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Mai Yamauchi,
Paul Lochhead,
Yu Imamura,
Aya Kuchiba,
Xiaoyun Liao,
Zhi Rong Qian,
Reiko Nishihara,
Teppei Morikawa,
Kaori Shima, Kana Wu,
Edward Giovannucci,
Jeffrey A Meyerhardt,
Charles S Fuchs,
Andrew T Chan,
Shuji Ogino
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ABSTRACT: BACKGROUND: Higher levels of physical activity are associated with lower colorectal cancer incidence and mortality, perhaps through influencing energy balance, cellular prostaglandin biosynthesis and systemic inflammation. Although evidence suggests interactive effects of energetics, sedentary lifestyle, and tumor CTNNB1 (beta-catenin) or CDKN1B (p27) status on colon cancer prognosis, interactive effects of physical activity and tumor PTGS2 (the official symbol for cyclooxygenase-2) status on clinical outcome remain unknown. METHODS: Utilizing molecular pathological epidemiology database of 605 stage I-III colon and rectal cancers in two prospective cohort studies (the Nurse's Health Study and the Health Professionals Follow-up Study), we examined patient survival according to post-diagnosis physical activity and tumor PTGS2 status (with 382 PTGS2-positive and 223 PTGS2-negative tumors by immunohistochemistry). Cox proportional hazards models were used to calculate colorectal cancer-specific mortality hazard ratio (HR), adjusting for clinical and other tumor variables including microsatellite instability status. RESULTS: Among PTGS2-positive cases, compared with the least active first quartile, the multivariate HRs (95% confidence interval) were 0.30 (0.14-0.62) for the second, 0.38 (0.20-0.71) for the third, and 0.18 (0.08-0.41) for the fourth quartile of physical activity level (Ptrend=0.0002). In contrast, among PTGS2-negative cases, physical activity level was not significantly associated with survival (Ptrend =0.84; Pinteraction=0.024, between physical activity and tumor PTGS2 status). CONCLUSIONS: Post-diagnosis physical activity is associated with better survival among patients with PTGS2-positive tumors, but not among patients with PTGS2-negative tumors. Impact: Immunohistochemical PTGS2 expression in colorectal carcinoma may serve as a predictive biomarker in pathology practice, which may predict stronger benefit from exercise.
Cancer Epidemiology Biomarkers & Prevention 04/2013; · 4.12 Impact Factor
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ABSTRACT: PURPOSE: The associations between bowel movement frequency, laxative use, and colorectal cancer incidence remain uncertain. No published studies have accounted for potential latency between these factors and colorectal cancer onset. METHODS: We prospectively examined these associations among 88,173 women in the Nurses' Health Study (NHS, 1982-2010) and 23,722 men in the Health Professionals Follow-up Study (HPFS, 2000-2010). Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95 % CIs). We conducted time lagged analyses to evaluate the potential latency in the NHS. RESULTS: We documented 2,012 incident colorectal cancer cases. The HRs (95 % CIs) for infrequent bowel movement relative to daily were 0.86 (95 % CI 0.71-1.04) in women and 0.81 (95 % CI 0.48-1.37) in men. The HRs for weekly to daily relative to never laxative use were 0.98 (95 % CI 0.81-1.20) in women and 1.41 (95 % CI 0.96-2.06) in men. In women, the HRs for every 3 days or less bowel movement relative to daily were 0.87 (95 % CI 0.59-1.27) for colorectal cancers that developed within 10 years of assessment, 1.03 (95 % CI 0.85-1.26) for 11-18 years after assessment, and 0.73 (95 % CI 0.54-1.01) for 19-28 years after assessment. The corresponding HRs for weekly to daily relative to never laxative use were 0.93 (95 % CI 0.63-1.37), 1.03 (95 % CI 0.74-1.44), and 0.98 (95 % CI 0.71-1.35), respectively. CONCLUSION: Bowel movement frequency and laxative use appear not to be associated with colorectal cancer risk in this study.
