Search PubMed⌕ Search

Biomedical subjects

Charles S Fuchs

Publications and source records attributed to Charles S Fuchs.

At least 55 records · Page 3Linked to original sources
PubMed2005

Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study.

BACKGROUND: Adiponectin is an insulin-sensitizing hormone secreted by adipocytes. Levels of adiponectin are inversely associated with adiposity and insulin resistance. Because both adiposity and insulin resistance have been associated with risk of colorectal cancer, we hypothesized that adiponectin is associated with colorectal carcinogenesis. METHODS: We evaluated the association between adiponectin and colorectal cancer among 18 225 men in the Health Professionals Follow-up Study who provided blood samples in 1994. Between blood collection and January 31, 2002, 179 incident colorectal cancer cases occurred. Each case patient was matched to two control subjects on year of birth and date of blood draw. Information on lifestyle factors and diet was collected using biennial questionnaires and food frequency questionnaires. Logistic regression models were used to estimate relative risks (RRs) and confidence intervals (CIs). All statistical tests were two-sided. RESULTS: We observed a statistically significant inverse association between plasma adiponectin levels and risk of colorectal cancer (for the highest quintile [Q5] versus the lowest quintile [Q1], RR = 0.42, 95% CI = 0.23 to 0.78; P(trend) = .01). The association was only slightly attenuated after adjustment for body mass index (Q5 versus Q1, RR = 0.48, 95% CI = 0.25 to 0.90; P(trend) = .04) or for body mass index and other major risk factors for colorectal cancer (family history, physical activity, multivitamin use, smoking, alcohol, aspirin use, history of endoscopy, dietary calcium, folate, vitamin E, and vitamin D; Q5 versus Q1, multivariable RR = 0.50, 95% CI = 0.26 to 0.97; P(trend) = .08). Relative risks were not linear in any of the analyses; the second quintile had a lower relative risk than the lowest quintile, but further decreases in risk were not evident with increasing levels of adiponectin. CONCLUSIONS: In this prospective nested case-control study, men with low plasma adiponectin levels had a higher risk of colorectal cancer than men with higher levels. More prospective observational studies, particularly in women, and mechanistic studies are required to fully understand the relationship between adiponectin and carcinogenesis.

Adiponectin↗
PubMed2005

Cost-effectiveness projections of oxaliplatin and infusional fluorouracil versus irinotecan and bolus fluorouracil in first-line therapy for metastatic colorectal carcinoma.

BACKGROUND: The results of a randomized comparison study (N9741) showed that oxaliplatin and infusional fluorouracil (FU) (FOLFOX) was superior to the previous standard of care in the United States, irinotecan and bolus FU (IFL), as first-line therapy for patients with metastatic colon carcinoma. The trade-offs between costs and survival for these two regimens have not been explored. METHODS: A post-hoc, incremental cost-effectiveness (ICE) projection using simulated cohorts of patients starting FOLFOX or IFL was tracked for major clinical events, toxicities, and survival. Recurrence and survival risks were based on clinical trial data. Resource use was projected using observed dose intensity, duration of therapy, delays in therapy, and toxicities Grade > 2 in N9741. The frequency, costs, and consequences of second-line therapy were examined. The time frame was 5 years, and the perspective was that of Medicare as a third-party payer. RESULTS: Initial treatment with FOLFOX versus IFL had an average incremental cost of dollars 29,523, a survival benefit of 4.4 months, and an ICE of dollars 80,410 per life year (LY), dollars 111,890 per quality-adjusted LY, and dollars 89,080 per progression-free year. By using the 95% confidence interval for the time to progression observed in N9741, the ICE associated with FOLFOX ranged from dollars 121,220 to dollars 59,250 per LY. In the clinical trial, dose delays and skipped doses were frequent. If progression-free patients were treated without delay for the first year or lifetime, then the ICE for FOLFOX increased to dollars 117,910 and dollars 222,200 per LY, respectively. The ICE increased to dollars 84,780 per LY when the model incorporated a revised IFL schedule with lower early toxicity and similar rates of treatment with second-line regimens. CONCLUSIONS: FOLFOX provided substantial benefits that incurred substantial additional costs. The ICE for FOLFOX fell into the upper range of commonly accepted oncology interventions in the context of the United States healthcare system.

