Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: a prospective study

To examine the relation between serum fatty acids and risk of colorectal cancer, the authors conducted a nested case-control study of 169 colorectal cancer cases and 481 controls matched by age and enrollment area as part of the Japan Collaborative Cohort Study. Serum samples were donated by subjects at baseline (between 1988 and 1990) and were stored at -80 degrees C until 2002. Serum fatty acid levels were measured by using gas chromatography and were expressed as the weight percentage of total lipids. Conditional logistic regression analyses adjusted for lifestyle factors revealed that total omega-3 polyunsaturated fatty acids (odds ratio = 0.24, 95% confidence interval: 0.08, 0.76), alpha-linolenic acid (odds ratio = 0.39, 95% confidence interval: 0.16, 0.91), docosapentaenoic acid (odds ratio = 0.30, 95% confidence interval: 0.11, 0.80), and docosahexaenoic acid (odds ratio = 0.23, 95% confidence interval: 0.07, 0.76) all showed a significantly decreased risk for the highest versus the lowest quartile levels for colorectal cancer in men. For women, a weak negative association was observed between docosapentaenoic acid and colorectal cancer risk, although it was not statistically significant. No adverse effects of high serum levels of omega-6 polyunsaturated fatty acids on colorectal cancer risk were detected.     

Dietary fat and fatty acids and risk of colorectal cancer in women

The authors examined the association of intakes of different types of fat and fatty acids with risk of colorectal cancer using data from the Women's Health Study, a randomized trial of low-dose aspirin and vitamin E carried out among 39,876 healthy US women aged >/=45 years. Among the 37,547 women eligible for the present study, 202 developed colorectal cancer during an average follow-up period of 8.7 years (1993-2003). Intakes of dietary fat and its food sources were assessed at baseline by food frequency questionnaire. Cox proportional hazards regression was used to estimate relative risks and 95% confidence intervals. Total fat intake was not related to colorectal cancer risk, nor were intakes of the different types of fat and major fatty acids. However, the authors observed a positive association between intake of fried foods away from home and colorectal cancer risk (highest quintile vs. lowest: relative risk = 1.86, 95% confidence interval: 1.09, 3.16; p for trend = 0.01). These prospective cohort data provide little support for an association between dietary fat and colorectal cancer risk. However, intake of fried foods and/or other factors related to their intake may be associated with colorectal cancer development. This finding warrants further examination.     

Magnesium intake and reduced risk of colon cancer in a prospective study of women

A recent prospective study among Swedish women suggested an inverse association of dietary magnesium intake with incidence of colorectal cancer. The authors assessed this association in a cohort of 35,196 Iowa women initially free of cancer and aged 55-69 years in 1986. Intakes of magnesium and other nutrients were assessed by food frequency questionnaire at baseline. Over 17 years of follow-up through 2002, 1,112 women developed colorectal cancer. After adjustment for age, energy, other nutrients, and risk factors for colorectal cancer, the hazard ratios of colorectal cancer across quintiles of magnesium intake were 1.00, 0.96, 0.83, 0.87, and 0.80 (95% confidence interval: 0.62, 1.03; p(trend) = 0.06). The association was largely absent for rectal cancer but, for colon cancer, the hazard ratios were 1.00, 1.00, 0.88, 0.85, and 0.77 (95% confidence interval: 0.58, 1.03; p(trend) = 0.04). These findings offer further evidence that a diet high in magnesium may reduce the occurrence of colon cancer among women. If replicated by other observational studies, a clinical trial would be needed to determine whether it is magnesium, specifically, and not other aspects of the contributing foods, that may offer benefit.     

