Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
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Cancer Epidemiol. Biomarkers Prev. · Aug 2008
B-vitamin intake, one-carbon metabolism, and survival in a population-based study of women with breast cancer.
Breast cancer is the second leading cause of cancer mortality among women. Given its important role in DNA methylation and synthesis, one-carbon metabolism may affect breast cancer mortality. We used a population-based cohort of 1,508 women with breast cancer to investigate possible associations of dietary intake of B vitamins before diagnosis as well as nine polymorphisms of one-carbon metabolizing genes and subsequent survival. ⋯ Estrogen receptor/progesterone receptor status modified the association between the MTHFR C677T polymorphism and survival (P = 0.05). The survival associations with one-carbon polymorphisms did not differ with the use of chemotherapy, although study power was limited for examining such effect modification. Our results indicate that one-carbon metabolism may be an important pathway that could be targeted to improve breast cancer survival.
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Cancer Epidemiol. Biomarkers Prev. · Jul 2008
Comparative StudyExtensive metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in smokers.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in both unburned tobacco and cigarette smoke. The sum of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides, referred to as total NNAL, is an established urinary biomarker of human NNK uptake. Metabolic activation of NNK to DNA adducts proceeds via alpha-hydroxylation pathways, and 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid) are the principal end products of these pathways in rodents and primates. ⋯ The total amount of [pyridine-D(4)]keto acid plus [pyridine-D(4)]hydroxy acid averaged 4.00 +/- 2.49 nmol/24 h, whereas the average amount of total [pyridine-D(4)]NNAL was 0.511 +/- 0.368 nmol/24 h. The results of this study show for the first time that NNK metabolic activation is a quantitatively significant pathway in smokers, accounting for approximately 86% of total urinary excretion of NNK metabolites. The large interindividual variation in the excreted [pyridine-D(4)]keto acid and [pyridine-D(4)]hydroxy acid among 20 smokers strongly supports our hypothesis that some smokers activate NNK more extensively than others and that the ratio between biomarkers of metabolic activation and detoxification at a given dose of NNK could be a potential indicator of cancer risk.
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Cancer Epidemiol. Biomarkers Prev. · Jun 2008
The Gc2 allele of the vitamin D binding protein is associated with a decreased postmenopausal breast cancer risk, independent of the vitamin D status.
Vitamin D pathway gene polymorphisms may influence breast cancer risk by altering potential anticarcinogenic effects of vitamin D. The association between polymorphisms in the vitamin D binding protein (Gc) and postmenopausal breast cancer risk, with additional focus on the influence of serum 25-hydroxyvitamin D [25(OH)D], the biomarker for vitamin D status in humans, has not been examined thus far. We assessed the combined effects of two known functional polymorphisms in the Gc gene (rs4588 and rs7041), composing the phenotypic alleles Gc1s, Gc1f (combined: Gc1), and Gc2, on postmenopausal breast cancer risk and potential effect modification by 25(OH)D status in a population-based case-control study including 1,402 cases and 2,608 matched controls. ⋯ Gc2-2 genotype was associated with a significantly decreased risk of postmenopausal breast cancer with an odds ratio (95% confidence interval) of 0.72 (0.54-0.96), compared with homozygote Gc1s allele carriers. No interaction between 25(OH)D status and Gc genotype was observed, nor did the association change considerably after adjustment for 25(OH)D status. Our results provide evidence for a serum 25(OH)D-independent effect of Gc2 allele carrier status in postmenopausal breast cancer.
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Cancer Epidemiol. Biomarkers Prev. · May 2008
Aspirin, nonsteroidal anti-inflammatory drugs, and the risks of cancers of the esophagus.
Frequent consumption of aspirin and nonsteroidal anti-inflammatory drugs (NSAID) has been associated with reduced occurrence of cancers of the esophagus, although potential modifying effects of other causal factors remain relatively unexplored. ⋯ Frequent use of aspirin and NSAIDs is associated with reduced occurrence of esophageal cancers, particularly among those with frequent symptoms of gastroesophageal reflux.