Age Factors↗
PubMed2005

Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer.

PURPOSE: Recently, activating mutations of the epidermal growth factor receptor (EGFR) gene were discovered in non-small cell lung cancers sensitive to gefitinib (ZD1839, an EGFR tyrosine kinase inhibitor) but not in gefitinib-resistant cancers. Abnormalities of EGFR and related pathways may have an effect on responsiveness of advanced colorectal cancer to combination chemotherapy with gefitinib. EXPERIMENTAL DESIGN: We examined patients with previously untreated metastatic colorectal cancer, who were enrolled into two phase I/II trials of combination chemotherapy (irinotecan, leucovorin, and 5-fluorouracil) and daily oral gefitinib. We obtained paraffin tissue blocks of primary tumors from 31 patients, sequenced the EGFR, KRAS, and BRAF genes, and did immunohistochemistry for EGFR, phosphorylated AKT1, p53, p21, and p27. RESULTS: Twelve (39%) of the 31 patients experienced a partial objective response to the therapy. A novel EGFR mutation in exon 18 (c.2170G>A, p.Gly724Ser) was identified in only one patient who did not experience an objective tumor response. EGFR immunohistochemistry was not predictive of responsiveness. In contrast, loss of p21 was associated with a higher response rate to therapy (P = 0.05). Moreover, the response rate among patients whose tumors maintained p21 expression and possessed a mutation in p53 was only 9% (1 of 11, P = 0.005). Overexpression of phosphorylated AKT1 also seemed to predict a trend towards resistance to the therapy. CONCLUSIONS: p21 expression in colorectal cancer, especially in combination with p53 mutation, is a predictor of resistance to the combination chemotherapy with gefitinib. Activating EGFR mutations are rare in colorectal cancer and do not seem to confer sensitivity to gefitinib and chemotherapy.

Adult↗
PubMed2005

Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer.

CONTEXT: Randomized trials of short-term aspirin use for prevention of recurrent colorectal adenoma have provided compelling evidence of a causal relationship between aspirin and colorectal neoplasia. However, data on long-term risk of colorectal cancer according to dose, timing, or duration of therapy with aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) remain limited. OBJECTIVE: To examine the influence of aspirin and NSAIDs in prevention of colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 82 911 women enrolled in the Nurses' Health Study providing data on medication use biennially since 1980 and followed up through June 1, 2000. MAIN OUTCOME MEASURE: Incident colorectal cancer. RESULTS: Over a 20-year period, we documented 962 cases of colorectal cancer. Among women who regularly used aspirin (> or =2 standard [325-mg] tablets per week), the multivariate relative risk (RR) for colorectal cancer was 0.77 (95% confidence interval [CI], 0.67-0.88) compared with nonregular users. However, significant risk reduction was not observed until more than 10 years of use (P< or =.001 for trend). The benefit appeared related to dose: compared with women who reported no use, the multivariate RRs for cancer were 1.10 (95% CI, 0.92-1.31) for women who used 0.5 to 1.5 standard aspirin tablets per week, 0.89 (95% CI, 0.73-1.10) for 2 to 5 aspirin per week, 0.78 (95% CI, 0.62-0.97) for 6 to 14 aspirin per week, and 0.68 (95% CI, 0.49-0.95) for more than 14 aspirin per week (P<.001 for trend). Notably, women who used more than 14 aspirin per week for longer than 10 years in the past had a multivariate RR for cancer of 0.47 (95% CI, 0.31-0.71). A similar dose-response relationship was found for nonaspirin NSAIDs (P = .007 for trend). The incidence of reported major gastrointestinal bleeding events per 1000 person-years also appeared to be dose-related: 0.77 among women who denied any aspirin use; 1.07 for 0.5 to 1.5 standard aspirin tablets per week; 1.07 for 2 to 5 aspirin per week; 1.40 for 6 to 14 aspirin per week; and 1.57 for more than 14 aspirin per week. CONCLUSIONS: Regular, long-term aspirin use reduces risk of colorectal cancer. Nonaspirin NSAIDs appear to have a similar effect. However, a significant benefit of aspirin is not apparent until more than a decade of use, with maximal risk reduction at doses greater than 14 tablets per week. These results suggest that optimal chemoprevention for colorectal cancer requires long-term use of aspirin doses substantially higher than those recommended for prevention of cardiovascular disease, but the dose-related risk of gastrointestinal bleeding must also be considered.