Physical activity and reduced risk of incident sporadic colorectal adenomas: observational support for mechanisms involving energy balance and inflammation modulation

To investigate the role of physical activity, energy balance, and inflammation on the risk of incident sporadic colorectal adenoma, the authors conducted a community- and colonoscopy-based case-control study (n = 177 cases, n = 228 controls) in Winston-Salem and Charlotte, North Carolina, from 1995 to 1997. Participants reported energy intake by a semiquantitative food frequency questionnaire, daily physical activity levels by a standardized questionnaire, and anthropometrics by self-assessment. The odds ratios for adenomas comparing the highest and lowest quantiles of exposure were 0.63 (95% confidence interval (CI): 0.34, 1.17) for physical activity, 0.80 (95% CI: 0.37, 1.73) for total energy intake, 0.70 (95% CI: 0.37, 1.34) for body mass index, 1.46 (95% CI: 0.73, 2.92) for waist/hip ratio, and 2.40 (95% CI: 1.24, 4.63) for height. For the combined effects of these factors, risk was particularly low for those with higher physical activity and low waist/hip ratio (odds ratio = 0.37, 95% CI: 0.18, 0.75) or shorter stature (odds ratio = 0.32, 95% CI: 0.16, 0.62). The inverse effect of physical activity was apparent only among those not taking nonsteroidal antiinflammatory drugs (odds ratio = 0.49, 95% CI: 0.25, 0.94). These findings add further evidence that physical activity and overall patterns indicating positive energy balance increase the risk of adenoma. Furthermore, the results suggest indirectly that biologic mechanisms related to inflammation may play a role in the beneficial effect of physical activity on the risk of incident adenoma.     

Joint effects of family history and adult life dietary risk factors on colorectal cancer risk

BACKGROUND: We analyzed the joint effects of family history of colorectal cancer and adult life dietary risk factors on colorectal cancer risk. METHODS: We used data from a case-control study conducted in northern Italy between 1985 and 1992, including 1584 cases with colorectal cancer and 2879 controls. We created an adult life dietary risk factor score. RESULTS: Among subjects with family history of colorectal cancer, those in the lowest risk score tertile were not at elevated risk of colorectal cancer (odds ratio = 1.2; 95% confidence interval = 0.7-2.1), whereas those in the highest score tertile were at increased risk (odds ratio = 5.5; 95% confidence interval = 3.5-8.7). CONCLUSIONS: These findings indicate that the expression of familial susceptibility can be substantially modified by adult life risk factors.     

Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies

Animal studies show favorable effects of n-3 fatty acids on inflammation and cancer, but results from epidemiologic studies appear to be inconsistent. The authors conducted meta-analyses of prospective cohort studies that evaluated the association between fish consumption or n-3 fatty acids and colorectal cancer incidence or mortality. Random-effects models were used, and heterogeneity between study results was explored through stratified analyses. The pooled relative risks for the highest compared with the lowest fish consumption category were 0.88 (95% confidence interval: 0.78, 1.00) for colorectal cancer incidence (14 studies) and 1.02 (95% confidence interval: 0.90, 1.16) for colorectal cancer mortality (four studies). The pooled relative risks for colorectal cancer incidence were 0.96 (95% confidence interval: 0.92, 1.00) for each extra occurrence of fish consumption per week (seven studies) and 0.97 (95% confidence interval: 0.92, 1.03) for each extra 100 g of fish consumed per week (four studies). Stratified analysis showed that the pooled relative risk for colorectal cancer incidence was more pronounced for women and in studies with a large exposure contrast. In cohort studies, fish consumption was shown to slightly reduce colorectal cancer risk. Existing evidence that n-3 fatty acids inhibit colorectal carcinogenesis is in line with these results, but few data are available addressing this association.     

Oral contraceptives, reproductive factors, and risk of colorectal cancer among women in a prospective cohort study

Previous findings on the associations between oral contraceptive (OC) use and reproductive factors and risk of colorectal cancer have been inconclusive. The authors evaluated associations of OC use and reproductive factors (including parity, age at first birth, age at menarche, and age at menopause) with risk of colorectal cancer among women in a large-scale prospective cohort study. The analysis included 39,680 participants in the Women's Health Study who had usable information on ever use of OCs and potential risk factors for colorectal cancer. Relative risks and 95% confidence intervals were estimated from Cox proportional hazards regression models. All p values were two-sided. During an average of 11 years of follow-up (1992-2004), 267 incident cases of colorectal cancer were documented. Ever use of OCs was associated with a lower risk of colorectal cancer (relative risk = 0.67, 95% confidence interval: 0.50, 0.89). Women who had used OCs for 6 months-<3 years had a relative risk of 0.61 (95% confidence interval: 0.40, 0.94) relative to never users, with little additional decreased risk being seen with longer duration of use (p for multivariate trend = 0.09). No significant association was observed between reproductive factors and colorectal cancer risk. These findings provide some support for a potential role of OCs in reducing risk of colorectal cancer.     

