Incident Colon Research Articles

No association between phosphatase and tensin homolog genetic polymorphisms and colon cancer

To investigate the association between single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homolog (PTEN) tumor suppressor gene and risk of colon cancer. We utilized a population-based case-control study of incident colon cancer individuals (n = 421) and controls (n = 483) aged > or = 30 years to conduct a comprehensive tagSNP association analysis of the PTEN gene. None of the PTEN SNPs were statistically significantly associated with colon cancer when controlled for age, gender, and race, or when additionally adjusted for other known risk factors (P > 0.05). Haplotype analyses similarly showed no association between the PTEN gene and colon cancer. Our study does not support PTEN as a colon cancer susceptibility gene.

The Identification of Lynch Syndrome in British Columbia

To determine the prevalence of Lynch syndrome mutations in a Canadian hereditary cancer clinic population, and to determine the effectiveness of the program's referral criteria and testing algorithm. A retrospective chart review of all patients who were referred for and received genetic counselling at the BC Cancer Agency's Hereditary Cancer Program for a family history of colon cancer from August 1, 2004, to September 1, 2006, was performed. Charts were reviewed for referral criteria met, cancer history, whether testing was offered and the outcome of testing. Lynch syndrome was confirmed or highly suspected in 14.3% of index test patients (eight of 56) by the identification of a deleterious mutation or variant likely to be deleterious in either of the hMLH1 or hMSH2 mismatch repair genes. In the program, the two most effective criteria were a personal diagnosis of two or more primary Lynch syndrome-related cancers (one diagnosed at younger than 50 years of age) or two first-degree relatives with a Lynch syndrome-related cancer (both diagnosed at younger than 50 years of age). The respective positive predictive values of these two criteria were calculated to be 66.7% (95% CI 40% to 93%) and 58.3% (95% CI 30.4% to 86.2%). The Hereditary Cancer Program developed and successfully implemented an approach that selected individuals at risk for Lynch syndrome with a significant pretest probability of mutation of 14.3%. Improved ascertainment of families with Lynch syndrome will require greater physician awareness of referral criteria, program advances in the testing algorithm and a population-based approach to screening incident colon cancers.

Dietary Vitamin D Intake and Cancers of the Colon and Rectum: A Case-Control Study in Italy

Epidemiologic evidence indicates that vitamin D is inversely associated with risk of colon or rectal cancer or both. Using data from a case-control study conducted in Italy between 1992 and 1996, we examined the relation between dietary intake of vitamin D and colon and rectal cancer risk. The study population comprised patients with incident colon cancer (n = 1,225) or rectal cancer (n = 728) and 4,154 hospital controls. Odds ratios (OR) and 95% confidence intervals (CI) according to deciles of vitamin D intake were estimated by multiple logistic regression. In addition, we adjusted for intensity of sunlight exposure through stratification by geographic region of residence, and we computed ORs separately by anatomic subsite within the colon. Adjusted ORs for colon cancer were seen to decrease after the 5th decile of vitamin D intake and reached 0.69 (95% CI = 0.50–0.96) for the 9th and 10th deciles, reflecting a statistically significant inverse trend. The inverse association appeared to be somewhat more pronounced for the proximal than the distal colon and was similar among strata of geographic region and calcium intake. Rectal cancer was unrelated to vitamin D intake in this population. In conclusion, we observed an inverse association between dietary vitamin D intake and colon cancer risk among those with the highest intake levels, which was somewhat unexpected given that these levels were still substantially below the levels considered optimal for colon cancer prevention.

