Dietary sodium and potassium intake and colorectal cancer risk

In a large, comprehensive, population-based case-control study of colorectal cancer (The Melbourne Colorectal Cancer Study), a high intake of sodium was shown to be a statistically significant risk factor for rectal cancer in males (RR = 1.72, p = 0.01) and was close to statistical significance in females (RR = 1.58, p = 0.06). This was independent of previously described dietary risk factors and also independent of the previously described beer risk. A high intake of potassium was protective for both males and females, but this effect disappeared after adjustment was made for the previously described dietary risk factors. A high ratio of dietary potassium to sodium was a statistically significant protective factor in females for both colon and rectal cancer, and the significance of this effect was reduced after adjustment was made for the previously described dietary risk factor (RR for colon cancer = 0.70, p = 0.08; RR for rectal cancer = 0.67, p = 0.08). So far, no biological explanations are available for these associations, and while they are of obvious etiologic interest, they should be interpreted with caution.     

Body weight and physical activity as predictors of colorectal cancer risk

The associations between colorectal cancer and body weight (expressed as body mass index) and between colorectal cancer and physical activity were examined in 715 histologically confirmed cases of colorectal adenocaircinoma and 727 age‐ and sex‐matched controls. The data were obtained from a large, population‐based study, The Melbourne Colorectal Cancer Study, which was conducted in Melbourne, Australia. There was a statistically significant increase in the risk of rectal cancer but not of colon cancer in overweight and obese males but not in females. This association for males remained statistically significant after adjustment was made for dietary risk factors previously established for this study (Nutr Cancer 9, 21–42, 1987), with the exception of sodium intake, which produced a downward modification of the relative risk close to unity. The increased risk of rectal cancer in overweight and obese males was modified by beer intake, which was previously found to be a risk for rectal cancer in males in this study. Various levels of physical activity were not statistically significantly associated with the risk of colorectal cancer in either males or females. Also, the colorectal cancer risks associated with the body mass index were not significantly altered by adjustment for the physical activity level.     

Body weight and physical activity as predictors of colorectal cancer risk

The associations between colorectal cancer and body weight (expressed as body mass index) and between colorectal cancer and physical activity were examined in 715 histologically confirmed cases of colorectal adenocarcinoma and 727 age- and sex-matched controls. The data were obtained from a large, population-based study, The Melbourne Colorectal Cancer Study, which was conducted in Melbourne, Australia. There was a statistically significant increase in the risk of rectal cancer but not of colon cancer in overweight and obese males but not in females. This association for males remained statistically significant after adjustment was made for dietary risk factors previously established for this study (Nutr Cancer 9, 21-42, 1987), with the exception of sodium intake, which produced a downward modification of the relative risk close to unity. The increased risk of rectal cancer in overweight and obese males was modified by beer intake, which was previously found to be a risk for rectal cancer in males in this study. Various levels of physical activity were not statistically significantly associated with the risk of colorectal cancer in either males or females. Also, the colorectal cancer risks associated with the body mass index were not significantly altered by adjustment for the physical activity level.     

Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study

As part of a large-scale investigation of colorectal cancer (CRC) incidence, etiology, and survival, a case-control study was conducted to identify dietary factors associated with the risk of CRC. The study compared 715 cases with 727 age- and sex-matched community controls. A quantitative diet history, assessed to be the most representative of the previous 20 years, was obtained from each subject and analyzed for both food groups and nutrients. The combination of a high-fiber and high-vegetable intake was found to be protective against large bowel cancer. Cruciferous vegetable intake was also found, although with less certainty, to be protective. Dietary vitamin C was protective for estimated intakes greater than 230 mg/day. Dietary Beta-carotene had no separate association with the risk of CRC. Beef intake was a risk factor in males but not in females. Fat intake was a risk factor for both males and females. A low intake of milk drinks was a risk for both males and females. A high intake of pork and fish was protective. The use of vitamin supplements was highly protective. A risk score, which was calculated as the number of risk factors an individual has in his or her diet, showed an increasing monotonic relationship with risk of CRC. The effects of the dietary variables were similar for colon and rectal cancer and, with the exception of beef, were similar for males and females.     

