Document Detail


Cigarette smoking and colorectal cancer risk by KRAS mutation status among older women.
MedLine Citation:
PMID:  22349355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
22672035 - Increased mortality among indigenous persons during and after release from prison in ne...
22818255 - Ethnic differences in the use of intrapartum epidural analgesia.
22403395 - Modelling coronary heart disease mortality in northern ireland between 1987 and 2007: b...
22338765 - Association of the psychological distress and cardiovascular risk behaviors, conditions...
22868545 - Migraine in women.
25122725 - Mortality in patients with giant cell arteritis.
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Colorectal Neoplasms / etiology*,  genetics*
Female
Humans
Middle Aged
Mutation*
Proto-Oncogene Proteins / genetics*
Risk
Smoking / adverse effects*
ras Proteins / genetics*
Grant Support
ID/Acronym/Agency:
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
Chemical
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; EC 3.6.5.2/ras Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  An investigation and pathological analysis of two fatal cases of cadmium poisoning.
Next Document:  Neural network of primary focal dystonia by an anatomic likelihood estimation meta-analysis of gray ...