A Prospective Study of Duration of Smoking Cessation and Colorectal Cancer Risk by Epigenetics-related Tumor Classification

被引：73

作者：

Nishihara, Reiko ^{[1
,2
,3
,4
,5
]}

Morikawa, Teppei ^{[1
,2
]}

Kuchiba, Aya ^{[1
,2
,4
]}

Lochhead, Paul ^{[1
,2
]}

Yamauchi, Mai ^{[1
,2
]}

Liao, Xiaoyun ^{[1
,2
]}

Imamura, Yu ^{[1
,2
]}

Nosho, Katsuhiko ^{[1
,2
]}

Shima, Kaori ^{[1
,2
]}

Kawachi, Ichiro ^{[3
]}

Qian, Zhi Rong ^{[1
,2
]}

Fuchs, Charles S. ^{[1
,2
,6
]}

Chan, Andrew T. ^{[2
,6
,7
]}

Giovannucci, Edward ^{[2
,4
,6
,8
]}

Ogino, Shuji ^{[1
,2
,8
,9
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02215 USA

[4] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA

[5] Osaka Univ, Div Hlth Sci, Grad Sch Med, Osaka, Japan

[6] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA

[7] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA

[8] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA

[9] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

AMERICAN JOURNAL OF EPIDEMIOLOGY | 2013年 / 178卷 / 01期

基金：

美国国家卫生研究院;

关键词：

carcinogen; carcinoma; hypermethylation; epigenomics; molecular epidemiology; public health; tobacco; translational epidemiology; ISLAND METHYLATOR PHENOTYPE; LIFE-STYLE FACTORS; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; POSTMENOPAUSAL HORMONE-THERAPY; DIFFERENTIAL DNA METHYLATION; BODY-MASS INDEX; CIGARETTE-SMOKING; MICROSATELLITE INSTABILITY; ALCOHOL-CONSUMPTION; PROMOTER METHYLATION;

D O I：

10.1093/aje/kws431

中图分类号：

R1 [预防医学、卫生学];

学科分类号：

1004 ; 120402 ;

摘要：

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 (P-trend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (P-trend = 0.25) (P-heterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks). Differential associations between smoking cessation and cancer risks by microsatellite instability (P-heterogeneity = 0.02), DNMT3B expression (P-heterogeneity = 0.03), and BRAF (P-heterogeneity = 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.

引用

页码：84 / 100

页数：17

共 84 条

[61] Diet, lifestyle, and genomic instability in the North Carolina colon cancer study [J].