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Menopause:
doi: 10.1097/GME.0b013e31829e498d
Brief Reports

No association between germline variation in catechol-O-methyltransferase and colorectal cancer survival in postmenopausal women

Passarelli, Michael N. MS, MPH1,2; Newcomb, Polly A. PhD, MPH1,2; Makar, Karen W. PhD1; Burnett-Hartman, Andrea N. PhD, MPH1; Phipps, Amanda I. PhD, MPH1; David, Sean P. MD, DPhil3,4; Hsu, Li PhD1,5; Harrison, Tabitha A. MPH1; Hutter, Carolyn M. PhD1; Duggan, David J. PhD6; White, Emily PhD1,2; Chan, Andrew T. MD, MPH7,8; Peters, Ulrike PhD, MPH1,2

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Abstract

Objective

Sex steroid hormones play a role in colorectal cancer (CRC) development, but little is known about their influence on tumor progression and metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival.

Methods

We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2,458 women with CRC from the Nurses’ Health Study, Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry, VITamins And Lifestyle Study, and Women’s Health Initiative. All four studies participated in the Genetics and Epidemiology of Colorectal Cancer Consortium.

Results

During a median follow-up of 7 years across all studies, there were 799 deaths, including 566 deaths from CRC. Based on multiple comparisons, no associations between single nucleotide polymorphisms and CRC-specific or overall survival reached statistical significance, including the well-characterized Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele, 1.01; 95% CI, 0.90-1.14).

Conclusions

In this large study of women with CRC, we find no evidence that common inherited variation in COMT is associated with survival time after diagnosis.

© 2013 by The North American Menopause Society

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