Cancer Causes and Control 03/2013; · 2.88 Impact Factor
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ABSTRACT: PURPOSE: Carotenoids have been hypothesized to prevent carcinogenesis through their antioxidant and pro-vitamin A properties. We examined associations between intakes of specific carotenoids and risk of colorectal adenomas. METHODS: Among 29,363 men who reported having a lower bowel endoscopy between 1986 and 2006, 3,997 cases of colorectal adenoma were identified in the Health Professionals Follow-up Study. Participants completed food frequency questionnaires every 4 years; dietary information was cumulatively updated. The associations between carotenoid intakes and risk of colorectal adenomas overall and by anatomic site, stage, smoking status and alcohol consumption were investigated using multivariate logistic regression models. RESULTS: Total β-carotene and dietary β-carotene, lycopene and lutein/zeaxanthin intakes and the total carotenoid score were inversely associated with colorectal adenoma risk. The odds ratios (95 % confidence intervals) comparing the highest versus lowest quintile of intake were 0.78 (0.69-0.88) for total β-carotene, 0.72 (0.64-0.81) for dietary β-carotene, 0.83 (0.74-0.93) for lycopene, 0.86 (0.76-0.96) for lutein/zeaxanthin, and 0.87 (0.77-0.97) for the total carotenoid score. Associations for α-carotene and β-cryptoxanthin intakes were null. We did not find significant differences in the associations between intakes of each carotenoid and risk of colorectal adenoma by anatomic site or stage (all p values, test for common effects >0.10). The inverse associations we observed for total β-carotene and dietary β-carotene, lycopene, and lutein/zeaxanthin intakes and the total carotenoid score with adenoma risk also did not vary by smoking status and alcohol consumption. CONCLUSION: This study found that a diet high in carotenoids was associated with a reduced risk of colorectal adenomas.
Cancer Causes and Control 02/2013; · 2.88 Impact Factor
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ABSTRACT: Abnormal one-carbon metabolism may lead to general genomic (global) hypomethylation, which may predispose an individual to the development of colorectal neoplasia.
We evaluated the association between pre-diagnostic leukocyte genomic DNA methylation level and the risk of colorectal cancer in a nested case-control study of 358 colorectal cancer cases and 661 matched controls within the all-female cohort of the Nurses' Health Study (NHS). Among control subjects, we further examined major plasma components in the one-carbon metabolism pathway in relation to genomic DNA methylation level. Liquid chromatography/tandem mass spectrometry was used to examine leukocyte genomic DNA methylation level. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression.
Overall genomic DNA methylation level was not associated with the risk of colorectal cancer (p for trend, 0.45). Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer risk was 1.32 (95% CI, 0.82-2.13) for those in the highest quintile. We did not find significant associations between major plasma components of one-carbon metabolism or risk factors for colorectal cancer and genomic DNA methylation level (all p for trend >0.05). Also, neither one-carbon metabolism-related plasma components nor well-known risk factors for colorectal cancer modified the association between genomic DNA methylation level and the risk of colorectal cancer (all p for interaction >0.05).
We found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed to investigate the association between pre-diagnostic genomic DNA methylation level and colorectal cancer risk among diverse populations.
PLoS ONE 01/2013; 8(4):e59455. · 4.09 Impact Factor
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Xuehong Zhang,
Edward L Giovannucci, Kana Wu,
Xiang Gao,
Frank Hu,
Shuji Ogino,
Eva S Schernhammer,
Charles S Fuchs,
Susan Redline,
Walter C Willett,
Jing Ma
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ABSTRACT: We assessed the relationship between sleep duration, snoring and colorectal cancer risk.
Prospective cohort studies.
United States.
A total of 30,121 men aged 41 to 79 years in the Health Professionals Follow-up Study and 76,368 women aged 40 to 73 years in the Nurses' Health Study.
None.
