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.
From the 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2Department of Epidemiology, University of Washington School of Public Health, Seattle, WA; 3Division of General Medical Disciplines, Stanford University School of Medicine, Stanford, CA; 4SRI International, Menlo Park, CA; 5Department of Biostatistics, University of Washington School of Public Health, Seattle, WA; 6Integrated Cancer Genomics Division, Translational Genomics Research Institute, Phoenix, AZ; 7Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; and 8Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.
Received April 18, 2013; revised and accepted May 28, 2013.
Funding/support: This work was supported by the National Institutes of Health, National Cancer Institute (T32CA009168 to M.N.P.; K05CA152715 to P.A.N.; U01CA137088 and R01CA059045 to U.P.; P01CA087969, P50CA127003, and R01CA137178 to A.T.C.; U24CA074794 and R01CA076366 to P.A.N.; and K05CA154337 to E.W.), and National Center for Advancing Translational Sciences (KL2TR000421 to A.N.B.-H.). A.T.C. is a Damon Runyon Clinical Investigator. The Women’s Health Initiative program was funded by the National Institutes of Health, National Heart, Blood, and Lung Institute, through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C.
Financial disclosure/conflicts of interest: S.P.D. has served as a scientific advisor to Genophen Inc.
Address correspondence to: Polly A. Newcomb, PhD, MPH, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109. E-mail: email@example.com