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

ABSTRACT: 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.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.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).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.

SUBMITTER: Passarelli MN

PROVIDER: S-EPMC3865220 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Passarelli Michael N MN Newcomb Polly A PA Makar Karen W KW Burnett-Hartman Andrea N AN Phipps Amanda I AI David Sean P SP Hsu Li L Harrison Tabitha A TA Hutter Carolyn M CM Duggan David J DJ White Emily E Chan Andrew T AT Peters Ulrike U

Menopause (New York, N.Y.) 20140401 4

<h4>Objective</h4>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.<h4>Methods</h4>We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2, ...[more]

PMID: 23880798

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Project description:ObjectiveCatechol-O-methyltransferase (COMT), a key enzyme in degrading catecholamines associated with the stress response, may influence susceptibility to delirium. Individuals with the COMT (rs4680) Val/Val genotype (designated "warriors") withstand the onset of neuropsychiatric disorders and cognitive decline, whereas individuals with Met/Met and Val/Met genotypes ("nonwarriors") are more susceptible to these conditions. We evaluated whether COMT genotype modifies the established association between acute phase reactant (stress marker) C-reactive protein (CRP) and postoperative delirium.MethodsThis was a prospective cohort study conducted at two academic medical centers. The study involved 547 patients aged 70 or older undergoing major noncardiac surgery. We collected blood, extracted DNA, and performed COMT genotyping using allele-specific polymerase chain reaction assays, considering warriors versus nonwarriors. High plasma CRP, measured on postoperative day 2 using enzyme-linked immunosorbent assay, was defined by the highest sample-based quartile (≥234.12 mg/L). Delirium was determined using the Confusion Assessment Method, augmented by a validated chart review. We used generalized linear models adjusted for age, sex, surgery type, and race/ethnicity, stratified by COMT genotype, to determine whether the association between CRP and delirium differed by COMT.ResultsPrevalence of COMT warriors was 26%, and postoperative delirium occurred in 23%. Among COMT warriors, high CRP was not associated with delirium (relative risk [RR] 1.0, 95% confidence interval [CI] 0.4-2.6). In contrast, among nonwarriors, we found the expected relationship of high CRP and delirium (RR 1.5, 95% CI 1.1-2.2).ConclusionCOMT warriors may be protected against the increased risk of delirium associated with high CRP on postoperative day 2. With further confirmation, COMT genotype may help target interventions for delirium prevention in the vulnerable nonwarrior group.

Dataset Information

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

Publications

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

Similar Datasets

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