Adult↗
PubMed2005

Patients' perceptions of quality of care for colorectal cancer by race, ethnicity, and language.

PURPOSE: To identify opportunities for improving care, we evaluated patients' perceptions of the quality of their cancer care by race, ethnicity, and language. PATIENTS AND METHODS: We surveyed a population-based cohort of 1,067 patients with colorectal cancer in northern California approximately 9 months after diagnosis. Adjusting for clinical and demographic factors, mean problem scores were analyzed on a 100-point scale for six domains of care. RESULTS: Mean problem scores were highest for health information (47.8), followed by treatment information (32.3), psychosocial care (31.7), coordination of care (21.3), confidence in providers (13.1), and access to cancer care (12.7). In adjusted comparisons with white patients, African American patients reported more problems with coordination of care (difference, 9.8; P < .001), psychosocial care (difference, 7.2; P = .03), access to care (difference, 6.6; P = .03), and health information (difference, 12.5; P < .001). Asian/Pacific Islander patients reported more problems than did white patients with coordination of care (difference, 13.2; P < .001), access to care (difference, 15.5; P < .001), and health information (difference, 12.6; P = .004). Hispanic patients tended to report more problems with coordination of care (difference, 4.4; P = .06), access to care (difference, 5.8; P = .08), and treatment information (difference, 7.0; P = .06). Non-English-speaking white patients reported more problems than other white patients with coordination of care (difference, 21.9; P < .001), psychosocial care (difference, 16.1; P = .009), access to care (difference, 19.8; P = .003), and treatment information (difference, 17.8; P = .002). Non-English-speaking Hispanic patients reported more problems than other Hispanic patients with confidence in providers (difference, 16.9; P = .01). CONCLUSION: Efforts to improve patients' experiences with cancer care should address disparities by race, ethnicity, and language, particularly in coordination of care, access to care, and the provision of relevant information.

Adult↗
PubMed2005

Prospective study of N-acetyltransferase-2 genotypes, meat intake, smoking and risk of colorectal cancer.

Consumption of red meat has been associated with elevated risk of colorectal cancer; however, mechanisms underlying this relationship are not well established. N-acetyltransferase 2 (NAT2) appears to activate carcinogenic heterocyclic amines found in meat as well as cigarette smoke. Genetic variation in this enzyme, associated with rapid acetylation, may modulate the influence of meat intake on cancer risk. We examined the risk of incident colorectal cancer according to NAT2 genotypes, meat intake and smoking in a prospective, nested case-control study among 32,826 women enrolled in the Nurses' Health Study who provided prediagnostic blood specimens. We matched 183 women with colorectal cancer to 443 controls. Although acetylator genotype alone was not associated with the risk of colorectal cancer, women with rapid acetylator genotypes experienced a greater risk associated with intake of > or = 0.5 serving of beef, pork or lamb as a main dish per day compared to intake of less meat (multivariate OR = 3.01; 95% CI = 1.10-8.18). In contrast, among slow acetylators, intake of beef, pork or lamb was not associated with risk of colorectal cancer (multivariate OR = 0.87; 95% CI = 0.35-2.17). The interaction between acetylator genotype and meat intake approached statistical significance (P interaction = 0.07). Moreover, compared to slow acetylators who smoked < or = 35 pack-years and ate < 0.5 serving/day of red meat, the OR for rapid acetylators who smoked > 35 pack-years and ate > or = 0.5 serving/day was 17.6 (95% CI 2.0-158.3). These prospective data suggest that red meat may increase the risk of colorectal cancer, particularly among genetically susceptible individuals. The influence of NAT2 genotype on this association supports a role for heterocyclic amines in mediating the effect of red meat on colorectal carcinogenesis.

Adult↗
PubMed2005

Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of colorectal adenoma in women.

