title: Potentially functional polymorphisms in ATG10 are associated with risk of breast cancer in a Chinese population.
abstract: Autophagy is a cellular process directed at recycling of cellular proteins and removal of intracellular microorganisms, which is important for balancing sources of energy at critical times in development and in response to nutrient stress. It has been reported to be a critical process in cancer initiation and progression. We hypothesized that genetic variants in critical genes of autophagy may be involve in the development of breast cancer. Thus, we systematically screened 14 potentially functional polymorphisms in six autophagy-related genes (ATG3, ATG5, ATG7, ATG10, and ATG12 and LC3) that are core components in autophagosome formation. We conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of these variants with breast cancer risk. We found that rs1864182 and rs10514231 in ATG10 were significantly associated with a decreased risk of breast cancer [odds ratios (OR)=0.77, 95% confidence interval (CI): 0.61-0.96, P=0.023; and OR=0.75, 95% CI: 0.59-0.93, P=0.010, respectively]. Similar protective effects for both loci were observed between subgroups stratified by ages at diagnosis/recruitment, menarche and first live birth, and status of menopause, estrogen receptor (ER) and progesterone receptor (PR). These results suggest that genetic variants in ATG10 may implicate with breast cancer susceptibility in Chinese population. Further large and functional studies are needed to confirm our findings.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Qin
authors.forename: Jialei
authors.initials: J
authors.lastname: Xue
authors.forename: Yisha
authors.initials: Y
authors.lastname: He
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.forename: Jiaping
authors.initials: J
authors.lastname: Chen
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.forename: Xiao'an
authors.initials: X
authors.lastname: Liu
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
mesh_terms: D000328:Adult; D000071183:Autophagy-Related Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; D033921:Vesicular Transport Proteins; C581901:ATG10 protein, human; D044763:Ubiquitin-Conjugating Enzymes
keywords: 95% confidence interval; ATG; Association study; Autophagy; Autophagy-related genes; Breast cancer; CI; ER; ESEs; Estrogen receptor; Exonic splicing enhancers; GWAS; Genome-wide association studies; LD; Linkage disequilibrium; OR; Odds ratios; PR; Polymorphism; Progesterone receptor; SNP; Single nucleotide polymorphism; Susceptibility