Human Genetics

, Volume 122, Issue 1, pp 41–49 | Cite as

Genetic variation in catechol-O-methyltransferase (COMT) and obesity in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial

  • Sophia S. WangEmail author
  • Lindsay M. Morton
  • Andrew W. Bergen
  • Elizabeth Z. Lan
  • Nilanjan Chatterjee
  • Paul Kvale
  • Richard B. Hayes
  • Stephen J. Chanock
  • Neil E. Caporaso
Original Investigation


Catechol-O-methyltransferase (COMT) is an important modulator in the catabolism of extraneural dopamine, which plays an important role in drug reward mechanisms. It is hypothesized that genetic variations in the COMT gene, which can result in a three to fourfold difference in COMT enzyme activity, may be associated with several reward-motivated behaviors. The aim of our study was to examine the relationship between COMT polymorphisms with smoking, obesity and alcohol. Three single nucleotide polymorphisms (SNPs) in COMT were genotyped in 2,371 participants selected randomly from the screening arm of the PLCO Cancer Screening Trial after stratifying by sex, age, and smoking status. Smoking, obesity, and alcohol consumption were assessed by questionnaire. SNP and haplotype associations were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from conditional logistic regression models, adjusted for race/ethnicity. The COMT Ex4-76C > G (Leu136Leu) polymorphism was statistically significantly associated with individuals who had >30% increases in BMI from ages 20 to 50 years, compared to those with 0–5% increase in BMI (0–5%) over the same age period: (CC is referent; ORCG = 1.42, ORGG = 1.46, P trend = 0.06). By sex, the increased risk was further pronounced among females (ORCG = 1.50, ORGG = 2.10, P trend = 0.03). Consistent with our analyses of single polymorphisms, individuals whose BMI increased >30% from ages 20 to 50 years were more likely than individuals with 0–5% increases in BMI to possess COMT haplotypes [COMT Ex3-104C > T–COMT Ex4-76 C > G–COMT Ex4-12 A > G] that included the variant allele for COMT Ex4-76 C > G: C-G-G (T-C-A is referent: ORC-G- = 1.33, 95% CI 1.01–1.77) and C-G-A (ORC-G-A = 1.79, 95% CI 0.72–4.49). We observed no association between any of the COMT polymorphisms with smoking behavior or alcohol intake. The COMT Ex4-76C > G (Leu136Leu) polymorphism appears to play a role in large increases in BMI. The null association with smoking and alcohol and the pronounced association with increasing BMI among women further implicates COMT’s role in estrogen metabolism as a potentially culpable pathway. Our results support a need for comprehensive evaluation of COMT variations and their functional relevance as COMT may be an important molecular target to evaluate for new treatments regarding obesity.


Smoking Behavior COMT Gene Conditional Logistic Regression Model Catechol Estrogen Cancer Screening Trial 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Body mass index



PLCO Cancer Screening Trial

Prostate, lung, colorectal, and ovarian


Single nucleotide polymorphism


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sophia S. Wang
    • 1
    Email author
  • Lindsay M. Morton
    • 1
  • Andrew W. Bergen
    • 1
  • Elizabeth Z. Lan
    • 1
  • Nilanjan Chatterjee
    • 1
  • Paul Kvale
    • 2
  • Richard B. Hayes
    • 1
  • Stephen J. Chanock
    • 3
  • Neil E. Caporaso
    • 1
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, NIH, DHHSRockvilleUSA
  2. 2.Henry Ford Health SystemDetroitUSA
  3. 3.Core Genotyping Facility, Advanced Technology CorporationNational Cancer Institute, NIH, DHHSGaithersburgUSA

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