ArticleBiology of sex differences2013
Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study.
Article in Biology of sex differences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance).Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Serine-arginine protein kinase 1 (SRPK1) is under-expressed in mucinous colorectal cancer, and may mediate resistance to oxaliplatin.The pharmacogenomics journal · 2025Article
- Sex and gender differences in cancer pathogenesis and pharmacology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Association Between CD147 Expression, RAS Mutational Status, and Local Recurrence in Resected Locally Advanced Rectal Cancer.Cancer medicine · 2025Article
- Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression.Frontiers in immunology · 2023Article
- Clinicopathological Features and Prognostic Value of KRAS/NRAS/BRAF Mutations in Colorectal Cancer Patients of Central China.Current medical science · 2021Article
- Genome-Wide Sex and Gender Differences in Cancer.Frontiers in oncology · 2020Review
- Effect of Tumor Location on Clinicopathological and Molecular Markers in Colorectal Cancer in Eastern China Patients: An Analysis of 2,356 Cases.Frontiers in genetics · 2020Article
- Biomarker-guided therapy for colorectal cancer: strength in complexity.Nature reviews. Clinical oncology · 2020Review
- Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine.Gut · 2018Review
- Prognostic value of the combination of microsatellite instability andCancer management and research · 2018Article
- The clinical impact of tumour-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: A cohort study.International journal of cancer · 2017Article
- Significant association and synergistic adverse prognostic effect of podocalyxin-like protein and epidermal growth factor receptor expression in colorectal cancer.Journal of translational medicine · 2016Article
- Serrated colorectal cancer: Molecular classification, prognosis, and response to chemotherapy.World journal of gastroenterology · 2016Review
- Colon cancer and the epidermal growth factor receptor: Current treatment paradigms, the importance of diet, and the role of chemoprevention.World journal of clinical oncology · 2015Review
- Efficacy of bevacizumab and chemotherapy in the first-line treatment of metastatic colorectal cancer: broadening KRAS-focused clinical view.BMC gastroenterology · 2015Observational
- Tumor LINE-1 methylation level and microsatellite instability in relation to colorectal cancer prognosis.Journal of the National Cancer Institute · 2014Article
- Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions.The American journal of gastroenterology · 2014Review
- Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.Molecular cancer · 2014Article
Corrections and comments
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Authors and funding
7 authors.
Funding
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Abstract
backgroundActivating KRAS and BRAF mutations predict unresponsiveness to EGFR-targeting therapies in colorectal cancer (CRC), but their prognostic value needs further validation. In this study, we investigated the impact of KRAS codons 12 and 13, and BRAF mutations on survival from CRC, overall and stratified by sex, in a large prospective cohort study.
methodsKRAS codons 12 and 13, and BRAF mutations were analysed by pyrosequencing of tumours from 525 and 524 incident CRC cases in The Malmö Diet and Cancer Study. Associations with cancer-specific survival (CSS) were explored by Cox proportional hazards regression, unadjusted and adjusted for age, TNM stage, differentiation grade, vascular invasion and microsatellite instability (MSI) status.
resultsKRAS and BRAF mutations were mutually exclusive. KRAS mutations were found in 191/ 525 (36.4%) cases, 82.2% of these mutations were in codon 12, 17.3% were in codon 13, and 0.5% cases had mutations in both codons. BRAF mutations were found in 78/524 (14.9%) cases. Overall, mutation in KRAS codon 13, but not codon 12, was associated with a significantly reduced CSS in unadjusted, but not in adjusted analysis, and BRAF mutation did not significantly affect survival. However, in microsatellite stable (MSS), but not in MSI tumours, an adverse prognostic impact of BRAF mutation was observed in unadjusted, but not in adjusted analysis. While KRAS mutation status was not significantly associated with sex, BRAF mutations were more common in women. BRAF mutation was not prognostic in women; but in men, BRAF mutation was associated with a significantly reduced CSS in overall adjusted analysis (HR = 3.50; 95% CI = 1.41-8.70), but not in unadjusted analysis. In men with MSS tumours, BRAF mutation was an independent factor of poor prognosis (HR = 4.91; 95% CI = 1.99-12.12). KRAS codon 13 mutation was associated with a significantly reduced CSS in women, but not in men in unadjusted, but not in adjusted analysis.
conclusionsResults from this cohort study demonstrate sex-related differences in the prognostic value of BRAF mutations in colorectal cancer, being particularly evident in men. These findings are novel and merit further validation.
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