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 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 : an official journal of the American Association for Cancer Research 16:1331-1339

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="">