Dietary intake and colon cancer: sex- and anatomic site-specific associations

A case-control study was conducted in Utah between July 1979 and June 1983 in which 231 cases of colon cancer identified through the Utah Cancer Registry and 391 controls identified through random digit dialing were interviewed. Odds ratios (OR) were calculated comparing the highest exposure categories with the lowest exposure categories. The highest quintile of body mass index (weight (kg)/height (m)2 for males; weight (kg)/height (m)1.5 for females) was associated with increased risk in both males (OR = 2.1) and females (OR = 2.3). In females, total dietary fat (OR = 1.9) and energy intake (OR = 1.5) were associated with an increased colon cancer risk after adjusting for age, body mass index, and crude fiber. Fiber was protective in females (OR = 0.5) after adjusting for age, body mass index, and energy intake, as was beta-carotene (OR = 0.5) after also adjusting for crude fiber. Adjusted risk estimates in males were 2.0 for total dietary fat, 3.8 for polyunsaturated fat, 2.1 for monounsaturated fat, 2.1 for energy intake, 2.5 for protein, 0.3 for fiber, 0.4 for beta-carotene, and 0.3 for cruciferous vegetables. Risk estimates differed by site of cancer within the colon. In males, protein (OR = 3.8) was a risk factor for cancer of the descending colon, while fats (OR = 2.7-8.8) increased the risk of cancer of the ascending colon. The hypotheses that dietary fat increases colon cancer risk while dietary fiber decreases colon cancer risk and that fat and protein may be independently associated with colon cancer risk are supported.     

Colorectal Cancer Risk and Dietary Intake of Calcium,Vitamin D,and Dairy Products: A Meta-Analysis of 26,335 Cases From 60 Observational Studies

In vivo and in vitro studies suggest that dairy products, calcium, and dietary vitamin D inhibits the development of colorectal cancer (CRC). A meta-analysis was performed to evaluate this relationship in observational studies. Data from 60 epidemiological studies enrolling 26,335 CRC cases were pooled using a general variance-based meta-analytic method. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated for the highest vs. the lowest intake categories. Sensitivity analyses tested the robustness of these summary effect measures and the statistical heterogeneity. The summary RR for high milk and dairy product intake, respectively, on colon cancer risk was 0.78 (95% CI = 0.67–0.92) and 0.84 (95% CI = 0.75–0.95). Milk intake was unrelated to rectal cancer risk. High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon. The risk reduction associated with calcium was similar for dietary and supplemental sources. Vitamin D was associated with a nonsignificant 6% reduction in CRC risk. Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC. Low vitamin D intake in the study populations may limit the ability to detect a protective effect if one exists.     

Oral contraceptive use does not protect against large bowel cancer

The association between oral contraceptive (OC) use and colorectal cancer was examined in 190 female colorectal cancer cases and 200 age-matched female controls in data derived from a population-based study of large bowel cancer, "The Melbourne Colorectal Cancer Study" conducted in Melbourne, Australia. There were 47 cases (24 colon cancer, 23 rectal cancer cases) and 39 controls, who were past OC users. After adjustment was made for the confounding factors of age, number of children and age at birth of first child, a statistically significant risk was found among rectal cancer OC users, but not among colon cancer OC users (RR rectal cancer = 2.04, 95% CI = 1.00-4.14, p = 0.04; RR colon cancer = 1.17, 95% CI = 0.59-2.29, p = 0.60). These risks were not affected by adjustment for socioeconomic level, country of birth, religion, previous diet and family history of colorectal cancer. Rectal cancer risk was higher among those OC users who were also beer drinkers (RR = 6.96, 95% CI 2.09-23.1, p = 0.001).     