We queried information on sleep duration and snoring in 1986/87. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs, 95% CIs). We documented 1,973 incident colorectal cancer cases (709 men and 1,264 women) over a 22-year follow-up period. Compared to sleep an average 7 h, ≥ 9 h of sleep was significantly associated with a higher risk of colorectal cancer among men (HR = 1.35, 95% CI: 1.00, 1.82), and to a lesser degree, among women (HR = 1.11, 95% CI: 0.85, 1.44). The risk associated with longer sleep was restricted to individuals who regularly snored (men: HR = 1.80, 95% CI: 1.14, 2.84; women: HR = 2.32, 95% CI: 1.24, 4.36) and to overweight individuals (i.e., BMI ≥ 25 kg/m(2)) (men: HR = 1.52, 95% CI: 1.04, 2.21; women: HR = 1.37, 95% CI: 0.97, 1.94). Short sleep duration (≤ 5 h) was not associated with an increased risk of colorectal cancer in the entire sample or in subgroups stratified by snoring or BMI.
Longer sleep duration was associated with an increased risk of developing colorectal cancer among individuals who were overweight or snored regularly. This observation raises the possibility that sleep apnea and its attendant intermittent hypoxemia may contribute to cancer risk. CITATION: Zhang X; Giovannucci EL; Wu K; Gao X; Hu F; Ogino S; Schernhammer ES; Fuchs CS; Redline S; Willett WC; Ma J. Associations of self-reported sleep duration and snoring with colorectal cancer risk in men and women. SLEEP 2013;36(5):681-688.
Sleep 01/2013; 36(5):681-8. · 5.05 Impact Factor
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Jennifer H Lin,
Shumin M Zhang,
Kathryn M Rexrode,
Joann E Manson,
Andrew T Chan, Kana Wu,
Shelley S Tworoger,
Susan E Hankinson,
Charles Fuchs,
J Michael Gaziano,
Julie E Buring,
Edward Giovannucci
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ABSTRACT: BACKGROUND & AIMS: There is observational and clinical evidence that indicate that sex hormones affect development of colorectal cancer (CRC) in men and women. However, the relationship between endogenous sex hormone levels and CRC is unclear. METHODS: We collected data on lifestyle, medical history, and diet etc. (through 2008), along with blood samples, from the Nurses' Health Study, the Women's Health Study, the Health Professional Follow-Up Study, and the Physicians' Health Study II. We measured plasma levels of estrone, estradiol, testosterone, sex hormone binding globulin (SHBG), and c-peptide among 730 women (293 cases of CRC and 437 healthy individuals, as controls) and 1158 men (439 CRC cases and 719 controls), and used unconditional logistic regression to estimate relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were 2-sided. RESULTS: Total testosterone, SHBG, and the ratio of estradiol to testosterone were associated with CRC in men after adjustments for matching and risk factors for CRC, including BMI and plasma levels of C-peptide. The RRs in the highest relative to the lowest quartile were 0.62 for testosterone (95% CI, 0.40-0.96), 0.65 for SHBG (95% CI, 0.42-0.99), and 2.63 for the ratio (95% CI, 1.58-4.36) (P-values for trend ≤0.02). However, in women, only the ratio of estradiol to testosterone was (inversely) associated with CRC after adjustments for all factors (RR, 0.43; 95% CI, 0.22-0.84; P-value for trend, .03). CONCLUSIONS: Based on combined data from 4 population studies, there appears to be an association between levels of sex hormones and CRC risk in men. There also appears to be an inverse association between the ratio of estradiol to testosterone and CRC in postmenopausal women.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 11/2012; · 5.64 Impact Factor
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ABSTRACT: The relation between vitamin B-6 intake and colorectal cancer risk remains uncertain.
We prospectively evaluated whether a higher vitamin B-6 intake in the remote past is more strongly associated with a lower risk of colorectal cancer than is an intake in the recent past in the Nurses' Health Study and the Health Professionals Follow-Up Study.
We assessed vitamin B-6 intake every 4 y by using validated food-frequency questionnaires and followed 86,440 women and 44,410 men for ≤28 y. Cox proportional hazards regression was used to estimate multivariable RRs and 95% CIs.