A Prospective Study of Dietary Folate and Vitamin B and Colon Cancer According to Microsatellite Instability and KRAS Mutational Status

Sporadic microsatellite instability (MSI)-high colon cancers are positively associated with MLH1 promoter methylation and inversely with KRAS mutation. One-carbon metabolism is critical for methylation reactions and nucleotide biosynthesis, but the influence of dietary one-carbon nutrients such as folate and B vitamins on molecular changes in colon cancer is not known. Using the database of two independent prospective cohort studies (88,691 women and 47,371 men), we examined the relation between dietary intake of one-carbon nutrients and the incidence of microsatellite instability and KRAS mutation in 669 incident colon cancers. The overall inverse association between folate and colon cancer did not differ significantly according to MSI status [relative ratio (RR), 0.79; 95% confidence interval (95% CI), 0.60-1.03 for microsatellite stable/MSI-low colon cancers; and RR, 0.61, 95% CI, 0.37-1.02 for MSI-high colon cancers; P(heterogeneity)=0.53] or KRAS status (RR, 0.66; 95% CI, 0.49-0.87 for KRAS wild-type colon cancers; and RR, 1.05; 95% CI, 0.68-1.61 for KRAS mutated colon cancers; P(heterogeneity)=0.12), although our analyses had limited power to preclude an effect of folate on KRAS wild-type colon cancers. Similarly, high vitamin B(6) or B(12) intake was inversely associated with colon cancers, regardless of MSI or KRAS status. No significant effect of methionine intake or alcohol consumption was observed for colon cancers with MSI high or KRAS mutation. In conclusion, the influence of dietary one-carbon nutrient intake on colon cancer risk does not seem to differ according to MSI or KRAS mutational status.

Similar reductions in the risk of human colon cancer by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors

BackgroundEpidemiologic and laboratory investigations suggest that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have chemopreventive effects against colon cancer perhaps due at least in part to their activity against cyclooxygenase-2 (COX-2), the rate-limiting enzyme of the prostaglandin cascade.MethodsWe conducted a case control study of colon cancer designed to compare effects of selective and non-selective COX-2 inhibitors. A total of 326 incident colon cancer patients were ascertained from the James Cancer Hospital, Columbus, Ohio, during 2003–2004 and compared with 652 controls with no history of cancer and matched to the cases at a 2:1 ratio on age, race, and county of residence. Data on the past and current use of prescription and over the counter medications and colon cancer risk factors were ascertained using a standardized risk factor questionnaire. Effects of COX-2 inhibiting agents were quantified by calculating odds ratios (OR) and 95% confidence intervals.ResultsResults showed significant risk reductions for selective COX-2 inhibitors (OR = 0.31, 95% CI = 0.16–0.57), regular aspirin (OR = 0.33, 95% CI = 0.20–0.56), and ibuprofen or naproxen (0.28, 95% CI = 0.15–0.54). Acetaminophen, a compound with negligible COX-2 activity and low dose aspirin (81 mg) produced no significant change in the risk of colon cancer.ConclusionThese results suggest that both non-selective and selective COX-2 inhibitors produce significant reductions in the risk of colon cancer, underscoring their strong potential for colon cancer chemoprevention.

Folate and Vitamin B6 Intake and Risk of Colon Cancer in Relation to p53 Expression

Considerable evidence suggests that a low-folate diet increases the risk of colorectal cancer, although the results of a recent randomized trial indicate that folate supplementation may not reduce the risk of adenoma recurrence. In laboratory models, folate deficiency appears to induce p53 mutation. We immunohistochemically assayed p53 expression in paraffin-fixed colon cancer specimens in a large prospective cohort of women with 22 years of follow-up to examine the relationship of folate intake and intake of other one-carbon nutrients to risks by tumor p53 expression. A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (P(heterogeneity) = .01). Compared with women reporting folate intake <200 microg/day, the multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were 0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299 microg/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 microg/day, and 0.54 (95% CI, 0.35-0.83) for women who consumed >or=400 microg/day. In contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95% CI, 0.73-1.51; comparing >or=400 with <200 microg/day). Similarly, high vitamin B(6) intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but had no effect on p53 wild-type tumors. We found that low folate and vitamin B(6) intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors.