Folate intake and carcinogenesis of the colon and rectum

Experimental evidence suggests that folate depletion plays a role in carcinogenesis. A case-control study examining folate intake was conducted. Some 428 colon and 372 rectal cancer cases with matched neighbourhood controls were interviewed regarding usual intake of foods, including food preparation. Unadjusted folate was not associated with risk of either cancer. Controlling for kilocalories, odds ratios (ORs) for those with the highest folate intake were 0.5 (95% confidence interval (CI): 0.24-1.03) and 0.31 (95% CI: 0.16-0.59) for females and males for rectal cancer. There was no change in colon cancer risk associated with folate intake. There was an indication of an interaction of folate and alcohol intake; the difference in risk associated with low and high folate intake was highest for males in the highest alcohol category. Associations were of similar magnitude for other dietary factors correlated with folate. It appears that intake of folate or a correlated factor may be negatively related to risk of rectal cancer.     

Colorectal cancer risk, chronic illnesses, operations and medications: case control results from the Melbourne Colorectal Cancer Study. 1988

The associations between colorectal cancer risk and several chronic illnesses, operations and various medications were examined in 715 colorectal cancer cases and 727 age- and sex-matched controls in data derived from a large, comprehensive population-based study of this cancer conducted in Melbourne, Australia. There was a statistically significant deficit among cases of hypertension, heart disease, stroke, chronic chest disease and chronic arthritis and a statistically significant excess of 'haemorrhoids' among cases, and all of these differences were consistent for both colon and rectal cancers and for both males and females. Although no statistically significant differences were found for other cancers, there were twice as many breast cancers among cases (16) than among controls (8) and also there were 9 uterine cancers among cases and only 2 among controls. There was a statistically significant deficit among cases in the use of aspirin-containing medication and vitamin supplements and this was consistent for both colon and rectal cancers and for both males and females. There was a statistically significant excess of large bowel polypectomy among cases. The modelling of these significant associations simultaneously in a logistic regression equation indicated that hypertension, heart disease, chronic arthritis and aspirin use were each independent effects and consistent for both colon and rectal cancers for both males and females and also that these effects were independent of dietary risk factors previously described in the Melbourne study. The possible relevance of these findings towards an understanding of colorectal cancer risk and aetiology is discussed.     

Cigarette smoking and risk of bladder, pancreas, kidney, and colorectal cancers in Iowa

PURPOSE: Although there are numerous reports on the effects of cigarette smoking and cancer, they have infrequently compared risks at more than one cancer site after multivariate adjustment. We analyzed data from a population-based case-control study that included five anatomic sites to evaluate the association between cigarette smoking and each cancer site and to rank the associations by site. METHODS: Study respondents included 1452 bladder, 406 kidney, 376 pancreatic, 685 colon, and 655 rectal cancer cases, as well as 2434 population controls. A self-administered questionnaire was used to collect information on cigarette smoking and other potential confounders including occupation, drinking water source, and dietary practices. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), after adjustment for age, total energy intake, and other site- and sex-specific confounders. RESULTS: In both sexes, cigarette smoking (ever vs. never) was associated with risk of bladder cancer (OR = 2.5; 95% CI, 2.0-3.1 for males; OR = 2.7; 2.0-3.6 for females) and pancreatic cancer (OR = 1.8; 1.2-2.8 for males; OR = 2.1; 1.4-3.1 for females). Cigarette smoking also increased the risk of kidney cancer among males (OR = 1.8; 1.3-2.7), and to a lesser degree, among females (OR = 1.2; 0.8-1.8). No association was found for colon or rectal cancer in either sex. CONCLUSIONS: Cigarette smoking increased the risk of bladder, kidney, and pancreatic cancer in men and women. The rankings of multivariate-adjusted ORs from highest to lowest were bladder, pancreas, kidney, and colorectum, with little difference between men and women.     