The total vitamin B-6 intake was significantly associated with an ∼20-30% lower risk of colorectal cancer in age-adjusted results, but this association became attenuated and nonsignificant after additional adjustment for nondietary and dietary factors. When the highest to lowest quintiles of cumulative total vitamin B-6 intake were compared, RRs (95% CIs) for colorectal cancer were 0.99 (0.80, 1.24; P-trend = 0.55) for women and 0.95 (0.73, 1.23; P-trend = 0.75) for men. For the same comparison, RRs were 0.92 (0.73, 1.16) for total vitamin B-6 intake 0-4 y before diagnosis, 0.99 (0.78, 1.26) for intake 4-8 y before diagnosis, 0.92 (0.71, 1.21) for intake 8-12 y before diagnosis, and 0.93 (0.69, 1.26) for intake 12-16 y before diagnosis in women. Corresponding RRs for men were 0.86 (0.63, 1.17), 0.96 (0.70, 1.32), 0.90 (0.63, 1.29), and 1.16 (0.75, 1.79). Results did not differ by cancer subsite, source of vitamin B-6 (food or supplement), alcohol consumption, or folate intake.
Our data do not support a strong role of adulthood vitamin B-6 intake in colorectal carcinogenesis in these US health professionals.
American Journal of Clinical Nutrition 08/2012; 96(4):874-81. · 6.67 Impact Factor
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Paul Lochhead,
Yu Imamura,
Teppei Morikawa,
Aya Kuchiba,
Mai Yamauchi,
Xiaoyun Liao,
Zhi Rong Qian,
Reiko Nishihara, Kana Wu,
Jeffrey A Meyerhardt,
Charles S Fuchs,
Shuji Ogino
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ABSTRACT: BACKGROUND: Evidence suggests that insulin-like growth factor 2 messenger RNA binding protein 3 (IGF2BP3, also known as IMP3) represents a promising cancer biomarker. However, the clinical, pathological, molecular and prognostic features of IGF2BP3-positive colorectal cancers remain uncertain. MATERIALS AND METHODS: We evaluated IGF2BP3 expression by immunohistochemistry in 671 rectal and colon cancer cases that form part of a molecular pathological epidemiology database. Cox proportional hazards regression models were used to compute mortality hazard ratio (HR), adjusting for clinical, pathological and molecular features, including microsatellite instability, the CpG island methylator phenotype, LINE-1 methylation and KRAS, BRAF and PIK3CA mutations. RESULTS: Among 671 colorectal cancers, 234 (35%) tumours were positive for IGF2BP3. In contrast, normal colorectal epithelium was negative for IGF2BP3 in all 403 specimens of normal mucosa adjacent to carcinoma. IGF2BP3 positivity was associated with poor differentiation (p=0.0003), stage III-IV disease (p=0.0081), BRAF mutation (p=0.031), and LINE-1 hypomethylation (p=0.020). IGF2BP3 positivity was significantly associated with shorter colorectal cancer-specific [log-rank p<0.0001; multivariate HR, 1.37; 95% confidence interval (CI), 1.02-1.84] and overall survival (log-rank p=0.0004; multivariate HR, 1.32; 95% CI, 1.05-1.66). CONCLUSIONS: IGF2BP3 expression in colorectal cancer is associated with adverse clinical outcome. Our findings support a role for IGF2BP3 as a diagnostic and/or prognostic biomarker in colorectal cancer.
European journal of cancer (Oxford, England: 1990) 07/2012; · 4.12 Impact Factor
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ABSTRACT: The results of most case-control studies have suggested a positive association between eating frequency and colorectal cancer risk. Because no prospective cohort studies have done so to date, the authors prospectively examined this association. In 1992, eating frequency was assessed in a cohort of 34,968 US men in the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for various levels of eating frequency. Effect modifications by overall dietary quality (assessed using the Diet Approaches to Stop Hypertension score) and by factors that influence insulin resistance were further assessed. Between 1992 and 2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing the highest eating frequency category (5-8 times/day) with the reference category (3 times/day), the authors found no evidence of an increased risk of colorectal cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26) or colon cancer (multivariate relative risk = 0.78, 95% confidence interval: 0.49, 1.25). There was an implied inverse association with eating frequency among participants who had healthier diets (high Diet Approaches to Stop Hypertension score; P for interaction = 0.01), especially among men in the high-insulin-sensitivity group (body mass index (weight (kg)/height (m)(2)) <25, ≥2 cups of coffee/day, and more physical activity; P for interaction < 0.01, P for trend = 0.01). There was an implied protective association between increased eating frequency of healthy meals and colorectal cancer risk and in men with factors associated with higher insulin sensitivity.
