Document Detail

Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women.
MedLine Citation:
PMID:  22349355     Owner:  NLM     Status:  MEDLINE    
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.
N J 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 C Smyrk; Stephen N Thibodeau; James R Cerhan; Paul J Limburg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-21
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  107     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-03     Completed Date:  2012-06-19     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  782-9     Citation Subset:  IM    
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MeSH Terms
Colorectal Neoplasms / etiology*,  genetics*
Middle Aged
Proto-Oncogene Proteins / genetics*
Smoking / adverse effects*
ras Proteins / genetics*
Grant Support
P30 CA086862/CA/NCI NIH HHS; P30 DK084567/DK/NIDDK NIH HHS; R01 CA107333/CA/NCI NIH HHS; R01 CA107333/CA/NCI NIH HHS; R01 CA39742/CA/NCI NIH HHS
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC Proteins

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