A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification

Reiko Nishihara, Teppei Morikawa, Aya Kuchiba, Paul Lochhead, Mai Yamauchi, Xiaoyun Liao, Yu Imamura, Katsuhiko Nosho, Kaori Shima, Ichiro Kawachi, Zhi Rong Qian, Charles S Fuchs, Andrew T Chan, Edward Giovannucci, Shuji Ogino

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Abstract

The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression. Follow-up of 134,204 individuals in 2 US nationwide prospective cohorts (Nurses' Health Study (1980-2008) and Health Professionals Follow-up Study (1986-2008)) resulted in 1,260 incident rectal and colon cancers with available molecular data. Compared with current smoking, 10-19, 20-39, and ≥40 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95% confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (Ptrend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25) (Pheterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (Pheterogeneity = 0.02), DNMT3B expression (Pheterogeneity = 0.03), and BRAF (Pheterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer.
Original languageEnglish
Pages (from-to)84-100
Number of pages17
JournalAmerican Journal of Epidemiology
Volume178
Issue number1
Early online date20 Jun 2013
DOIs
Publication statusPublished - 1 Jul 2013

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CpG Islands
Smoking Cessation
Epigenomics
Colorectal Neoplasms
Prospective Studies
Phenotype
Neoplasms
Microsatellite Instability
Smoking
Molecular Epidemiology
Health
DNA Methylation
Rectal Neoplasms
Oncogenes
Sarcoma
Colonic Neoplasms
Carcinogenesis
Nurses
Regression Analysis
Confidence Intervals

Keywords

  • carcinogen
  • carcinoma
  • hypermethylation
  • epigenomics
  • molecular epidemiology
  • public health
  • tobacco
  • translational epidemiology

Cite this

A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. / Nishihara, Reiko; Morikawa, Teppei; Kuchiba, Aya; Lochhead, Paul; Yamauchi, Mai; Liao, Xiaoyun; Imamura, Yu; Nosho, Katsuhiko; Shima, Kaori; Kawachi, Ichiro; Qian, Zhi Rong; Fuchs, Charles S; Chan, Andrew T; Giovannucci, Edward; Ogino, Shuji.

In: American Journal of Epidemiology, Vol. 178, No. 1, 01.07.2013, p. 84-100.

Research output: Contribution to journalArticle

Nishihara, R, Morikawa, T, Kuchiba, A, Lochhead, P, Yamauchi, M, Liao, X, Imamura, Y, Nosho, K, Shima, K, Kawachi, I, Qian, ZR, Fuchs, CS, Chan, AT, Giovannucci, E & Ogino, S 2013, 'A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification', American Journal of Epidemiology, vol. 178, no. 1, pp. 84-100. https://doi.org/10.1093/aje/kws431
Nishihara, Reiko ; Morikawa, Teppei ; Kuchiba, Aya ; Lochhead, Paul ; Yamauchi, Mai ; Liao, Xiaoyun ; Imamura, Yu ; Nosho, Katsuhiko ; Shima, Kaori ; Kawachi, Ichiro ; Qian, Zhi Rong ; Fuchs, Charles S ; Chan, Andrew T ; Giovannucci, Edward ; Ogino, Shuji. / A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification. In: American Journal of Epidemiology. 2013 ; Vol. 178, No. 1. pp. 84-100.
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abstract = "The effect of duration of cigarette smoking cessation on colorectal cancer risk by molecular subtypes remains unclear. Using duplication-method Cox proportional-hazards regression analyses, we examined associations between duration of smoking cessation and colorectal cancer risk according to status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation, or DNA methyltransferase-3B (DNMT3B) expression. Follow-up of 134,204 individuals in 2 US nationwide prospective cohorts (Nurses' Health Study (1980-2008) and Health Professionals Follow-up Study (1986-2008)) resulted in 1,260 incident rectal and colon cancers with available molecular data. Compared with current smoking, 10-19, 20-39, and ≥40 years of smoking cessation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ratios (95{\%} confidence intervals) of 0.53 (0.29, 0.95), 0.52 (0.32, 0.85), and 0.50 (0.27, 0.94), respectively (Ptrend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25) (Pheterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (Pheterogeneity = 0.02), DNMT3B expression (Pheterogeneity = 0.03), and BRAF (Pheterogeneity = 0.10) status appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, DNMT3B-positive, and BRAF-mutated cancers. These molecular pathological epidemiology data suggest a protective effect of smoking cessation on a DNA methylation-related carcinogenesis pathway leading to CIMP-high colorectal cancer.",
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AU - Liao, Xiaoyun

AU - Imamura, Yu

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KW - carcinoma

KW - hypermethylation

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KW - molecular epidemiology

KW - public health

KW - tobacco

KW - translational epidemiology

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