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Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE).

Publication ,  Conference
Sehdev, A; Niedzwiecki, D; Venook, AP; Lenz, H-J; Innocenti, F; Mahoney, MR; Shaw, JE; Polite, BN; Hochster, HS; Atkins, JN; Goldberg, R ...
Published in: Journal of Clinical Oncology
February 1, 2018

638 Background: Colorectal cancer (CRC) is a heterogeneous disease with distinct molecular subtypes in part based on RAS mutational status. It is plausible that RAS mutations are differentially distributed between CC and AA and may contribute to poor outcomes in AAs with CRC. Methods: We did a retrospective analysis of CALGB/SWOG 80405 trial patients. We divided the entire cohort into 2 groups: a) Common RAS: mutation in KRAS exon 2, codon 12 or 13; b) Extended RAS: any NRAS mutations or mutation in KRAS except those listed above. We then analyzed these two subgroups for association between RAS mutations and race (3 categories: Caucasian, AA, Others) using chi-square test for univariate analyses and logistic regression for multivariate analysis. We also analyzed the effect of extended RAS testing on prognosis of metastatic CRC by estimating the overall survival (OS) using Kaplan-Meier method and 95% confidence interval (CI). Cox proportional-hazard model was used for multivariate analyses. Results: There were 1729 CRC patients in common RAS group of which 357 (20.6%) had mutations present. Extended RAS group had 621 patients of which 95 (15.5%) had mutations present. There was no significant difference in the rate of common RAS mutations between CC and AA (20.5% vs. 24%, p=0.22). However, extended RAS mutations were significantly more in AA as compared to CC (25% vs. 14%, p=0.02). Multivariate analysis adjusted for age, gender, prior adjuvant chemotherapy and pelvic radiation confirmed higher odds of extended RAS mutation in AA compared to CC (adjusted OR 1.12; 95% CI 1.01-1.23; p=0.02). The median OS in patients with an extended RAS mutation was shorter as compared to those without extended RAS mutation (25.3 vs. 31.9 months; HR 1.26; 95% CI 0.99-1.62; p=0.05). Multivariate analyses adjusted for age, gender, race, prior adjuvant chemotherapy and pelvic radiation showed a trend towards longer OS in patients without extended RAS mutation as compared those with extended RAS mutation (adjusted HR= 1.24, 95% CI, 0.97-0.1.58, p=0.08). Conclusions: Extended RAS mutations are significantly more common in AA as compared to CC. Additionally, presence of extended RAS mutation may confer a poor prognosis in CRC patients.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2018

Volume

36

Issue

4_suppl

Start / End Page

638 / 638

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sehdev, A., Niedzwiecki, D., Venook, A. P., Lenz, H.-J., Innocenti, F., Mahoney, M. R., … O’Neil, B. H. (2018). Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE). In Journal of Clinical Oncology (Vol. 36, pp. 638–638). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2018.36.4_suppl.638
Sehdev, Amikar, Donna Niedzwiecki, Alan P. Venook, Heinz-Josef Lenz, Federico Innocenti, Michelle R. Mahoney, James Edward Shaw, et al. “Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE).” In Journal of Clinical Oncology, 36:638–638. American Society of Clinical Oncology (ASCO), 2018. https://doi.org/10.1200/jco.2018.36.4_suppl.638.
Sehdev A, Niedzwiecki D, Venook AP, Lenz H-J, Innocenti F, Mahoney MR, et al. Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 638–638.
Sehdev, Amikar, et al. “Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE).Journal of Clinical Oncology, vol. 36, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 638–638. Crossref, doi:10.1200/jco.2018.36.4_suppl.638.
Sehdev A, Niedzwiecki D, Venook AP, Lenz H-J, Innocenti F, Mahoney MR, Shaw JE, Polite BN, Hochster HS, Atkins JN, Goldberg R, Mayer RJ, Schilsky RL, Bertagnolli MM, Blanke CD, O’Neil BH. Association of RAS mutations with race in metastatic colorectal cancer: CALGB/SWOG 80405 (ALLIANCE). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2018. p. 638–638.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 1, 2018

Volume

36

Issue

4_suppl

Start / End Page

638 / 638

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences