Abstract P5-08-07: Tobacco use, alcohol consumption, and breast cancer somatic genomic alterations

Abstract

Abstract Background: Understanding the molecular influence of epidemiological risk factors can provide insights into breast cancer etiology and progression, and lead to better prevention efforts and treatment guidelines. The link between modifiable breast cancer risk factors and tumor genomic alterations remains unexplored. This study evaluated the association of tobacco use and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30) (1-3), and nine breast cancer driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) (4,5), in a subset of The Cancer Genome Atlas (TCGA). Method: Clinical and genomic data were retrieved from the TCGA database, and breast cancer risk factor information was collected from four TCGA sites; in all, 219 female breast cancer cases were included. Pre-diagnostic tobacco use was defined as never or ever; alcohol consumption was defined as drinkers or non-drinkers. Total SCNV was obtained by summing all segments with ≥|0.2|. TSMB was calculated by summing all significant mutations for each case. SBS signatures were computed using whole exome sequencing data. Analyses were conducted in all tumors (i.e., pooled) and by stratifying according to estrogen receptor (ER) status using multivariate regression, adjusting for co-variables. Results: Tobacco users had higher TSMB compared to non-users (p<0.05 all tumors). Alcohol drinkers had higher SCNV compared to non-drinkers (p<0.05 all tumors and among ER+ tumors). Tobacco use was not associated with any SBS signature. SBS3 signature (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER- disease. No breast cancer driver mutation was associated with tobacco use or alcohol consumption. Conclusion: This study provides preliminary evidence that tobacco use and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. Future larger epidemiological studies are required to confirm these findings.