Association Between Smoking and Molecular Subtypes of Colorectal Cancer

被引：14

作者：

Wang, Xiaoliang ^{[1
,2
]}

Amitay, Efrat ^{[3
]}

Harrison, Tabitha A. ^{[1
]}

Banbury, Barbara L. ^{[1
]}

Berndt, Sonja, I ^{[4
]}

Brenner, Hermann ^{[3
,5
,6
]}

Buchanan, Daniel D. ^{[7
,8
,9
,10
]}

Campbell, Peter T. ^{[11
]}

Cao, Yin ^{[12
,13
,14
,15
]}

Chan, Andrew T. ^{[16
,17
,18
,19
]}

Chang-Claude, Jenny ^{[20
,21
]}

Gallinger, Steven J. ^{[22
]}

Giannakis, Marios ^{[23
]}

Giles, Graham G. ^{[24
,25
]}

Gunter, Marc J. ^{[26
]}

Hopper, John L. ^{[7
]}

Jenkins, Mark A. ^{[7
]}

Lin, Yi ^{[1
]}

Moreno, Victor ^{[27
]}

Nishihara, Reiko ^{[23
]}

Newcomb, Polly A. ^{[1
,2
]}

Ogino, Shuji ^{[17
,28
,29
]}

Phipps, Amanda, I ^{[1
,2
]}

Sakoda, Lori C. ^{[1
,30
]}

Schoen, Robert E. ^{[31
]}

Slattery, Martha L. ^{[32
]}

Song, Mingyang ^{[16
,17
,19
,33
]}

Sun, Wei ^{[1
]}

Thibodeau, Steven N. ^{[34
]}

Toland, Amanda E. ^{[35
,36
,37
]}

Van Guelpen, Bethany ^{[38
]}

Woods, Michael O. ^{[39
]}

Hsu, Li ^{[1
]}

Hoffmeister, Michael ^{[3
]}

Peters, Ulrike ^{[1
,2
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98109 USA

[2] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[3] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany

[4] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA

[5] German Canc Res Ctr, Natl Ctr Tumor Dis NCT, Dept Prevent Oncol, Heidelberg, Germany

[6] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany

[7] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Parkville, Vic, Australia

[8] Univ Melbourne, Dept Clin Pathol, Colorectal Oncogen Grp, Parkville, Vic, Australia

[9] Univ Melbourne, Victorian Comprehens Canc Ctr, Ctr Canc Res, Parkville, Vic, Australia

[10] Royal Melbourne Hosp, Genom Med & Family Canc Clin, Melbourne, Vic, Australia

[11] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA

[12] Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA

[13] Barnes Jewish Hosp, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA

[14] Washington Univ, Sch Med, St Louis, MO USA

[15] Washington Univ, Sch Med, Dept Med, Div Gastroenterol, St Louis, MO 63110 USA

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

[17] Harvard Med Sch, Boston, MA 02115 USA

[18] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[19] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA

[20] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany

[21] Univ Med Ctr Hamburg Eppendorf, Univ Canc Ctr Hamburg, Genet Tumour Epidemiol Grp, Hamburg, Germany

[22] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

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

[24] Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia

[25] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia

[26] WHO, Nutr & Metab Sect, Int Agcy Res Canc, Lyon, France

[27] Catalan Inst Oncol IDIBELL, Oncol Data Analyt Program, Barcelona, Spain

[28] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA

[29] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[30] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA

[31] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA

[32] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA

[33] Harvard Univ, Dept Nutr, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[34] Mayo Clin, Div Lab Genet, Dept Lab Med & Pathol, Rochester, MN USA

[35] Ohio State Univ, Comprehens Canc Ctr, Dept Canc Biol, Columbus, OH 43210 USA

[36] Ohio State Univ, Comprehens Canc Ctr, Dept Genet, Columbus, OH 43210 USA

[37] Ohio State Univ, Comprehens Canc Ctr, Dept Internal Med, Columbus, OH 43210 USA

[38] Umea Univ, Dept Radiat Sci, Oncol Unit, Umea, Sweden

[39] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada

来源：

JNCI CANCER SPECTRUM | 2021年 / 5卷 / 04期

基金：

瑞典研究理事会;

关键词：

ISLAND METHYLATOR PHENOTYPE; LIFE-STYLE FACTORS; CIGARETTE-SMOKING; CPG ISLAND; MICROSATELLITE INSTABILITY; DNA METHYLATION; BRAF MUTATION; SERRATED PATHWAY; COLON-CANCER; RISK;

D O I：

10.1093/jncics/pkab056

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Smoking is associated with colorectal cancer (CRC) risk. Previous studies suggested this association may be restricted to certain molecular subtypes of CRC, but large-scale comprehensive analysis is lacking. Methods: A total of 9789 CRC cases and 11 231 controls of European ancestry from 11 observational studies were included. We harmonized smoking variables across studies and derived sex study-specific quartiles of pack-years of smoking for analysis. Four somatic colorectal tumor markers were assessed individually and in combination, including BRAF mutation, KRAS mutation, CpG island methylator phenotype (CIMP), and microsatellite instability (MSI) status. A multinomial logistic regression analysis was used to assess the association between smoking and risk of CRC subtypes by molecular characteristics, adjusting for age, sex, and study. All statistical tests were 2-sided and adjusted for Bonferroni correction. Results: Heavier smoking was associated with higher risk of CRC overall and stratified by individual markers (P-trend <.001). The associations differed statistically significantly between all molecular subtypes, which was the most statistically significant for CIMP and BRAF. Compared with never-smokers, smokers in the fourth quartile of pack-years had a 90% higher risk of CIMP-positive CRC (odds ratio = 1.90, 95% confidence interval = 1.60 to 2.26) but only 35% higher risk for CIMP-negative CRC (odds ratio = 1.35, 95% confidence interval = 1.22 to 1.49; P-difference = 2.1 x 10(-6)). The association was also stronger in tumors that were CIMP positive, MSI high, or KRAS wild type when combined (P-difference <.001). Conclusion: Smoking was associated with differential risk of CRC subtypes defined by molecular characteristics. Heavier smokers had particularly higher risk of CRC subtypes that were CIMP positive and MSI high in combination, suggesting that smoking may be involved in the development of colorectal tumors via the serrated pathway.

引用

页数：10

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