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- Borozan, Ivan, et al.
(författare)
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Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis
- 2022
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:1, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
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| 2. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Diabetes mellitus in relation to colorectal tumor molecular subtypes : a pooled analysis of more than 9000 cases
- 2022
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 151:3, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype. In the multinomial logistic regression model, comparing colorectal cancer cases to cancer-free controls, diabetes was positively associated with colorectal cancer regardless of subtype. The highest OR estimate was found for BRAF-mutated colorectal cancer, n = 1086 (ORfully adj: 1.67, 95% confidence intervals [CI]: 1.36-2.05), with an attenuated association observed between diabetes and colorectal cancer without BRAF-mutations, n = 7959 (ORfully adj: 1.33, 95% CI: 1.19-1.48). In the case only analysis, BRAF-mutation was differentially associated with diabetes (Pdifference = .03). For the other markers, associations with diabetes were similar across tumor subtypes. In conclusion, our study confirms the established association between diabetes and colorectal cancer risk, and suggests that it particularly increases the risk of BRAF-mutated tumors.
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