Are we use of chemotherapy for elderly stage III colon cancer patients? An analysis from the Cancer Care Outcomes & Research Surveillance Consortium (CanCORS)

6500 Background: Multiple studies have documented lower rates of use of adjuvant therapy for colorectal cancer with increasing patient age despite evidence from RCTs that older patients (pts) experience similar benefits from treatment. This suggests the concern that pts treated on those trials may not be representative of the typical elderly colorectal cancer patient. We therefore examined the outcomes of adjuvant therapy for colorectal cancer in a nationally representative sample of pts treated in the routine care setting. Methods: As part of the CanCORS observational cohort study, we assessed important clinical morbid events (CME) recorded in the medical records (e.g., sepsis, myocardial infarction) for a population-based sample of 705 patients with incident colon cancer from multiple U.S. regions. We used Poisson models with propensity score to calculate adjusted mean number of CME events summed, from colectomy to 15 months post- diagnosis, by age. We adjusted for demographics, site, survey type, comorbidity, pre-dx health status, clinical complications during the pre- and post-op periods prior to chemo use; and then for 1st 5FU dose and route, chemo dose reduction, and chemo duration. Results: Overall, of 705 stage III pts, the prevalence of CME was none for 67%, one for 22%, and ≥two for 11% with a mean of 0.49 (SD 0.91) CME following surgery to the end of study. The adjusted mean number of CME are not worse for older pts, even after adjustment for 1st chemo dose and route, dose reduction and chemo duration. Conclusions: Although elderly patients are much less likely than younger patients to receive adjuvant chemotherapy for stage III colon cancer, those who receive chemotherapy, experience similar rates of clinical morbid events. Age Categories (years) Adjusted Mean Number of Clinical Morbid Events (n=705) Pts Receiving Chemo (N=517) No Chemo (n=188) Without adjustment for chemo dose After adjustment for chemo dose 21–55 (n=79) 0.71 (n=8) 0.46 0.45 56–65 (n=153) 0.40 (n=19) 0.54 0.53 66–75 (n=180) 0.48 (n=38) 0.49 0.51 >75 (n=293) 0.38 (n=123) 0.47 0.48 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration National Cancer Institute

MicroRNA Expression Profiles Associated With Prognosis and Therapeutic Outcome in Colon Adenocarcinoma

MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome. To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome. MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort. MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. RESULTS Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome. Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome.

Patterns of care among veterans with colon cancer: Insights from California SEER, Medicare and VA-linked data

6586 Background: U.S. veterans have been shown to be a vulnerable population with high cancer rates, yet practice pattern information is lacking. Linkage of cancer registry, Medicare, and VA data provides a more complete view of health status and healthcare received among veterans with cancer. Methods: As part of a national study, a retrospective cohort of incident colon cancer patients from the California Cancer Registry data, who were = 66 years old and eligible to use VA and Medicare between 1999 and 2001, were followed for three years through 2004. We examined practice patterns for stages I-IV colon cancer, specifically, surgery and use of chemotherapy, and trends in one-year mortality using descriptive and multivariate regression models. Results: Among 633 veterans with colon cancer, 93% were male; 16% were African American; 28% were diagnosed at a VA facility compared to 72% at a Medicare facility, and 553 (87%) had colectomy. One year mortality rate was 29%. Among the 553 colectomy patients, prevalence of chemotherapy use, according to stage was 8%, 27%, 61% and 52% for stages I-IV, respectively (p-value &lt;0.0001). Regression analyses of factors affecting whether chemotherapy was received revealed that Stage III patients were most likely to receive adjuvant chemotherapy (Odds Ratio (OR) 19.80, 95% Confidence Interval (CI): 9.68–40.50). However stage II and stage IV patients were also highly likely to receive chemotherapy following surgery (OR: 4.41 CI: 2.18–8.91 and OR: 13.21; CI: 6.01–29, respectively). Patients =76 years and those =86 years were less likely to receive chemotherapy following surgery (OR: 0.61, CI: 0.40–0.94 and OR: 0.25, CI: 0.094–0.64, respectively) compared to patients 66–75 years. Patients with Charlson Comorbidity Score of 2 or greater were less likely to receive chemotherapy (OR: 0.49; CI: 0.29–0.84). Treating facility (VA or Medicare), did not affect chemotherapy use. Conclusions: Among veterans with colon cancer in California, older patients were less likely to receive chemotherapy even when stage and comorbidity status were considered. Efforts focused on improving guideline consistent adjuvant chemotherapy use among older veterans with stage III colon cancer across treating facilities may yield the greatest benefit. No significant financial relationships to disclose.

