Phenotypic characteristics of colorectal cancer in BRCA1/2 mutation carriers

Abstract

Mutations in the BRCA1/2 genes were recently shown to be associated with an increased risk for colorectal cancer. We characterized the largest cohort available of BRCA1/2 mutation carriers with colorectal cancer. We analyzed 32 patients with lower gastrointestinal cancers and germline BRCA1/2 mutations from two large academic hospital registries; 91% of patients were of Ashkenazi ancestry, 78% were women, and 62.5% were carriers of BRCA1 gene mutations. A high percentage of colorectal tumors (34.5%) had a mucinous histology and were located atypically in the left colon. Two patients had anal cancer with unusual histology and an additional patient had mucinous small bowel carcinoma. Gene expression analysis showed significant correlation between the gene signatures of left mucinous colorectal cancer and basal-like breast cancer. Our results imply that Ashkenazi BRCA1/2 mutation carriers with colorectal cancer might have unique characteristics with a high rate of left-sided, mucinous histology colorectal cancer, and possibly anal carcinoma. This report suggests a phenotypic influence of defects in DNA repair genes on colorectal tumors.

Fig. 1

Correlations with molecular signatures and the survival of right/left colorectal mucinous or non-mucinous adenocarcinoma tumors. a Boxplot showing the relative correlation of CRC types with the basal-like breast cancer PAM50 vector. Each box represents the second and third quartiles within each group; the center line marks the median and plus signs represent outliers. b Same analysis for the complete basal-like signature. c Kaplan–Meier plots depicting the survival distribution of the four tumor types. For Kaplan–Meier plots, the log rank test was used to assess significance. *P < 0.05, **P < 0.005, Student’s t-test. Ad-L = left-side adenocarcinoma (n = 114), Ad-R = right-side adenocarcinoma (n = 71), Mu-L = left-side mucinous adenocarcinoma (n = 14), Mu-R = right-side mucinous adenocarcinoma (n = 19)