Colon cancer has been associated with several nutrients and foods. The authors used data from a population-based study conducted in Northern California, Utah, and Minnesota to examine associations between dietary eating patterns and risk of developing colon cancer. Through factor analysis, detailed dietary intake data obtained from 1,993 cases (diagnosed in 1991-1994) and 2,410 controls were grouped into factors that were evaluated for relations with lifestyle characteristics and colon cancer risk. Several dietary patterns emerged. The dietary patterns with the most variation were labeled "Western," "prudent," "high fat/sugar dairy," "substituters," and "drinkers." The "Western" dietary pattern was associated with a higher body mass index and a greater intake of total energy and dietary cholesterol. The "prudent" pattern was associated with higher levels of vigorous leisure time physical activity, smaller body size, and higher intakes of dietary fiber and folate. Persons who had high scores on the "drinker" pattern were also more likely to smoke cigarettes. The "Western" dietary pattern was associated with an increased risk of colon cancer in both men and women. The association was strongest among people diagnosed prior to age 67 years (for men, odds ratio (OR)=1.96, 95% confidence interval (CI) 1.22-3.15; for women, OR=2.02, 95% CI 1.21-3.36) and among men with distal tumors (OR=2.25, 95% CI 1.47-3.46). The "prudent" diet was protective, with the strongest associations being observed among people diagnosed prior to age 67 years (men: OR=0.63, 95% CI 0.43-0.92; women: OR=0.58, 95% CI 0.38-0.87); associations with this dietary pattern were also strong among persons with proximal tumors (men: OR=0.55, 95% CI 0.38-0.80; women: OR=0.64, 95% CI 0.45-0.92). Although "substituters" (people who substituted low fat dairy products for high fat dairy products, margarine for butter, poultry for red meat, and whole grains for refined grains) were at reduced risk of colon cancer, the reduction in risk was not statistically significant. These data support the hypothesis that overall dietary intake pattern is associated with colon cancer, and that the dietary pattern associated with the greatest increase in risk is the one which typifies a Western-style diet.

This study suggests that smoking cigarettes statistically significantly contributes to MSI in colon tumors. We estimate that approximately 21% of MSI in colon tumors may be attributable to cigarette smoking.

The major dietary sources of lutein in subjects with colon cancer and in control subjects were spinach, broccoli, lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

Purpose-The purpose of this study was to examine the prevalence rates for cervical, breast, and colorectal cancer screening among American Indian and Alaska Native people living in Alaska and in the Southwest US, and to investigate predictive factors associated with receiving each of the cancer screening tests. Methods-We used the Education and Research Towards Health (EARTH)Study to measure selfreported cancer screening prevalence rates among 11,358 study participants enrolled in [2004][2005][2006][2007]. We used prevalence odds ratios to examine demographic, lifestyle and medical factors associated with receiving age-and sex-appropriate cancer screening tests.Results-The prevalence rates of all the screening tests were higher in Alaska than in the Southwest. Pap test in the past 3 years was reported by 75.1% of women in Alaska and 64.6% of women in the Southwest. Mammography in the past 2 years was reported by 64.6% of women aged 40 years and older in Alaska and 44.0% of those in the Southwest. Colonoscopy or sigmoidoscopy in the past 5 years was reported by 41.1% of study participants aged 50 years and older in Alaska and by 11.7% of those in the Southwest US. Multivariate analysis found that location (Alaska versus the Southwest), higher educational status, income and the presence of one or more chronic medical condition predicted each of the three screening tests. Additional predictors of Pap test were age (women aged 25-39 years more likely to be screened than older or younger women), marital status (ever married more likely to be screened), and language spoken at home (speakers of American Indian Alaska Native language only less likely to be screened). Additional predictors of mammography were age (women aged 50 years and older were more likely to be screened than those aged 40-49 years), positive family history of breast cancer, use of smokeless tobacco (never users more likely to be screened), and urban/rural residency (urban residents more likely to be screened). Additional predictors of colonoscopy/sigmoidoscopy were age (men and women aged 60 years and older slightly more likely to be screened than those aged 50-59 years), family history of any cancer, family history of colorectal cancer, former smoking, language spoken at home (speakers of American Indian Alaska Native language less likely to be screened), and urban/rural residence (urban residents more likely to be screened).