Genetic polymorphisms in one-carbon metabolism: associations with CpG island methylator phenotype (CIMP) in colon cancer and the modifying effects of diet

This study investigated associations between CpG island methylator phenotype (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism and thus, potentially the provision of methyl groups and risk of colon cancer. Data from a large, population-based case-control study (916 incident colon cancer cases and 1,972 matched controls) were used. Candidate polymorphisms in methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP- or CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16 and MLH1. The influence of specific dietary factors (folate, methionine, vitamin B(12) and alcohol) on these associations was also analyzed. We hypothesized that polymorphisms involved in the provision of methyl groups would be associated with CIMP+ tumors (two or more of five markers methylated), potentially modified by diet. Few associations specific to CIMP+ tumors were observed overall, which does not support the hypothesis that the provision of methyl groups is important in defining a methylator phenotype. However, our data suggest that genetic polymorphisms in MTHFR 1,298A > C, interacting with diet, may be involved in the development of highly CpG-methylated colon cancers. AC and CC genotypes in conjunction with a high-risk dietary pattern (low folate and methionine intake and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3-3.4 versus AA/high risk; P-interaction = 0.03). These results provide only limited support for a role of polymorphisms in one-carbon metabolism in the etiology of CIMP colon cancer.

Body Mass and Colorectal Cancer Risk in the NIH-AARP Cohort

In most studies, body mass index (BMI) has been associated with increased risk of colorectal or colon cancer in men, but the relation is weaker and less consistent for women, possibly because of interactions with age or hormone replacement therapy. The authors examined the relation between BMI and colorectal cancer incidence in a large, prospective US cohort of 307,708 men and 209,436 women from the NIH-AARP Diet and Health Study. During follow-up of the cohort from 1995 to 2000, 2,314 cases of colorectal cancer were observed in men and 1,029 in women. BMI was related to increased risk of incident colon cancer, but not rectal cancer, for both men and women. For men, relative risks of colon cancer for a BMI of 18.5-<23, 23-<25, 25-<27.5, 27.5-<30, 30-<32.5, 32.5-<35, 35-<40, and > or = 40 kg/m(2) were 1.0 (referent), 1.11, 1.22, 1.44, 1.53, 1.57, 1.71, and 2.39, respectively (95% confidence interval: 1.59, 3.58; p-trend < 0.0005). Corresponding relative risks for women were 1.0, 1.20, 1.29, 1.31, 1.28, 1.13, 1.46, and 1.49 (95% confidence interval: 0.98, 2.25; p-trend = 0.02). BMI was related to colon cancer risk for younger (aged 50-66 years) but not older (aged 67-71 years) women. The association was not modified by hormone replacement therapy in women or physical activity in men or women.