Dietary risk factors for colon and rectal cancers: a comparative case-control study

BACKGROUND: In Japan, the incidence rate of colon cancer has more rapidly increased than that of rectal cancer. The differential secular trends may be due to different dietary factors in the development of colon and rectal cancers. METHODS: To compare dietary risk factors between colon and rectal cancers, we undertook a case-control study at Aichi Cancer Center Hospital, Japan. Subjects were 507 patients with newly diagnosed colon (n = 265) and rectal (n = 242) cancers, and 2,535 cancer-free outpatients (controls). Intakes of nutrients and food groups were assessed with a food frequency questionnaire, and multivariate-adjusted odds ratios (ORs) were estimated using unconditional logistic models. RESULTS: We found a decreasing risk of colon cancer with increasing intakes of calcium and insoluble dietary fiber; the multivariate ORs across quartiles of intake were 1.00, 0.90, 0.80, and 0.67 (trend p = 0.040), and 1.00, 0.69, 0.64, and 0.65 (trend p = 0.027), respectively. For rectal cancer, a higher consumption of carotene and meat was associated with a reduced risk; the corresponding ORs were 1.00, 1.10, 0.71, and 0.70 for carotene (trend p = 0.028), and 1.00, 0.99, 0.68, and 0.72 for meat (trend p = 0.036). Carbohydrate intake was positively correlated with the risk of rectal cancer (ORs over quartiles: 1.00, 1.14, 1.42, and 1.54; trend p = 0.048). This association was stronger in women, while fat consumption was inversely correlated with the risk of female colon and rectal cancers. CONCLUSIONS: Dietary risk factors appear to considerably differ between colon and rectal cancers.     

Physical activity, diet, and risk of colon cancer in Utah

A population-based case-control study was used to assess the relations of physical activity and diet to the development of colon cancer in Utah. Data were obtained for a reference period of two years prior to interview for controls (204 females and 180 males) and two years prior to the date of diagnosis for cases (119 females and 110 males). Both leisure time and occupational activities were ascertained by level of intensity and were converted to calories expended per week for analysis. Dietary data were obtained from a quantitative food frequency questionnaire. Physical activity and dietary data were divided into quartiles based upon the distribution in the study population for analyses. Total physical activity was protective against the development of colon cancer for both males (odds ratio (OR) = 0.70) and females (OR = 0.48) when high and low quartiles of activity were compared. Intense physical activity was the component of activity that had the greatest protective effect for males (OR = 0.27); a similar relation was seen for females (OR = 0.55). The observed relation between physical activity and colon cancer was not confounded by dietary intake of calories, fat, or protein, nor was the diet and colon cancer relation confounded by physical activity (odds ratios for calories, protein, and fat in males were 2.40, 2.57, and 2.18, respectively). Assessment of the interrelations among physical activity, diet, and colon cancer suggests that physical activity modifies colon cancer risk associated with diet.     

Dietary folate and APC mutations in sporadic colorectal cancer

Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.     

饮食、营养素与结肠癌——基于全人群的病例-对照研究

本文以大样本全人群病例一对照研究数据分析食物摄入频度、摄入量及营养素与结肠癌的关系。结果表明:大多数蔬菜、粗纤维、维生素C、维生素B_2、钙、铁等营养素降低结肠癌的发病危险性;动物性食品、脂肪、能量与结肠癌的发病危险性关系不甚密切;油炸、腌制、咸霉食品增高结肠癌发病的相对危险度;葱蒜类、海带紫菜与结肠癌发病危险呈负相关。还探讨了结肠癌高低发地区病因学的异同以及膳食调查的回忆误差,食物摄入频度与摄入量对反映饮食与肿瘤之间联系的差异。     