Fat intake and risk of squamous cell carcinoma of the skin

The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin.     

Serum phospholipid fatty acids and prostate cancer risk: results from the prostate cancer prevention trial

Inflammation may be involved in prostate cancer development and progression. This study examined the associations between inflammation-related phospholipid fatty acids and the 7-year-period prevalence of prostate cancer in a nested case-control analysis of participants, aged 55-84 years, in the Prostate Cancer Prevention Trial during 1994-2003. Cases (n = 1,658) were frequency matched to controls (n = 1,803) on age, treatment, and prostate cancer family history. Phospholipid fatty acids were extracted from serum, and concentrations of ω-3, ω-6, and trans-fatty acids (TFAs) were expressed as proportions of the total. Logistic regression models estimated odds ratios and 95% confidence intervals of associations of fatty acids with prostate cancer by grade. No fatty acids were associated with low-grade prostate cancer risk. Docosahexaenoic acid was positively associated with high-grade disease (quartile 4 vs. 1: odds ratio (OR) = 2.50, 95% confidence interval (CI): 1.34, 4.65); TFA 18:1 and TFA 18:2 were linearly and inversely associated with risk of high-grade prostate cancer (quartile 4 vs. 1: TFA 18:1, OR = 0.55, 95% CI: 0.30, 0.98; TFA 18:2, OR = 0.48, 95% CI: 0.27, 0.84). The study findings are contrary to those expected from the pro- and antiinflammatory effects of these fatty acids and suggest a greater complexity of effects of these nutrients with regard to prostate cancer risk.     

Dietary patterns and colorectal adenomas in Japanese men: the Self-Defense Forces Health Study

The role of dietary patterns in colorectal carcinogenesis remains unclear in Asian populations. Using 1999-2002 data, the authors investigated the association between dietary patterns and colorectal adenomas in 1,341 Japanese men who underwent total colonoscopy. Information about diet was obtained using a 74-item food frequency questionnaire prior to the colonoscopy. Three dietary patterns were generated by factor analysis: 1) a high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; 2) an "animal food" pattern; and 3) a Japanese pattern. Logistic regression analysis was used to estimate the odds ratio of having colorectal adenomas with the adjustment for potential confounding variables including body mass index, smoking, alcohol, and leisure-time physical activities. A significant inverse association was found for the high-dairy, high-fruit and -vegetable, high-starch, low-alcohol pattern; the odds ratios for the second, third, and fourth quartiles were 0.97 (95% confidence interval: 0.70, 1.36), 0.71 (95% confidence interval: 0.50, 1.01), and 0.62 (95% confidence interval: 0.43, 0.90), respectively, compared with the lowest (p(trend) = 0.003). Similar associations were observed for larger adenomas or for each subsite of the colorectum. The Japanese and "animal food" patterns were not clearly associated with colorectal adenomas. A dietary pattern including greater consumption of dairy products and fruits and vegetables with low alcohol consumption may be associated with decreased risk of colorectal adenomas.     

Alcohol consumption and metabolic syndrome: does the type of beverage matter?