Thymidylate synthase polymorphisms and colon cancer: Associations with tumor stage, tumor characteristics and survival

Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. We investigated the role of functional polymorphisms in the TS 5'-UTR promoter enhancer region (TSER, 3 or 2 repeats of a 28-bp sequence) and the 3'-UTR (1494delTTAAAG) and their association with colon tumor characteristics, including tumor stage and acquired mutations in p53, Ki-ras and microsatellite instability. Data from a population-based incident case-control colon cancer study in northern California, Utah and Minnesota (1,206 cases, 1,962 controls) was analyzed using unordered polytomous logistic regression models. In both men and women, individuals with variant TS alleles were at reduced risk of having an advanced stage tumor (metastatic disease: OR = 0.35, 95% CI: 0.2-0.6 vs. wildtype TSER and 3'-UTR). Stage-adjusted survival did not differ by genotype. Men with 1 or 2 variant alleles in both the TSER and 3'-UTR genotypes had a 50% reduced risk of a p53-positive tumor (OR = 0.5, 95% CI: 0.3-0.9 vs. homozygous wildtype TSER and 3'-UTR). Women with 1 or 2 variant alleles for either the TSER or 3'-UTR polymorphism had reduced risk of having any colon tumor that did not vary by mutation status. This study provides some support for associations between TS genotype and colon cancer tumor characteristics.

Sizing up the association between body fat and colorectal cancer risk

Sizing up the association between body fat and colorectal cancer risk

Physical activity and risk of colon cancer in a cohort of Danish middle-aged men and women

To investigate the effects of occupational activity and leisure time activity on incident colon cancer risk in a Danish middle-aged population. In the cohort, Diet, Cancer and Health, which included 28,356 women and 26,122 men aged 50-64 years at baseline, 140 women and 157 men were diagnosed with colon cancer from 1993 to 2003. The associations between occupational and leisure time activity in terms of a MET-score and the single activities, sports, cycling, walking, gardening, housework and do-it-yourself work, and incident colon cancer were investigated. Leisure time activity was investigated in two ways using the Cox proportional hazards model: by comparison of active versus non-active and by investigating a possible dose-response relationship while allowing a separate association for non-active individuals. No associations were found between risk of colon cancer and occupational activity, MET-hours per week of total leisure time activity, residuals from a regression of each activity on the total MET-hours or the time spent on any of the six types of leisure time activities. However, a borderline significant association was found with the number of activities in which the participants were active. For each additional activity IRR = 0.87 (0.76-1.00) for women and IRR = 0.88 (0.78-1.00) for men. Our data do not support the evidence of an inverse association between colon cancer risk and occupational activity or leisure time activity, but avoiding a sedentary lifestyle by participating in different activities may reduce colon cancer risk.

Microsatellite Instability in Interval Colon Cancers

Colon cancers that develop after a complete colonoscopy may be the result of "failure of colonoscopy" or rapid tumor growth. Tumors that develop via the mismatch repair gene pathway demonstrate rapid tumor growth. The aim of this study was to determine if interval colon cancers were more likely than noninterval cancers to result from the loss of function of mismatch repair genes and hence demonstrate microsatellite instability (MSI). We searched our institution's cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched in a 1:2 ratio by age and sex to patients with noninterval cancers (defined as colon cancers diagnosed on a patient's first recorded colonoscopy). Archived cancer specimens for all subjects were retrieved and tested for MSI. Of the 993 colon cancers diagnosed during the study period, 51 (5.1%) were identified as an interval cancer, and 112 subjects with noninterval cancer served as a comparison group. Study subjects were almost all men. MSI was found in 30.4% of interval cancers compared with 10.3% of noninterval cancers (P = .003). After adjusting for age, interval cancers were 3.7 times more likely to show MSI than noninterval cancers (95% confidence interval, 1.5-9.1). This association was strongest for tumors located in the distal colon (odds ratio, 17.5; P = .008). No difference in TNM stage at diagnosis, histologic type or grade, or 5-year survival was found between groups. Interval colon cancers were almost 4 times as likely as noninterval colon cancers to be associated with mismatch repair gene dysfunction.

