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@ARTICLE{Wang:170190,
      author       = {X. Wang and E. Amitay$^*$ and T. A. Harrison and B. L.
                      Banbury and S. I. Berndt and H. Brenner$^*$ and D. D.
                      Buchanan and P. T. Campbell and Y. Cao and A. T. Chan and J.
                      Chang-Claude$^*$ and S. J. Gallinger and M. Giannakis and G.
                      G. Giles and M. J. Gunter and J. L. Hopper and M. A. Jenkins
                      and Y. Lin and V. Moreno and R. Nishihara and P. A. Newcomb
                      and S. Ogino and A. I. Phipps and L. C. Sakoda and R. E.
                      Schoen and M. L. Slattery and M. Song and W. Sun and S. N.
                      Thibodeau and A. E. Toland and B. Van Guelpen and M. O.
                      Woods and L. Hsu and M. Hoffmeister$^*$ and U. Peters},
      title        = {{A}ssociation {B}etween {S}moking and {M}olecular
                      {S}ubtypes of {C}olorectal {C}ancer.},
      journal      = {JNCI cancer spectrum},
      volume       = {5},
      number       = {4},
      issn         = {2515-5091},
      address      = {Oxford},
      publisher    = {Oxford University Press},
      reportid     = {DKFZ-2021-01813},
      pages        = {pkab056},
      year         = {2021},
      abstract     = {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.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.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).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.},
      cin          = {C070 / C120 / HD01 / C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34377935},
      pmc          = {pmc:PMC8346704},
      doi          = {10.1093/jncics/pkab056},
      url          = {https://inrepo02.dkfz.de/record/170190},
}