Diet and lung cancer risk: findings from the Western New York Diet Study

This study compares the diets of 450 lung cancer cases (296 males, 154 females) with those of 902 controls (587 males, 315 females). Cases were lung cancer patients diagnosed between August 1980 and July 1984 in three western New York counties, while controls were selected from the general population of these same counties. Usual diet was estimated by detailed interviews using a modified food frequency method. Case-control comparisons were made for dietary fat, protein, fiber, calories, cholesterol, and vitamins A, C, and E according to quartiles of intake, adjusting for age and pack-years of cigarettes by multiple logistic regression. Risk was lower for males in the lowest quartile of total dietary fat intake compared with those in the highest quartile (relative risk = 0.5), although the overall trend in the association with dietary fat was not statistically significant (p = 0.12). Likewise, there was a weak, but not statistically significant, direct association between dietary cholesterol and lung cancer in men (p = 0.17). The intake of vitamin A from fruits and vegetables (carotene) was much more strongly associated with reduced cancer risk. For males, the relative risks by quartiles (lowest intake to highest intake) were 1.8, 1.8, 1.0, 1.0 (p for trend = 0.001). For females, this relation was considerably weaker, and was not statistically significant. These findings are generally in agreement with those of several previous studies. The risk reduction associated with vitamin A from fruits and vegetables (carotene) was most evident for males, for those with squamous cell cancers, for light or ex-smokers, and for those over 60 years of age.     

Calcium and vitamin D intakes in relation to risk of distal colorectal adenoma in women

The authors examined intakes of calcium and vitamin D, and interaction with retinol, in relation to risk of adenoma of the distal colon or rectum among 48,115 US women who were free of colorectal cancer or polyps, completed a food frequency questionnaire in 1980, and underwent endoscopy by 2002. They documented 2,747 cases of adenoma (1,064 large, 1,531 small, 2,085 distal colon, and 779 rectal). Total calcium intake was weakly associated with distal colorectal adenoma risk (multivariable relative risk (RR) for extreme quintiles = 0.88, 95% confidence interval (CI): 0.74, 1.04; p(trend) = 0.06), particularly for large adenoma (RR = 0.73, 95% CI: 0.56, 0.96; p(trend) = 0.02). Total vitamin D intake was weakly associated with reduced risk of distal colorectal adenoma (RR = 0.79, 95% CI: 0.63, 0.99; p(trend) = 0.07), but more strongly with distal colon adenoma risk (RR = 0.67, 95% CI: 0.52, 0.87; p(trend) = 0.004). The combinations of high vitamin D and low retinol intake (RR = 0.55, 95% CI: 0.28, 1.10) further decreased risk of distal colorectal adenoma when compared with the opposite extreme. Higher total calcium and vitamin D intakes were associated with reduced risk, and the actions of vitamin D may be attenuated by high retinol intake.     

Case-control study of alcoholic beverages as etiological factors: the Melbourne Colorectal Cancer Study

As part of a large-scale investigation of colorectal cancer incidence, etiology, and survival, a case-control study was conducted to identify whether diet and alcohol, among other variables, were associated with the risk of colorectal cancer. This study compared 715 cases with 727 age- and sex-matched community controls. Findings from the dietary data are presented in the previous paper (Nutr Cancer 9, 21-42, 1987). The total life intake of specific alcoholic beverages was obtained from each subject. Data were classified by consumption of beer, wine, spirits, and alcohol. There was little evidence of an association of any of the alcohol variables with the risk of colon cancer. However, beer was found to be a risk factor for rectal cancer. This effect was more marked in males than in females, but the relative risks for females were consistent with those for males. Relative risk estimates changed only slightly when adjusted for the other alcohol variables and for the variables in the diet model; this suggests that the beer effect is separate from that of other alcohol variables and also from dietary variables. The age differences among beer consumers were found to be associated with cancer risk. Consumption of spirits was associated with a low risk for male rectal cancer. The risk of rectal cancer appeared to depend on beer drinking patterns in the previous 15-20 years.     

