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

Clin Cancer Res. 2010 Feb 15;16(4):1331-9. doi: 10.1158/1078-0432.CCR-09-1877. Epub 2010 Feb 9.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Colorectal Neoplasms / complications*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / complications*
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Mismatch Repair / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Risk Assessment
  • Risk Factors
  • Smoking / adverse effects*