BACKGROUND: Some experimental evidence suggests that iron may play a role in colorectal carcinogenesis, but human data for this role have been conflicting, possibly because of problems related to study design or measurement of iron exposure. We assessed dietary iron intake and genetic and biochemical markers of iron status in a prospective, nested case-control study of women enrolled in the Nurses' Health Study. METHODS: Among 32 826 women who provided a blood specimen, we identified 527 women with colorectal adenoma and 527 matched control subjects who underwent endoscopy but were not diagnosed with adenoma after blood collection. We assessed iron intake, mutations in the HFE gene that are associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma biochemical measures of total body iron, including transferrin saturation and the ratio of the concentrations of transferrin receptors to ferritin. Logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). All statistical tests were two-sided. RESULTS: Women with any HFE gene mutation had higher total body iron stores, as reflected by higher transferrin saturations (P < .001) and lower levels of the ratio of transferrin receptors to ferritin (P = .02), than women with no HFE gene mutation. However, HFE gene mutations were not associated with risk of adenoma (multivariable RR = 1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories showed no associations between adenoma and the extent of transferrin saturation (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60; Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to 1.57; Ptrend = .94). CONCLUSIONS: Although our study used several distinct measures of iron status (i.e., genetic mutations, biochemical markers, and dietary intake) and a nested case-control design, we did not observe a role for iron in the pathogenesis of colorectal neoplasia in women.

Adenoma↗
PubMed2005

Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women.

BACKGROUND: Vitamin B6, whose main circulating form is pyridoxal 5'-phosphate (PLP), is important in one-carbon metabolism, which is critical for DNA synthesis and DNA methylation, both of which are potentially involved in colorectal carcinogenesis. However, no previous epidemiologic studies have directly evaluated the association of plasma PLP with risk for colorectal neoplasia. METHODS: We conducted a prospective nested case-control study of 32,826 female participants of the Nurses' Health Study who provided blood specimens in 1989-1990. From 1989-1990 to 2000 (1998 for adenoma), a total of 194 incident colorectal cancer cases and 410 incident colorectal adenoma cases were identified from medical records. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated using logistic regression. All statistical tests were two-sided. RESULTS: A suggestive inverse association was observed between plasma PLP concentration and risk for colorectal cancer when comparing the highest quartile versus the lowest (RR = 0.56, 95% CI = 0.31 to 1.01; P(trend) = .07); the association of PLP concentration with colon cancer was statistically significant (RR = 0.42, 95% CI = 0.21 to 0.85; P(trend) = .02). Both associations were statistically significant and stronger after controlling for intakes of folate, of multivitamins, and of methionine (for colorectal cancer, RR = 0.48, 95% CI = 0.25 to 0.92; P(trend) = .03; for colon cancer, RR = 0.38, 95% CI = 0.18 to 0.80; P(trend) = .01). Total vitamin B(6) intake was also statistically significantly inversely associated with colon cancer risk (RR = 0.51, 95% CI = 0.27 to 0.97; P(trend) = .007). There was a suggestive inverse association between plasma PLP concentration and advanced distal colorectal adenoma (RR = 0.65, 95% CI = 0.37 to 1.11; P(trend) = .08), but the association with early-stage adenoma was weaker (RR = 0.85, 95% CI = 0.52 to 1.38; P(trend) = .52). CONCLUSIONS: Our results suggest that vitamin B6 may be inversely associated with risk of colorectal neoplasia.

Adenoma↗
PubMed2005

Dietary patterns and pancreatic cancer risk in men and women.

BACKGROUND: Diabetes appears to be associated with the development of pancreatic cancer. Three large prospective cohort studies observed a statistically significant relation between obesity and pancreatic cancer risk. Dietary patterns have been associated with fasting insulin levels and risk of diabetes. To determine whether dietary patterns are associated with pancreatic cancer risk, we analyzed data from two large prospective cohort studies. METHODS: We combined data for men and women to obtain a total of 366 cases of incident pancreatic cancer from a total of 124,672 eligible participants. Dietary data were obtained from food frequency questionnaires in 1986 for men and in 1984 for women. We identified two major dietary patterns, prudent and western, by factor analysis. The prudent pattern was characterized by high fruit and vegetable intake; the western pattern was characterized by high meat and high fat intakes. Multivariable relative risks (RRs) were adjusted for potential confounders, including smoking and body mass index. RESULTS: In the pooled analysis of men and women, no associations were observed between the prudent pattern (RR = 1.32, 95% confidence interval [CI] = 0.66 to 2.63, for highest versus lowest quintile) or the western pattern (RR = 0.91, 95% CI = 0.57 to 1.47, for highest versus lowest quintile) and the risk of pancreatic cancer. Stratifying by body mass index or physical activity did not change the associations. CONCLUSION: Dietary patterns were not associated with the risk of pancreatic cancer in two large cohort studies of men and women.

