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

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.

• Authors: Mala Pande, Patrick M Lynch, John L Hopper, Mark A Jenkins, Steve Gallinger, Robert W Haile, Loic LeMarchand, Noralane M Lindor, Peter T Campbell, Polly A Newcomb, John D Potter, John A Baron, Marsha L Frazier, Christopher I Amos
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 4 Pg. 1331-9 (Feb 15 2010) ISSN: 1557-3265 [Electronic] United States
• PMID: 20145170 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Topics

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