OBJECTIVE: To examine the association between total and beverage-specific alcohol consumption and the prevalence odds of metabolic syndrome (MS). RESEARCH METHODS AND PROCEDURES: Using a cross-sectional design, we studied 4510 white participants of the National Heart, Lung, and Blood Institute Family Heart Study. We used generalized estimating equations adjusting for age, education, risk group, smoking, physical activity, diabetes mellitus, coronary heart disease, energy intake, energy from fat, fruits, and vegetables, dietary cholesterol, dietary fiber, and use of multivitamins to estimate the prevalence odds of MS by alcohol intake. RESULTS: Compared with never-drinkers, multivariate odds ratios (95% confidence interval) for MS were 1.12 (0.85 to 1.49), 0.68 (0.36 to 1.28), 0.72 (0.50 to 1.03), 0.66 (0.44 to 0.99), and 0.80 (0.55 to 1.16) among men who were former drinkers and who were current drinkers of 0.1 to 2.5, 2.6 to 12.0, 12.1 to 24.0, and >24.0 g/d of alcohol, respectively (p for linear trend 0.018). Corresponding values for women were 0.86 (0.69 to 1.09), 0.80 (0.43 to 1.34), 0.47 (0.33 to 0.66), 0.47 (0.30 to 0.74), and 0.39 (0.21 to 0.74), respectively (p for trend < 0.0001). The reduced prevalence odds of MS was observed across all beverage types: compared with never-drinkers, multivariate adjusted odds ratios (95% confidence interval) of MS were 0.32 (0.14 to 0.73), 0.42 (0.23 to 0.77), 0.57 (0.30 to 1.09), and 0.56 (0.36 to 0.88) for subjects who consumed >7 drinks/wk of wine only, beer only, spirits only, and more than one type of beverage, respectively. DISCUSSION: Our data indicate that alcohol consumption is associated with a lower prevalence of MS irrespective of the type of beverage consumed. Prospective studies are needed to confirm these findings and to assess the influence of drinking patterns on the alcohol-MS association.     

Causal knowledge as a prerequisite for confounding evaluation: an application to birth defects epidemiology.

Common strategies to decide whether a variable is a confounder that should be adjusted for in the analysis rely mostly on statistical criteria. The authors present findings from the Slone Epidemiology Unit Birth Defects Study, 1992-1997, a case-control study on folic acid supplementation and risk of neural tube defects. When statistical strategies for confounding evaluation are used, the adjusted odds ratio is 0.80 (95% confidence interval: 0.62, 1.21). However, the consideration of a priori causal knowledge suggests that the crude odds ratio of 0.65 (95% confidence interval: 0.46, 0.94) should be used because the adjusted odds ratio is invalid. Causal diagrams are used to encode qualitative a priori subject matter knowledge.     

Roles of religious involvement and social support in the risk of colon cancer among Blacks and Whites

This population-based case-control study of Blacks and Whites in North Carolina (1996-2000) examined the relation between social ties, etiology of colon cancer, and stage of disease at diagnosis. Interviews were conducted with 637 cases and 1,043 controls. Information was collected on two dimensions of social ties, structural (network) dimensions and functional (emotional and tangible help) dimensions. Infrequent attendance at religious services (less than once per month) was associated with a regional/advanced stage of colon cancer at diagnosis in Whites (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.09, 2.57; p for trend = 0.02) but not in Blacks (OR = 1.21, 95% CI: 0.66, 2.21; p for trend = 0.80). Among Blacks, minimal emotional support was strongly associated with risk of colon cancer (OR = 4.62, 95% CI: 2.06, 10.35; p for trend < 0.001) and with both local (OR = 3.69, 95% CI: 1.08, 12.69; p for trend < 0.001) and advanced (OR = 5.10, 95% CI: 2.03, 12.82; p for trend < 0.01) disease. No associations between emotional support and risk of colon cancer or stage of disease were observed among Whites. These results suggest that certain characteristics of social ties are associated with both risk of and prognostic indicators for colon cancer.     

Dietary (n-3)/(n-6) fatty acid ratio: possible relationship to premenopausal but not postmenopausal breast cancer risk in U.S. women

Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.     

Long-term sedentary work and the risk of subsite-specific colorectal cancer

Research suggests that sedentary behavior may increase the risk of some chronic diseases. The aims of the study were to examine whether sedentary work is associated with colorectal cancer and to determine whether the association differs by subsite. A total of 918 cases and 1,021 controls participated in a population-based case-control study of colorectal cancer in Western Australia in 2005-2007. Data were collected on lifestyle, physical activity, and lifetime job history. The estimated effects of sedentary work on the risk of cancers of the proximal colon, distal colon, and rectum were analyzed by using multinomial logistic regression. Compared with participants who did not spend any time in sedentary work, participants who spent 10 or more years in sedentary work had almost twice the risk of distal colon cancer (adjusted odds ratio = 1.94, 95% confidence interval: 1.28, 2.93) and a 44% increased risk of rectal cancer (adjusted odds ratio = 1.44, 95% confidence interval: 0.96, 2.18). This association was independent of recreational physical activity and was seen even among the most recreationally active participants. Sedentary work was not associated with the risk of proximal colon cancer. These results suggest that long-term sedentary work may increase the risk of distal colon cancer and rectal cancer.     