Adult↗
PubMed2005

Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma.

Genetic variation in the uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) enzyme is associated with impaired metabolism of aspirin. To determine whether polymorphisms in the UGT1A6 enzyme modulate the protective benefit of regular aspirin use on colorectal adenoma, we conducted a prospective, nested case-control study of 1062 women who provided blood specimens and detailed data on aspirin use before undergoing lower endoscopy. All statistical tests were two sided. Although UGT1A6 genotype was not associated with overall adenoma risk (multivariable odds ratio [OR] = 1.10, 95% confidence interval [CI] = 0.85 to 1.41), functional variant genotypes statistically significantly modified the effect of aspirin on adenoma (P(interaction) = .02). Among the 616 women with variant genotypes, regular use of aspirin (two or more standard tablets per week) was associated with a decreased risk of adenoma (multivariable OR for adenoma = 0.66 [95% CI = 0.45 to 0.95], OR = 0.63 [95% CI = 0.43 to 0.91] for 0.5-7 standard tablets per week and OR = 0.41 [95% CI = 0.24 to 0.71] for more than 7 tablets per week; P(trend) = .001). In contrast, among women with wild-type genotypes, regular aspirin use was not associated with a reduced risk nor did they obtain any additional benefit with higher doses (P(trend) = .50). These results were consistent among women with advanced adenomas (P(interaction) = .003). Thus, functional polymorphisms in the UGT1A6 enzyme statistically significantly modify the effect of aspirin on colorectal neoplasia, and certain subsets of the population, defined by genotype, may obtain differential benefit from aspirin chemoprevention.

Adenoma↗
PubMed2005

Coffee, tea, and caffeine consumption and incidence of colon and rectal cancer.

BACKGROUND: Frequent coffee consumption has been associated with a reduced risk of colorectal cancer in a number of case-control studies. Cohort studies have not revealed such an association but were limited in size. We explored the association between consumption of coffee and tea and the incidence of colorectal cancer in two large prospective cohorts of women and men. METHODS: We used data from the Nurses' Health Study (women) and the Health Professionals' Follow-up Study (men). Consumption of coffee and tea and total caffeine intake were assessed and updated in 1980, 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon or rectum was ascertained through 1998. Hazard ratios were calculated using Cox proportional hazards models that adjusted for potential confounders. All tests of statistical significance were two-sided. RESULTS: During almost 2 million person-years of follow-up, 1438 cases of colorectal cancer were observed. Consumption of caffeinated coffee or tea with caffeine or caffeine intake was not associated with the incidence of colon or rectal cancer in either cohort. For both cohorts combined, the covariate-adjusted hazard ratio for colorectal cancer associated with consumption of each additional cup of caffeinated coffee was 0.99 (95% confidence interval [CI] = 0.96 to 1.03). However, participants who regularly consumed two or more cups of decaffeinated coffee per day had a 52% (95% CI = 19% to 71%) lower incidence of rectal cancer than those who never consumed decaffeinated coffee. CONCLUSIONS: Consumption of caffeinated coffee, tea with caffeine, or caffeine was not associated with incidence of colon of rectal cancer, whereas regular consumption of decaffeinated coffee was associated with a reduced incidence of rectal cancer.

Adult↗
PubMed2005

A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States).

OBJECTIVE: We prospectively investigated the independent association of hypertension, thiazide use, body mass index, weight change, and smoking with the risk of renal cell carcinoma among men and women using biennial mailed questionnaires. METHODS: The study population included 118,191 women participating in the Nurses' Health Study and 48,953 men participating in the Health Professionals Follow-up Study. RESULTS: During 24 years of follow-up for women and 12 years for men, 155 and 110 incident cases of renal cell carcinoma were confirmed, respectively. In multivariate models including age, body mass index (BMI), smoking and hypertension, higher BMI was confirmed as a risk factor for women and smoking as a risk factor for men and women. After adjusting for age, updated BMI and smoking, an updated diagnosis of hypertension was associated with renal cell carcinoma (RCC); the relative risk (RR) was 1.9 (95% CI 1.4-2.7) for women and 1.8 (95% CI 1.2-2.7) for men. Based on limited data regarding the use of thiazide diuretics, we did not observe a risk associated with their use, independent of the diagnosis of hypertension. CONCLUSIONS: Diagnosis of hypertension, higher BMI, and increasing pack-years of smoking appear to independently increase the risk of renal cell carcinoma.

