic subsite). CONCLUSIONS: Data from this prospective study of older women demonstrate differential associations between cigarette smoking and CRC subtypes defined by KRAS mutation status, and are consistent with the hypothesis that smoking adversely affects the serrated pathway of colorectal carcinogenesis.

AB - OBJECTIVES: Existing data support a modest association between cigarette smoking and incident colorectal cancer (CRC) overall. In this study, we evaluated associations between cigarette smoking and CRC risk stratified by KRAS mutation status, using data and tissue resources from the Iowa Women's Health Study (IWHS). METHODS: The IWHS is a population-based cohort study of cancer incidence among 41,836 randomly selected Iowa women, ages 55-69 years of age at enrollment (1986). Exposure data, including cigarette smoking, were obtained by self-report at baseline. Incident CRCs (n=1,233) were ascertained by annual linkage with the Iowa Cancer Registry. Archived tissue specimens from CRC cases recorded through 2002 were recently requested for molecular epidemiology investigations. Tumor KRAS mutation status was determined by direct sequencing of exon 2, with informative results in 507/555 (91%) available CRC cases (342 mutation negative and 165 mutation positive). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs) for associations between cigarette smoking variables and KRAS-defined CRC subtypes. RESULTS: Multiple smoking variables were associated with increased risk for KRAS mutation-negative tumors, including age at initiation (P=0.02), average number of cigarettes per day (P=0.01), cumulative pack-years (P=0.05), and induction period (P=0.04), with the highest point estimate observed for women who smoked ≥40 cigarettes per day on average (RR=2.38; 95% CI=1.25-4.51; compared with never smokers). Further consideration of CRC subsite suggested that cigarette smoking may be a stronger risk factor for KRAS mutation-negative tumors located in the proximal colon than in the distal colorectum. None of the smoking variables were significantly associated with KRAS mutation-positive CRCs (overall or stratified by anatomic subsite). CONCLUSIONS: Data from this prospective study of older women demonstrate differential associations between cigarette smoking and CRC subtypes defined by KRAS mutation status, and are consistent with the hypothesis that smoking adversely affects the serrated pathway of colorectal carcinogenesis.

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