Format

Send to

Choose Destination
Carcinogenesis. 2016 Jan;37(1):49-55. doi: 10.1093/carcin/bgv160. Epub 2015 Nov 16.

Genetic variants in the mTOR pathway and breast cancer risk in African American women.

Author information

1
Department of Biostatistics, Boston University School of Public Health , Boston, MA 02118 , USA.
2
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute , Buffalo, NY 14263 , USA.
3
Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey , New Brunswick, NJ 08903 , USA.
4
Slone Epidemiology Center at Boston University , Boston, MA 02215 , USA.
5
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill , Chapel Hill, NC 27599 , USA and.
6
Department of Preventive Medicine, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine , Los Angeles, CA 90089 , USA.

Abstract

The phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (mTOR) pathway has been implicated in breast carcinogenesis. However, there has been no large-scale investigation of genetic variants in the mTOR pathway and breast cancer risk. We examined 28847 single-nucleotide polymorphisms (SNPs) in 61 mTOR pathway genes in the African American Breast Cancer Epidemiology and Risk consortium of 3663 cases [1983 estrogen receptor-positive (ER+) and 1098 ER-negative (ER-)] and 4687 controls. Gene-level analyses were conducted using the adaptive rank truncated product (ARTP) test for 10773 SNPs that were not highly correlated (r (2) < 0.8), and SNP-level analyses were conducted with logistic regression. Among genes that were prioritized (nominal P < 0.05, ARTP tests), associations were observed for intronic SNPs TSC2 rs181088346 [odds ratio (OR) of each copy of variant allele = 0.77, 95% confidence interval (CI) = 0.65-0.88 for all breast cancer] and BRAF rs114729114 (OR = 1.53, 95% CI = 1.24-1.91 for all breast cancer and OR = 2.03, 95% CI = 1.50-2.76 for ER- tumors). For ER- tumors, intronic SNPs PGF rs11542848 (OR = 1.38, 95% CI = 1.15-1.66) and rs61759375 (OR = 1.34, 95% CI = 1.14-1.57) and MAPK3 rs78564187 (OR = 1.26, 95% CI = 1.11-1.43) were associated with increased risk. These SNPs were significant at a gene-wide level (Bonferroni-corrected P < 0.05). The variant allele of RPS6KB2 rs35363135, a synonymous coding SNP, was more likely to be observed in ER- than ER+ tumors (OR = 1.18, 95% CI = 1.05-1.31, gene-wide Bonferroni-corrected P = 0.06). In conclusion, specific mTOR pathway genes are potentially important to breast cancer risk and to the ER negativity in African American women.

PMID:
26577839
PMCID:
PMC5006112
DOI:
10.1093/carcin/bgv160
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center