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@ARTICLE{Papadimitriou:288088,
author = {N. Papadimitriou and C. Qu and T. A. Harrison and A. M.
Bever and R. M. Martin and K. K. Tsilidis and P. A. Newcomb
and S. N. Thibodeau and C. C. Newton and C. Y. Um and M.
Obón-Santacana and V. Moreno and H. Brenner$^*$ and M.
Mandic$^*$ and J. Chang-Claude$^*$ and M. Hoffmeister$^*$
and A. J. Pellatt and R. E. Schoen and S. Harlid and S.
Ogino and T. Ugai and D. D. Buchanan and B. M. Lynch and S.
B. Gruber and Y. Cao and L. Hsu and J. R. Huyghe and Y. Lin
and R. S. Steinfelder and W. Sun and B. Van Guelpen and S.
H. Zaidi and A. E. Toland and S. I. Berndt and W.-Y. Huang
and E. K. Aglago and D. A. Drew and A. J. French and P.
Georgeson and M. Giannakis and M. Hullar and J. A. Nowak and
C. E. Thomas and L. Le Marchand and I. Cheng and S.
Gallinger and M. A. Jenkins and M. J. Gunter and P. T.
Campbell and U. Peters and M. Song and A. I. Phipps and N.
Murphy},
title = {{B}ody size and risk of colorectal cancer molecular defined
subtypes and pathways: {M}endelian randomization analyses.},
journal = {EBioMedicine},
volume = {101},
issn = {2352-3964},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DKFZ-2024-00342},
pages = {105010},
year = {2024},
abstract = {Obesity has been positively associated with most molecular
subtypes of colorectal cancer (CRC); however, the magnitude
and the causality of these associations is uncertain.We used
Mendelian randomization (MR) to examine potential causal
relationships between body size traits (body mass index
[BMI], waist circumference, and body fat percentage) with
risks of Jass classification types and individual subtypes
of CRC (microsatellite instability [MSI] status, CpG island
methylator phenotype [CIMP] status, BRAF and KRAS
mutations). Summary data on tumour markers were obtained
from two genetic consortia (CCFR, GECCO).A 1-standard
deviation (SD:5.1 kg/m2) increment in BMI levels was found
to increase risks of Jass type
1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio
[OR]: 2.14, $95\%$ confidence interval [CI]: 1.46, 3.13;
p-value = 9 × 10-5) and Jass type
2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR:
2.20, $95\%$ CI: 1.26, 3.86; p-value = 0.005). The magnitude
of these associations was stronger compared with Jass type
4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype
CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD
(SD:13.4 cm) increment in waist circumference increased risk
of Jass type
3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated
(OR 1.73, $95\%$ CI: 1.34, 2.25; p-value = 9 × 10-5) that
was stronger compared with Jass type 4 CRC (p-difference:
0.03). A higher body fat percentage $(SD:8.5\%)$ increased
risk of Jass type 1 CRC (OR: 2.59, $95\%$ CI: 1.49, 4.48;
p-value = 0.001), which was greater than Jass type 4 CRC
(p-difference: 0.03).Body size was more strongly linked to
the serrated (Jass types 1 and 2) and alternate (Jass type
3) pathways of colorectal carcinogenesis in comparison to
the traditional pathway (Jass type 4).Cancer Research UK,
National Institute for Health Research, Medical Research
Council, National Institutes of Health, National Cancer
Institute, American Institute for Cancer Research, Brigham
and Women's Hospital, Prevent Cancer Foundation, Victorian
Cancer Agency, Swedish Research Council, Swedish Cancer
Society, Region Västerbotten, Knut and Alice Wallenberg
Foundation, Lion's Cancer Research Foundation,
Insamlingsstiftelsen, Umeå University. Full funding details
are provided in acknowledgements.},
keywords = {Colorectal cancer (Other) / Mendelian randomization (Other)
/ Molecular subtypes (Other) / Obesity (Other)},
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:38350331},
doi = {10.1016/j.ebiom.2024.105010},
url = {https://inrepo02.dkfz.de/record/288088},
}