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BACKGROUND Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic(More)
Aberrant activation of the canonical WNT/beta-catenin pathway occurs in almost all colorectal cancers and contributes to their growth, invasion and survival. Although dysregulated beta-catenin activity drives colon tumorigenesis, further genetic perturbations are required to elaborate full malignant transformation. To identify genes that both modulate(More)
BACKGROUND Choline and betaine are involved in methyl-group metabolism as methyl-group donors; thus, like folate, another methyl-group donor, they may be associated with a reduced risk of colorectal adenomas. No epidemiologic study has examined the association of intake of these nutrients and colorectal adenoma risk. METHODS We investigated the(More)
Prior studies have identified recurrent oncogenic mutations in colorectal adenocarcinoma and have surveyed exons of protein-coding genes for mutations in 11 affected individuals. Here we report whole-genome sequencing from nine individuals with colorectal cancer, including primary colorectal tumors and matched adjacent non-tumor tissues, at an average of(More)
An expression vector was modified to permit the rapid synthesis of purified, 32P-labeled, glutathione S-transferase (GST)-retinoblastoma (RB) fusion proteins. The products were used to screen lambda gt11 expression libraries, from which we cloned a cDNA encoding a polypeptide (RBAP-1) capable of binding directly to a putative functional domain (the pocket)(More)
CONTEXT A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain. OBJECTIVE To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk(More)
Case-control studies suggest that meat and cholesterol intakes may be related to elevated risks of pancreatic cancer. Few prospective studies have examined associations between diet and pancreatic cancer, although in one recent study saturated fat consumption was related to higher risk. In a cohort of US women, the authors confirmed 178 pancreatic cancer(More)
Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of(More)
OBJECTIVE Experimental evidence suggests that 1,25-dihydroxyvitamin D and its precursor, 25-hydroxyvitamin D [25(OH)D], may aid in the prevention of colorectal cancer. We therefore examined risk in relation to plasma concentrations of these vitamin D metabolites. METHODS In a nested case-control study among women in the Nurses' Health Study, we identified(More)
A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we(More)