Diet and lifestyle factor associations with CpG island methylator phenotype and BRAF mutations in colon cancer

It has been proposed that dietary factors such as folate, alcohol and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large population-based case-control study of incident colon cancer were used to evaluate whether intake of dietary, obesity, physical activity and nonsteroidal antiinflammatory drugs are associated with a CpG island methylator phenotype (CIMP). The BRAF V600E mutation and 5 CpG island markers (MINT1, MINT2, MINT31, p16 and hMLH1) were assessed in 1154 cases of colon cancer. We hypothesized that dietary factors involved in DNA methylation, cruciferous vegetables and use of aspirin/NSAIDs would be associated with CIMP-high tumors. Dietary folate, vitamins B(6) and B(12), methionine and alcohol were not associated with increased likelihood of colon tumors with the CIMP-high (2 or more markers methylated) phenotype. Dietary fiber, physical activity and aspirin and other nonsteroidal antiinflammatory drugs were inversely associated with both CIMP-low and CIMP-high tumors. Our results also suggested non-CIMP pathways as well. Obese individuals were at 2-fold increased risk of having a CIMP-low tumor. Alcohol was associated with an increased risk of tumors that were MSI+ and CIMP-low. In the presence of smoking 20 or more cigarettes per day, use of NSAIDs did not protect against a BRAF mutation. Our data suggest multiple pathways to colon cancer. They do not support a unique role for dietary folate, alcohol, vitamins B(6) and B(12) and methionine in a CpG island methylator phenotype.

A Prospective Study of Anthropometric and Clinical Measurements Associated with Insulin Resistance Syndrome and Colorectal Cancer in Male Smokers

Type 2 diabetes mellitus shares risk factors for and has shown a positive association with colorectal cancer. Anthropometric measures (height, weight, and body mass index (weight (kg)/height (m)(2)) and metabolic abnormalities associated with insulin resistance syndrome (IRS) (abnormalities in measured blood pressure, high density lipoprotein (HDL) cholesterol, and total cholesterol) were prospectively evaluated for associations with incident colon (n = 227), rectal (n = 183), and colorectal (n = 410) cancers diagnosed between 1985 and 2002 in 28,983 Finnish male smokers from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. In comparison with the lowest quintile, the highest quintile of body mass index was significantly associated with colorectal cancer (hazard ratio (HR) = 1.70, 95% confidence interval (CI): 1.01, 2.85; p-trend = 0.01), particularly colon cancer. Subjects with a cluster of three IRS-related conditions (hypertension, body mass index >/=25 kg/m(2), and HDL cholesterol level <40 mg/dl (<1.55 mmol/liter)), compared with those with fewer conditions, had a significantly increased risk of colorectal cancer (HR = 1.40, 95% CI: 1.12, 1.74), particularly colon cancer (HR = 1.58, 95% CI: 1.18, 2.10), but not rectal cancer. These results support the hypothesis that the significant association observed between IRS-defining metabolic abnormalities and colorectal cancer is determined primarily by adiposity.

Physical activity and the risk of colon cancer among women: A prospective cohort study (United States)

Physical activity has frequently been reported to decrease the risk of colon cancer in men, but data on the relation of physical activity to colon cancer risk in women have generally been less consistent. To further investigate the relationship of physical activity with colon cancer risk in women, we studied a cohort of 31,783 US women participating in the Breast Cancer Detection Demonstration Project Follow-up Study. Information on daily physical activity over the past year was ascertained using a self-administered questionnaire at study baseline. The Cox proportional hazards model was used to estimate relative risks (RRs) relating physical activity to the risk of incident colon cancer. During 270,325 person-years of follow-up, 243 colon cancer cases were identified. No association was observed between physical activity and the subsequent risk of colon cancer. The multivariable RRs of colon cancer across increasing quintiles of total physical activity were 1.0, 1.45, 1.16, 1.27 and 1.15 (95% CI: 0.76, 1.75; p(trend) = 0.77). The multivariable RRs comparing women at the extremes of moderate and vigorous physical activity, respectively, were 1.07 (95% CI: 0.70, 1.62) and 1.10 (95% CI: 0.78, 1.55). The relationship between physical activity and colon cancer risk did not vary by anatomic subsite or across subgroups defined by age, body mass, dietary fiber intake, menopausal status, menopausal hormone use or aspirin use. The results of this large prospective cohort study among women do not support the hypothesis that physical activity is related to a lower incidence of colon cancer.