叶酸、蛋氨酸摄入量,MTHFR多态性与结直肠癌关系的病例对照研究

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因多态,叶酸、蛋氨酸摄入量与结直肠癌易感性的关系。方法:应用PCR-RFLP法,检测126例结直肠癌患者和343例正常对照者的MTHFRC 677T和A1298C两个位点基因多态,比较不同基因型与结直肠癌风险的关系,以及两个多态位点与叶酸、蛋氨酸的联合作用。结果: MTHFR C677T和A1298C突变基因在对照组中的频率分别为39.7%和17.1%。MTHFR A1298C突变基因携带者与野生型相比,患结直肠癌的风险显著降低(OR=0.51,95% CI:0.27～0.95);在叶酸个别摄入量组,MTHFR C677T多态使结直肠癌的风险显著降低(OR=0.23,95% CI:0.06～0.93)。结论: MTHFR A1298C位点多态性是直肠癌的保护因素 ,在叶酸摄入充足的条件下,MTHFR C677T多态是结肠癌的保护因素。     

Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study

BACKGROUND: Whether the intake of dietary fiber can protect against colorectal cancer is a long-standing question of considerable public health import, but the epidemiologic evidence has been inconsistent. OBJECTIVE: The objective was to investigate the relation between dietary fiber and whole-grain food intakes and invasive colorectal cancer in the prospective National Institutes of Health-AARP Diet and Health Study. DESIGN: The analytic cohort consisted of 291 988 men and 197 623 women aged 50-71 y. Diet was assessed with a self-administered food-frequency questionnaire at baseline in 1995-1996; 2974 incident colorectal cancer cases were identified during 5 y of follow-up. The Cox proportional hazards model was used to estimate the relative risks (RRs) and 95% CIs. RESULTS: Total dietary fiber intake was not associated with colorectal cancer. The multivariate RR for the highest compared with the lowest intake quintile (RR(Q5-Q1)) was 0.99 (95% CI: 0.85, 1.15; P for trend = 0.96). In analyses of fiber from different food sources, only fiber from grains was associated with a lower risk of colorectal cancer (multivariate RR(Q5-Q1): 0.86; 95% CI: 0.76, 0.98; P for trend = 0.01). Whole-grain intake was inversely associated with colorectal cancer risk: the multivariate RR(Q5-Q1) was 0.79 (95% CI: 0.70, 0.89) for the whole cohort (P for trend < 0.001). The association with whole grain was stronger for rectal than for colon cancer. CONCLUSIONS: In this large prospective cohort study, total dietary fiber intake was not associated with colorectal cancer risk, whereas whole-grain consumption was associated with a modest reduced risk.     

Dietary Magnesium Intake and Risk of Cancer: A Meta-Analysis of Epidemiologic Studies

The aim of this study was to investigate the association between dietary magnesium and the risk of overall cancer using a meta-analysis. We searched PubMed, SCOPUS, and the Cochrane Review through November 2012. All the articles searched were independently reviewed by 3 authors based on predetermined selection criterion. A total of 13 epidemiologic studies, 6 case-control studies, and 7 prospective cohort studies involving 1,236,004 participants were included in the final analysis. When all studies were pooled, the relative risk (RR) of overall cancer for the highest level of dietary magnesium intake was 0.801 [95% confidence interval (CI): 0.664–0.966) compared with the lowest level of dietary magnesium intake. In subgroup meta-analyses by study design, there was a significant inverse association between dietary magnesium and the risk of cancer in case-control studies (RR = 0.663, 95% CI: 0.475–0.925), whereas there was no significant association in prospective cohort studies (RR = 0.888, 95% CI: 0.745–1.060). Furthermore, there was a significant preventive effect of dietary magnesium for colorectal cancer (RR = 0.775, 95% CI: 0.655–0.919), but not for other cancer. Our meta-analysis showed that higher dietary magnesium intake seems to have a protective effect for cancer, especially colorectal cancer and in females.