Adult↗
PubMed2005

A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma.

Chemotherapy options for esophagogastric adenocarcinoma remain limited. Irinotecan has demonstrated broad activity in a variety of epithelial malignancies. Forty-six patients with previously untreated, measurable, unresectable, or metastatic esophagogastric adenocarcinoma were enrolled. Patients received irinotecan (125 mg/m2 intravenously over 90 min weekly) for 4 consecutive weeks followed by a 2-week rest. Forty-three patients received at least one treatment and were evaluable for response and toxicity. One complete and five partial responses were observed, for an overall response rate of 14% (95% CI, 4-24%). Median survival for all 43 patients was 6.4 months (95% CI, 4.6-8.2 months). Grade 3 to 4 toxicity included 10 patients (23%) with neutropenia, 13 patients (30%) with late diarrhea, 6 patients (14%) with vomiting, and 6 patients (14%) with fatigue. We conclude that although single-agent irinotecan is an active agent for esophagogastric adenocarcinoma, the schedule utilized in this trial is associated with moderate toxicity. When used as a single-agent, a tri-weekly schedule may be preferable for this patient population.

Adenocarcinoma↗
PubMed2005

Sensitive sequencing method for KRAS mutation detection by Pyrosequencing.

Both benign and malignant tumors represent heterogenous tissue containing tumor cells and non-neoplastic mesenchymal and inflammatory cells. To detect a minority of mutant KRAS alleles among abundant wild-type alleles, we developed a sensitive DNA sequencing assay using Pyrosequencing, ie, nucleotide extension sequencing with an allele quantification capability. We designed our Pyrosequencing assay for use with whole-genome-amplified DNA from paraffin-embedded tissue. Assessing various mixtures of DNA from mutant KRAS cell lines and DNA from a wild-type KRAS cell line, we found that mutation detection rates for Pyrosequencing were superior to dideoxy sequencing. In addition, Pyrosequencing proved superior to dideoxy sequencing in the detection of KRAS mutations from DNA mixtures of paraffin-embedded colon cancer and normal tissue as well as from paraffin-embedded pancreatic cancers. Quantification of mutant alleles by Pyrosequencing was precise and useful for assay validation, monitoring, and quality assurance. Our Pyrosequencing method is simple, robust, and sensitive, with a detection limit of approximately 5% mutant alleles. It is particularly useful for tumors containing abundant non-neoplastic cells. In addition, the applicability of this assay for DNA amplified by whole-genome amplification technique provides an expanded source of DNA for large-scale studies.

Colonic Neoplasms↗
PubMed2005

Fiber intake and incidence of colorectal cancer among 76,947 women and 47,279 men.

Prospective cohort studies have consistently found no important link between fiber intake and risk of colorectal cancer. The recent large, prospective European Prospective Investigation into Cancer and Nutrition has challenged this paradigm by suggesting significant protection by high fiber intake. We prospectively investigated the association of fiber intake with the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (76,947 women) and the Health Professionals Follow-up Study (47,279 men). Diet was assessed repeatedly in 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon and rectum was ascertained up to the year 2000. Relative risk estimates were calculated using a Cox proportional hazards model simultaneously controlling for potential confounding variables. During follow-up including 1.8 million person-years and 1,596 cases of colorectal cancer, we found little association with fiber intake after controlling for confounding variables. The hazard ratio for a 5-g/d increase in fiber intake was 0.91 (95% confidence interval, 0.87-0.95) after adjusting for covariates used in the European Prospective Investigation into Cancer and Nutrition study and 0.99 (95% confidence interval, 0.95-1.04) after adjusting for additional confounding variables. Our data from two large prospective cohorts with long follow-up and repeated assessment of fiber intake and of a large number of potential confounding variables do not indicate an important association between fiber intake and colorectal cancer but reveal considerable confounding by other dietary and lifestyle factors.

Adult↗
PubMed2005

Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women.

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.

Adenoma↗
PubMed2005

A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women.

Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.

Adult↗