American journal of epidemiology 03/2012; 175(7):664-72. · 5.59 Impact Factor
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ABSTRACT: Epidemiological and other evidence suggests that vitamin D may be protective against several chronic diseases. Assessing vitamin D status in epidemiological studies, however, is challenging given finite resources and limitations of commonly used approaches. Using multivariable linear regression, we derived predicted 25-hydroxyvitamin D (25(OH)D) scores based on known determinants of circulating 25(OH)D, including age, race, UV-B radiation flux at residence, dietary and supplementary vitamin D intakes, BMI, physical activity, alcohol intake, post-menopausal hormone use (women only) and season of blood draw, in three nationwide cohorts: the Nurses' Health Study, Nurses' Health Study II and the Health Professionals Follow-up Study. The model r2 for each cohort ranged from 0·25 to 0·33. We validated the prediction models in independent samples of participants from these studies. Mean measured 25(OH)D levels rose with increasing decile of predicted 25(OH)D score, such that the differences in mean measured 25(OH)D between the extreme deciles of predicted 25(OH)D were in the range 8·7-12·3 ng/ml. Substituting predicted 25(OH)D scores for measured 25(OH)D in a previously published case-control analysis of colorectal cancer yielded similar effect estimates with OR of approximately 0·8 for a 10 ng/ml difference in either plasma or predicted 25(OH)D. We conclude that these data provide reasonable evidence that a predicted 25(OH)D score is an acceptable marker for ranking individuals by long-term vitamin D status and may be particularly useful in research settings where biomarkers are not available for the majority of a study population.
The British journal of nutrition 01/2012; · 3.45 Impact Factor
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ABSTRACT: Although blood donations may reduce body iron stores, to date, prospective data on frequent blood donation and colorectal cancer risk are limited.
We tested whether frequent blood donation is associated with a lower risk of colorectal cancer in the Health Professionals Follow-up Study. We prospectively followed 35,121 men who provide the information on lifetime number of blood donations in 1992 through 2008. Serum ferritin levels were measured in a random sample of 305 men. Cox proportional hazard regression models were used to calculate the multivariable relative risks (RRs, 95%CIs) after adjusting for age and other established colorectal cancer risk factors. We documented 684 incident colorectal cancer cases and 224 deaths from colorectal cancer. The mean serum ferritin levels varied from 178 µg/L for men who did not donate blood to 98 µg/L for men who had at least 30 donations. Age-adjusted results for both incidence and mortality were essentially the same as the multivariable-adjusted results. Comparing with non-donors, the multivariable RRs (95%CIs) for colorectal cancer incidence were 0.92 (0.77, 1.11) for 1-5 donation, 0.85 (0.64, 1.11) for 6-9 donations, 0.96 (0.73, 1.26) for 10-19 donations, 0.91 (0.63, 1.32) for 20-29 donations, and 0.97 (0.68, 1.38) for at least 30 donations (P(trend) = 0.92). The multivariable RRs for colorectal cancer mortality were 0.99 (0.72, 1.36) for 1-5 donation, 0.93 (0.57, 1.51) for 6-9 donations, 0.85 (0.50, 1.42) for 10-19 donations, and 1.14 (0.72, 1.83) for at least 20 donations (P(trend) = 0.82). The results did not vary by cancer sub-sites, intake levels of total iron, heme iron, or family history of colorectal cancer.
Frequent blood donations were not associated with colorectal cancer incidence and mortality in men. Our results do not support an important role of body iron stores in colorectal carcinogenesis.