The vitamin D receptor (VDR) may importantly modulate risk of colorectal cancer either independently or in conjunction with calcium and vitamin D intake. We evaluate the association between calcium, vitamin D, dairy products, and VDR polymorphisms in 2 case-control studies of colon and rectal cancer (n ‫؍‬ 2,306 cases and 2,749 controls). Dietary intake was evaluated using a detailed diet history questionnaire. Two VDR polymorphisms were evaluated: an intron 8 Bsm 1 polymorphism and a 3 untranslated region poly-A length polymorphism (designated S for short and L for long Uncontrolled cell growth is central to the carcinogenic process. Factors that regulate and control cell growth and proliferation may be important to the etiology of cancer. In the intestine, the active vitamin D metabolite, 1,25 (OH) 2 D3 is involved in regulating cell proliferation and differentiation. 1 It also has been suggested that vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation. 2 Epidemiological studies, although mixed in their assessment of the associations between calcium and vitamin D and colorectal cancer, provide support for high intakes of calcium and vitamin D being inversely related to colorectal cancer. [3][4][5][6][7][8] The protective effects of calcium have been strengthened by observations from clinical trials showing significant reduction in adenoma recurrence with calcium supplementation. 9,10 These studies further suggest that these associations may be stronger for distal rather than proximal colon tumors and may vary by age at diagnosis. 7,11,12 The vitamin D receptor (VDR), a nuclear hormone receptor, is essential for vitamin D action and calcium homeostasis. Several polymorphisms of the VDR gene have been identified, including 2 restriction fragment length polymorphisms (RFLPs) in intron 8 (Bsm I and Apa I) and one in exon 9 (Taq I). These are in linkage disequilibrium with each other and with several 3Ј untranslated region (3Ј UTR) polymorphisms, including a poly A repeat. 13,14 The presence of the B, A, and t RFLP alleles (capital letters denote absence of restriction site; small letters presence of restriction site for Bsm I, Apa I, and Taq I RFLPs, respectively) and the relatively short poly-A alleles are highly correlated. These alleles, either alone or in combination, have been associated with increased mRNA expression of the VDR gene, increased serum levels of 1,25-dihydroxy vitamin D, and increased levels of osteocalcin. [15][16][17] The RFLP polymorphisms are most likely not of functional consequence, and the reported associations are probably due to linkage disequilibrium with some 3ЈUTR element, which may or may not be the poly-A repeat. 18 The B and short poly-A alleles have been reported to be protective against the development of colonic adenomas and prostate cancer, respectively. 18 -21 At the start site of the gene, a polymorphism detected with a Fok I digest also has been studied and has been shown to not be in linkage disequilibrium wit...

