Smoking and colorectal cancer in lynch syndrome: Results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center

Mala Pande, Patrick M. Lynch, John L. Hopper, Mark A. Jenkins, Steve Gallinger, Robert W. Haile, Loic LeMarchand, Noralane Morey Lindor, Peter T. Campbell, Polly A. Newcomb, John D. Potter, John A. Baron, Marsha L. Frazier, Christopher I. Amos

Research output: Contribution to journalArticle

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Abstract

Purpose: Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI; however, the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design: A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results: Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62; 95% confidence interval (95% CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53; 95% CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (<10 cigarettes per day) and shorter duration of smoking (<10 years) were associated with decreased CRC risk (HR, 0.51; 95% CI, 0.29-0.91 and HR, 0.52; 95% CI, 0.30-0.89, respectively). For former smokers, CRC risk decreased with years since quitting (P trend <0.01). Conclusions: People with Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs.

Original languageEnglish (US)
Pages (from-to)1331-1339
Number of pages9
JournalClinical Cancer Research
Volume16
Issue number4
DOIs
StatePublished - Feb 15 2010

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Hereditary Nonpolyposis Colorectal Neoplasms
Colonic Neoplasms
Registries
Colorectal Neoplasms
Smoking
Neoplasms
Confidence Intervals
Microsatellite Instability
DNA Mismatch Repair
Odds Ratio
Genes
Germ-Line Mutation
Smoke
Tobacco Products
Cluster Analysis
Research Design
Regression Analysis
Parturition
Light
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Smoking and colorectal cancer in lynch syndrome : Results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center. / Pande, Mala; Lynch, Patrick M.; Hopper, John L.; Jenkins, Mark A.; Gallinger, Steve; Haile, Robert W.; LeMarchand, Loic; Lindor, Noralane Morey; Campbell, Peter T.; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Frazier, Marsha L.; Amos, Christopher I.

In: Clinical Cancer Research, Vol. 16, No. 4, 15.02.2010, p. 1331-1339.

Research output: Contribution to journalArticle

Pande, M, Lynch, PM, Hopper, JL, Jenkins, MA, Gallinger, S, Haile, RW, LeMarchand, L, Lindor, NM, Campbell, PT, Newcomb, PA, Potter, JD, Baron, JA, Frazier, ML & Amos, CI 2010, 'Smoking and colorectal cancer in lynch syndrome: Results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center', Clinical Cancer Research, vol. 16, no. 4, pp. 1331-1339. https://doi.org/10.1158/1078-0432.CCR-09-1877
Pande, Mala ; Lynch, Patrick M. ; Hopper, John L. ; Jenkins, Mark A. ; Gallinger, Steve ; Haile, Robert W. ; LeMarchand, Loic ; Lindor, Noralane Morey ; Campbell, Peter T. ; Newcomb, Polly A. ; Potter, John D. ; Baron, John A. ; Frazier, Marsha L. ; Amos, Christopher I. / Smoking and colorectal cancer in lynch syndrome : Results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 4. pp. 1331-1339.
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abstract = "Purpose: Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI; however, the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design: A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results: Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62; 95{\%} confidence interval (95{\%} CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53; 95{\%} CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (<10 cigarettes per day) and shorter duration of smoking (<10 years) were associated with decreased CRC risk (HR, 0.51; 95{\%} CI, 0.29-0.91 and HR, 0.52; 95{\%} CI, 0.30-0.89, respectively). For former smokers, CRC risk decreased with years since quitting (P trend <0.01). Conclusions: People with Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs.",
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T1 - Smoking and colorectal cancer in lynch syndrome

T2 - Results from the Colon Cancer Family Registry and the University of Texas M.D. Anderson Cancer Center

AU - Pande, Mala

AU - Lynch, Patrick M.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Gallinger, Steve

AU - Haile, Robert W.

AU - LeMarchand, Loic

AU - Lindor, Noralane Morey

AU - Campbell, Peter T.

AU - Newcomb, Polly A.

AU - Potter, John D.

AU - Baron, John A.

AU - Frazier, Marsha L.

AU - Amos, Christopher I.

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N2 - Purpose: Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI; however, the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design: A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results: Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62; 95% confidence interval (95% CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53; 95% CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (<10 cigarettes per day) and shorter duration of smoking (<10 years) were associated with decreased CRC risk (HR, 0.51; 95% CI, 0.29-0.91 and HR, 0.52; 95% CI, 0.30-0.89, respectively). For former smokers, CRC risk decreased with years since quitting (P trend <0.01). Conclusions: People with Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs.

AB - Purpose: Lynch syndrome family members with inherited germline mutations in DNA mismatch repair (MMR) genes have a high risk of colorectal cancer (CRC), and cases typically have tumors that exhibit a high level of microsatellite instability (MSI). There is some evidence that smoking is a risk factor for CRCs with high MSI; however, the association of smoking with CRC among those with Lynch syndrome is unknown. Experimental Design: A multicentered retrospective cohort of 752 carriers of pathogenic MMR gene mutations was analyzed, using a weighted Cox regression analysis, adjusting for sex, ascertainment source, the specific mutated gene, year of birth, and familial clustering. Results: Compared with never smokers, current smokers had a significantly increased CRC risk [adjusted hazard ratio (HR), 1.62; 95% confidence interval (95% CI), 1.01-2.57] and former smokers who had quit smoking for 2 or more years were at decreased risk (HR, 0.53; 95% CI, 0.35-0.82). CRC risk did not vary according to age at starting. However, light smoking (<10 cigarettes per day) and shorter duration of smoking (<10 years) were associated with decreased CRC risk (HR, 0.51; 95% CI, 0.29-0.91 and HR, 0.52; 95% CI, 0.30-0.89, respectively). For former smokers, CRC risk decreased with years since quitting (P trend <0.01). Conclusions: People with Lynch syndrome may be at increased risk of CRC if they smoke regularly. Although our data suggest that former smokers, short-term smokers, and light smokers are at decreased CRC risk, these findings need further confirmation, preferably using prospective designs.

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