Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use

Victoria M. Chia, Polly A. Newcomb, Jeannette Bigler, Libby M. Morimoto, Stephen N Thibodeau, John D. Potter

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk; we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among individuals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (Pinteraction = 0.05): relative to current NSAID users who never smoked, individuals who had both smoked for >40 years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8; 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use.

Original languageEnglish (US)
Pages (from-to)6877-6883
Number of pages7
JournalCancer Research
Volume66
Issue number13
DOIs
StatePublished - Jul 1 2006

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Microsatellite Instability
Microsatellite Repeats
Colorectal Neoplasms
Anti-Inflammatory Agents
Smoking
Non-Steroidal Anti-Inflammatory Agents
Pharmaceutical Preparations
Neoplasms
Population Control
Polyps
Drug Users
Adenoma
Case-Control Studies
Odds Ratio
Confidence Intervals

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use. / Chia, Victoria M.; Newcomb, Polly A.; Bigler, Jeannette; Morimoto, Libby M.; Thibodeau, Stephen N; Potter, John D.

In: Cancer Research, Vol. 66, No. 13, 01.07.2006, p. 6877-6883.

Research output: Contribution to journalArticle

Chia, Victoria M. ; Newcomb, Polly A. ; Bigler, Jeannette ; Morimoto, Libby M. ; Thibodeau, Stephen N ; Potter, John D. / Risk of microsatellite-unstable colorectal cancer is associated jointly with smoking and nonsteroidal anti-inflammatory drug use. In: Cancer Research. 2006 ; Vol. 66, No. 13. pp. 6877-6883.
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