title: The IRS1 rs2943641 variant and risk of future cancer among morbidly obese individuals.
abstract: BACKGROUND
  Obesity and insulin resistance are risk factors for cancer development. The IRS1 rs2943641 genetic variant has been widely associated with insulin resistance.
  
  
  OBJECTIVE
  The aim of the study was to examine whether the IRS1 rs2943641 associates with cancer incidence in obese individuals.
  
  
  METHODS
  The IRS1 rs2943641 was genotyped in participants from the Swedish Obese Subjects (SOS) study, an intervention trial on the effect of bariatric surgery on mortality and morbidity compared with usual care and in the population-based Malmö Diet and Cancer (MDC) cohort. In both studies, the median follow-up for cancer incidence was about 15 years.
  
  
  METHODS
  Cancer incidence was assessed in both the SOS and the MDC cohorts through national and local registers.
  
  
  RESULTS
  The IRS1 T allele was associated with lower insulin resistance in both the SOS and the MDC studies. A lower cancer incidence was found in T allele carriers from the SOS control group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62-0.96; P = .021) and was restricted to morbidly obese individuals (HR 0.67, 95% CI 0.50-0.91; P = .011). No evidence of such association was detected in the surgery group (interaction P = .005). In the MDC cohort, a nonsignificant tendency for lower cancer incidence in T allele carriers was observed only in morbidly obese individuals. A meta-analysis of morbidly obese individuals (body mass index > 40 kg/m(2)) from the two cohorts strengthened the evidence for the association (HR 0.66, 95% CI 0.50-0.87; P = .004).
  
  
  CONCLUSIONS
  Our results suggest that the T allele of rs2943641 near IRS1 may associate with lower cancer incidence in morbidly obese individuals.
authors: Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, the Sahlgrenska Academy, University of Gothenburg, S-413 45 Gothenburg, Sweden.
authors: Cristina
authors: C
authors: Maglio
authors: Ulrika
authors: U
authors: Ericson
authors: Maria Antonella
authors: MA
authors: Burza
authors: Rosellina Margherita
authors: RM
authors: Mancina
authors: Carlo
authors: C
authors: Pirazzi
authors: Johanna Andersson
authors: JA
authors: Assarsson
authors: Kajsa
authors: K
authors: Sjöholm
authors: Marco Giorgio
authors: MG
authors: Baroni
authors: Per-Arne
authors: PA
authors: Svensson
authors: Tiziana
authors: T
authors: Montalcini
authors: Arturo
authors: A
authors: Pujia
authors: Lars
authors: L
authors: Sjöström
authors: Olov
authors: O
authors: Wiklund
authors: Lena M S
authors: LM
authors: Carlsson
authors: Jan
authors: J
authors: Borén
authors: Marju
authors: M
authors: Orho-Melander
authors: Stefano
authors: S
authors: Romeo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050110:Bariatric Surgery; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D005838:Genotype; D006801:Humans; D015994:Incidence; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D009767:Obesity, Morbid / Q000150:complications* / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D012307:Risk Factors
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins