title: Association of type 2 diabetes genetic variants with breast cancer survival among Chinese women.
abstract: OBJECTIVE
  To evaluate whether the genetic susceptibility of T2D was associated with overall survival (OS) and disease-free survival (DFS) outcomes for breast cancer (BC).
  
  
  METHODS
  Included in the study were 6346 BC patients who participated in three population-based epidemiological studies of BC and were genotyped with either GWAS or Exome-chip. We constructed a genetic risk score (GRS) for diabetes using risk variants identified from the GWAS catalog (http://genome.gov/gwastudies) that were associated with T2D risk at a minimum significance level of P ≤ 5.0E-8 among Asian population and evaluated its associations with BC outcomes with Cox proportional hazards models.
  
  
  RESULTS
  During a median follow-up of 8.08 years (range, 0.01-16.95 years), 1208 deaths were documented in 6346 BC patients. Overall, the diabetes GRS was not associated with OS and DFS. Analyses stratified by estrogen receptor status (ER) showed that the diabetes GRS was inversely associated with OS among women with ER- but not in women with ER+ breast cancer; the multivariable adjusted HR was 1.38 (95% CI: 1.05-1.82) when comparing the highest to the lowest GRS quartiles. The association of diabetes GRS with OS varied by diabetes status (P for interaction <0.01). In women with history of diabetes, higher diabetes GRS was significantly associated with worse OS, with HR of 2.22 (95% CI: 1.28-3.88) for the highest vs. lowest quartile, particularly among women with an ER- breast cancer, with corresponding HR being 4.59 (95% CI: 1.04-20.28). No significant association between the diabetes GRS and OS was observed across different BMI and PR groups.
  
  
  CONCLUSIONS
  Our study suggested that genetic susceptibility of T2D was positively associated with total mortality among women with ER- breast cancer, particularly among subjects with a history of diabetes. Additional studies are warranted to verify the associations and elucidate the underlying biological mechanism.
authors: Shanghai Municipal Center for Disease Prevention & Control, 1380 Zhongshan Road West, Shanghai, China.
authors: Ping-Ping
authors: PP
authors: Bao
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, Tennessee, United States of America.
authors: Zhi-Guo
authors: ZG
authors: Zhao
authors: Department of Epidemiology, Shanghai Cancer Institute, 2200/25 Xie Tu Road, Shanghai, China.
authors: Yu-Tang
authors: YT
authors: Gao
authors: Shanghai Municipal Center for Disease Prevention & Control, 1380 Zhongshan Road West, Shanghai, China.
authors: Ying
authors: Y
authors: Zheng
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, Tennessee, United States of America.
authors: Ben
authors: B
authors: Zhang
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, Tennessee, United States of America.
authors: Hui
authors: H
authors: Cai
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, Tennessee, United States of America.
authors: Wei
authors: W
authors: Zheng
authors: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 600, Nashville, Tennessee, United States of America.
authors: Xiao-Ou
authors: XO
authors: Shu
authors: Shanghai Municipal Center for Disease Prevention & Control, 1380 Zhongshan Road West, Shanghai, China.
authors: Wei
authors: W
authors: Lu
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D016019:Survival Analysis; D055815:Young Adult