Energy balance, insulin‐related genes and risk of colon and rectal cancer

Energy balance, or the ability to maintain body weight by balancing energy intake with energy expenditure, appears to be important in the etiology of colon cancer. One possible mechanism whereby energy balance may be associated with colorectal cancer is through its association with insulin. In our study, we evaluate the interaction between polymorphisms in 4 genes thought to be involved in insulin-related functions and components of energy balance with risk of colorectal cancer. Data from 2 population-based case-control studies of colon and rectal cancer conducted in Utah and Northern California were used to evaluate associations between body mass index (BMI), physical activity, energy intake and sucrose-to-fiber ratio and a CA repeat polymorphism of the IGF1 gene, the A/C polymorphism at nucleotide -202 of the IGFBP3, the G972R polymorphism of the IRS1 gene and the G1057D polymorphism of the IRS2 gene. A total of 1,346 incident colon cancer cases and 1,544 population-based controls and 952 incident rectal cancer cases and 1,205 controls were available for analysis. Inconsistent associations were identified between BMI, physical activity, energy intake and insulin-related genes. The 192/192 IGF1 genotype was associated with significant reduction in colon cancer risk among those with high physical activity (odds ratio [OR] 0.57; 95% confidence interval [CI] 0.39-0.83; p interaction 0.01). Although there was no significant pattern of interaction between either BMI or energy intake and polymorphisms assessed, specific sources of energy did appear to be more related to colon cancer risk in the presence of specific IRS2 and IGF1 genotypes. A high sucrose-to-fiber ratio increased risk of colon cancer in men who had the IRS2 DD genotype and among men who did not have the 192/192 IGF1 genotype. In summary, these data support the importance of components of energy balance in risk of colorectal cancer. Obesity, physical activity and energy intake appear to alter risk of colorectal cancer; however, the risk appears to be minimally influenced by genetic variants evaluated.

Meat Consumption and Risk of Colorectal Cancer

Consumption of red and processed meat has been associated with colorectal cancer in many but not all epidemiological studies; few studies have examined risk in relation to long-term meat intake or the association of meat with rectal cancer. To examine the relationship between recent and long-term meat consumption and the risk of incident colon and rectal cancer. A cohort of 148 610 adults aged 50 to 74 years (median, 63 years), residing in 21 states with population-based cancer registries, who provided information on meat consumption in 1982 and again in 1992/1993 when enrolled in the Cancer Prevention Study II (CPS II) Nutrition Cohort. Follow-up from time of enrollment in 1992/1993 through August 31, 2001, identified 1667 incident colorectal cancers. Participants contributed person-years at risk until death or a diagnosis of colon or rectal cancer. Incidence rate ratio (RR) of colon and rectal cancer. High intake of red and processed meat reported in 1992/1993 was associated with higher risk of colon cancer after adjusting for age and energy intake but not after further adjustment for body mass index, cigarette smoking, and other covariates. When long-term consumption was considered, persons in the highest tertile of consumption in both 1982 and 1992/1993 had higher risk of distal colon cancer associated with processed meat (RR, 1.50; 95% confidence interval [CI], 1.04-2.17), and ratio of red meat to poultry and fish (RR, 1.53; 95% CI, 1.08-2.18) relative to those persons in the lowest tertile at both time points. Long-term consumption of poultry and fish was inversely associated with risk of both proximal and distal colon cancer. High consumption of red meat reported in 1992/1993 was associated with higher risk of rectal cancer (RR, 1.71; 95% CI, 1.15-2.52; P = .007 for trend), as was high consumption reported in both 1982 and 1992/1993 (RR, 1.43; 95% CI, 1.00-2.05). Our results demonstrate the potential value of examining long-term meat consumption in assessing cancer risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.