Some studies have reported that p53 mutations or certain types of p53 mutation are associated with poor prognosis in colon cancer, while other studies have failed to show such a relationship. None of these previous studies was populationbased. We therefore evaluated the prognostic significance of p53 mutations in a large, population-based study of 1,464 individuals with colon cancer from Utah and California. Mutations in exons 5-8 were detected by SSCP analysis, followed by sequencing of aberrant bands. p53 mutations were identified in colon cancers from 665 of 1,464 (45.4%) individuals. p53 mutations were significantly more common in distal tumors (p < 0.01), tumors of relatively high stage (p ‫؍‬ 0.04), tumors without MSI (p < 0.01) and tumors without Ki-ras mutations (p < 0.01). In a univariate analysis, tumors with p53 mutations were associated with a significantly worse 5-year survival than those with wild-type p53 (53.4% vs. 58.8%, p ‫؍‬ 0.04); significantly worse prognosis also was seen with missense mutations, transitions, transversions, mutations affecting the structure of the p53 molecule, mutations within the ␤-sandwich motif and mutations in proximal tumors. In multivariate analyses, however, the only significant predictors of poor prognosis were G245 hot spot mutations (HRR ‫؍‬ 2.16, 95% CI 1.06 -4.40) and p53 mutations in proximal tumors (HRR ‫؍‬ 1.34, 95% CI 1.07-1.63). We conclude that overall p53 mutational status is not an independent predictor of poor prognosis in colon cancer. However, specific classes of mutations, namely, the G245 hot spot mutation and mutations in proximal tumors, are related to significantly worse survival even after adjusting for age and stage. © 2002 Wiley-Liss, Inc.Key words: p53; colon cancer; prognosis; microsatellite instability; Ki-ras p53 is a very commonly mutated gene in colon cancer. Some previous studies have reported that the presence of p53 mutations in colon cancer indicates a relatively poor prognosis, 1-16 while other studies have failed to show such a relationship. 17-27 Some of these studies directly evaluated p53 mutational status, 1-9,17-22 while many others used p53 overexpression by immunoperoxidase staining as an indirect measure of p53 mutations. 10 -16,23-27 Important structural motifs in the core domain of p53, that portion of the molecule responsible for DNA binding and the site of most mutations, have been identified. These motifs include a ␤-sandwich scaffold, 2 large loops (L2 and L3) that contain a zinc binding domain and an LSH, with the actual DNA binding surface being formed by parts of the 2 loops and the LSH. 28 Most p53 mutations are missense in nature, and it is possible that missense mutations affecting different structural motifs could have different effects on p53 function and, therefore, different prognostic significance. It also is possible to classify mutations in other ways, e.g., those that directly contact DNA vs. those that affect the overall structure of the p53 molecule or missense mutations vs. inactivating mutations. ...

Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERa and ERb) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A>G XbaI polymorphism of ERa, the 1,082 G>A and CA repeat polymorphisms of ERb, and the CAG repeat of AR. Having two 25 or more CA repeats in ERb was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13; 95% confidence interval (95% CI), 1.24-3.64] but not in men (P interaction relative excess risk from interaction < 0.01; multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28; 95% CI, 1.06-1.54), but not women (OR, 0.83; 95% CI, 0.68-1.02); the interaction P value for AR gene  sex was <0.01. Taking hormone replacement therapy (HRT) was associated with a reduced risk of colon cancer in the presence of the R allele of the ERb gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had z25 CA repeats of the ERb gene had over a 6-fold increased risk of colon cancer (OR, 6.71; 95% CI, 2.89-15.6). Our results suggest that the ERb gene is more important than ERA in the etiology of colorectal cancer. (Cancer Epidemiol Biomarkers Prev 2005;14(12):2936 -42)

Ferric citrate (FC) is a phosphate binder with shown efficacy and additional effects on iron stores and use of intravenous (iv) iron and erythropoiesis-stimulating agents (ESAs). We provide detailed analyses of changes in iron/hematologic parameters and iv iron/ESA use at time points throughout the active control period of a phase 3 international randomized clinical trial. In all, 441 subjects were randomized (292 to FC and 149 to sevelamer carbonate and/or calcium acetate [active control (AC)]) and followed for 52 weeks. Subjects on FC had increased ferritin and transferrin saturation (TSAT) levels compared with subjects on AC by week 12 (change in ferritin, 114.1629.35 ng/ml; P,0.001; change in TSAT, 8.62%61.57%; P,0.001). Change in TSAT plateaued at this point, whereas change in ferritin increased through week 24, remaining relatively stable thereafter. Subjects on FC needed less iv iron compared with subjects on AC over 52 weeks (median [interquartile range] dose=12.9 [1.0-28.9] versus 26.8 [13.4-47.6] mg/wk; P,0.001), and the percentage of subjects not requiring iv iron was higher with FC (P,0.001). Cumulative ESA over 52 weeks was lower with FC than AC (median [interquartile range] dose=5303 [2023-9695] versus 6954 [2664-12,375] units/wk; P=0.04). Overall, 90.3% of subjects on FC and 89.3% of subjects on AC experienced adverse events. In conclusion, treatment with FC as a phosphate binder results in increased iron parameters apparent after 12 weeks and reduces iv iron and ESA use while maintaining hemoglobin over 52 weeks, with a safety profile similar to that of available binders.