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.     

Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study

The relation between body size and breast cancer risk was investigated in a population-based, case-control study of Black women (350 cases, 353 controls) and White women (523 cases, 471 controls) from North Carolina, aged 20-74 years in 1993-1996. Logistic regression analyses compared tertiles of each body size variable, adjusting for age and breast cancer risk factors (results shown for highest relative to lowest tertile). Among premenopausal women, body mass index (kg/m2) was inversely associated with breast cancer (odds ratio (OR) = 0.46, 95% confidence interval (CI): 0.26, 0.80) for Whites but not for Blacks. There was essentially no association among postmenopausal women. Higher waist/hip ratio, adjusted for body mass index, increased risk for all women. Odds ratios for Black and White premenopausal women were 2.50 (95% CI: 1.10, 5.67) and 2.44 (95% CI: 1.17, 5.09), respectively; odds ratios for Black and White postmenopausal women were 1.62 (95% CI: 0.70, 3.79) and 1.64 (95% CI: 0.88, 3.07), respectively. Findings for body mass index differed among Black women when stratified by age (<50 years) (OR = 0.50, 95% CI: 0.25, 1.01) instead of menopausal status. Thus, the associations of breast cancer with body mass index and waist/hip ratio among Black women are similar to those documented for Whites, despite different body size profiles on average.     

Plasma enterolignan concentrations and colorectal cancer risk in a nested case-control study

Enterolignans are biphenolic compounds that possess several biologic activities whereby they may influence carcinogenesis. The authors investigated the association between plasma enterolactone and enterodiol and colorectal cancer risk in a Dutch prospective study. Among more than 35,000 participants aged 20-59 years, 160 colorectal cancer cases were diagnosed after 7.5 years of follow-up (1987-2003). Cohort members who were frequency-matched to the cases on age, sex, and study center were selected as controls (n = 387). Plasma enterodiol and enterolactone were not associated with risk of colorectal cancer after adjustment for known colorectal cancer risk factors (highest quartile vs. lowest: for enterodiol, odds ratio = 1.11, 95% confidence interval: 0.56, 2.20 (p-trend = 0.75); for enterolactone, odds ratio = 1.70, 95% confidence interval: 0.88, 3.27 (p-trend = 0.15)). However, sex (p-interaction = 0.06) and body mass index (p-interaction < 0.01) modified the relation between plasma enterolactone and colorectal cancer risk; increased risks were observed among women and subjects with a high body mass index. The association between plasma enterodiol and colorectal cancer risk was modified by smoking status; risk was increased among current smokers (p-interaction < 0.01). These findings do not support the hypothesis that high plasma enterodiol or enterolactone concentrations are associated with reduced risk of colorectal cancer.     

Physical activity and mortality: is the association explained by genetic selection?

Public health recommendations promote physical activity to improve health and longevity. Recent data suggest that the association between physical activity and mortality may be due to genetic selection. Using data on twins, the authors investigated whether genetic selection explains the association between physical activity and mortality. Data were based on a postal questionnaire answered by 13,109 Swedish twin pairs in 1972. The national Cause of Death Register was used for information about all-cause mortality (n=1,800) and cardiovascular disease mortality (n=638) during 1975-2004. The risk of death was reduced by 34% for men (relative risk=0.64, 95% confidence interval: 0.50, 0.83) and by 25% for women (relative risk=0.75, 95% confidence interval: 0.50, 1.14) reporting high physical activity levels. Within-pair comparisons of monozygotic twins showed that, compared with their less active co-twin, the more active twin had a 20% (odds ratio=0.80, 95% confidence interval: 0.65, 0.99) reduced risk of all-cause mortality and a 32% (odds ratio=0.68, 95% confidence interval: 0.49, 0.95) reduced risk of cardiovascular disease mortality. Results indicate that physical activity is associated with a reduced risk of mortality not due to genetic selection. This finding supports a causal link between physical activity and mortality.