| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Wangefjord, Sakarias Sundström, Magnus Zendehrokh, Nooreldin Lindquist, Kajsa Ericson Nodin, Björn Jirström, Karin Eberhard, Jakob |
| Abstract | Background Activating 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. Methods KRAS 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. Results KRAS 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. Conclusions Results 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. |
| Related Links | https://bsd.biomedcentral.com/counter/pdf/10.1186/2042-6410-4-17.pdf |
| Ending Page | 9 |
| Page Count | 9 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 20426410 |
| DOI | 10.1186/2042-6410-4-17 |
| Journal | Biology of Sex Differences |
| Issue Number | 1 |
| Volume Number | 4 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2013-09-10 |
| Access Restriction | Open |
| Subject Keyword | Human Physiology Endocrinology KRAS mutation Codon 12 Codon 13 BRAF mutation Colorectal cancer Sex Prognosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Gender Studies Endocrinology |
| Journal Impact Factor | 4.9/2023 |
| 5-Year Journal Impact Factor | 6/2023 |
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