PLoS ONE 01/2012; 7(6):e39319. · 4.09 Impact Factor
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ABSTRACT: Although laboratory studies linked zinc and heme iron to colorectal cancer, epidemiologic evidence is limited. We prospectively examined these associations in the Nurses' Health Study and Health Professionals Follow-up Study. We used Cox proportional hazards regression analyses to calculate cohort-specific relative risks (RRs) and pooled results using a fixed-effects model. We documented 2,114 incident colorectal cancer cases during up to 22 years of follow-up. Compared highest to lowest quintile of dietary zinc intake, the pooled multivariable RRs (95% CIs) were 0.86 (0.73, 1.02) for colorectal cancer, 0.92 (0.76, 1.11) for colon cancer, and 0.68 (0.47, 0.99) for rectal cancer. The significant inverse association between dietary zinc intake and risk of rectal cancer was mainly driven by data in women, although the difference in the sex-specific results was not statistically significant. For the same comparison, the pooled multivariable RRs (95% CIs) for heme iron were 1.10 (0.93, 1.30) for colorectal cancer, 1.06 (0.88, 1.29) for colon cancer, and 1.20 (0.83, 1.75) for rectal cancer. These associations were not significantly modified by alcohol consumption, body mass index, physical activity, menopausal status, or postmenopausal hormone use. Total zinc intake, total iron intake, dietary iron intake, and zinc or iron supplement uses were largely not associated with colorectal cancer risk. Our study does not support strong roles of zinc and heme iron intake in colorectal cancer risk; however, a suggestive inverse association of dietary zinc intake with rectal cancer risk in women requires further study.
Cancer Causes and Control 09/2011; 22(12):1627-37. · 2.88 Impact Factor
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ABSTRACT: The latest report by the World Cancer Research Fund/American Institute of Cancer Research concluded that there is convincing evidence that adult height and obesity are risk factors for colorectal cancer. However, studies relating body fatness during early life to the risk of colorectal cancer or adenoma are scarce. In the Nurses' Health Study II, participants recalled adult attained height and body shape at ages 5, 10, and 20 years (using a 9-level pictogram: 1 = most lean body shape, 9 = most overweight body shape) at baseline. Among 32,707 women who had at least one lower bowel endoscopy between 1991 and 2005, 2,327 colorectal adenomas were documented. Adult height was positively associated with risk of colorectal adenoma (multivariate OR per 2 inch increment 1.05, 95% CI: 1.01-1.09). Comparing women who were overweight (body shape level 6 or higher) to women who were most lean (body shape level 1), ORs (95% CI, P(trend)) of colorectal adenoma for body shapes at ages 5, 10, and 20 years were 1.44 (1.04-1.99, 0.01), 1.21 (0.93-1.56, 0.05), and 1.03 (0.74-1.42, 0.58), respectively. Adjustment for adult body mass index did not change results substantially. The positive associations for body fatness at ages 5 and 10 years as well as adult height were restricted to distal adenoma, while not seen for proximal or rectal adenoma. Higher height and body fatness during childhood was associated with increased risk of distal adenoma later in life, independent of adult body weight.
Cancer Prevention Research 08/2011; 4(10):1710-8. · 4.91 Impact Factor
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ABSTRACT: Observational data suggest that lower folate status is associated with an increased risk of colorectal neoplasia, implying that folate may be useful as a chemopreventive agent. We conducted a combined analysis of three large randomized trials of folic acid supplementation for the prevention of metachronous adenomas in patients with an adenoma history. Participants included 2,632 men and women who had a history of adenomas randomized to either 0.5 or 1.0 mg/day of folic acid or placebo and who had a follow-up endoscopy 6 to 42 months after randomization [mean = 30.6 (standard deviation = 8.1) months]. We used random-effects meta-analysis to estimate risk ratios (RRs) and 95% confidence intervals (CIs). The RR comparing folic acid versus placebo was 0.98 (95% CI = 0.82-1.17) for all adenomas and 1.06 (95% CI = 0.81-1.39) for advanced lesions. Folic acid was associated with a nonsignificant decreased risk of any adenoma among subjects in the lowest quartile of baseline plasma folate (≤ 11 nmol/L) and no effect among individuals in the highest quartile (> 29 nmol/L, p for trend = 0.17). There was a nonsignificant trend of decreasing risk of any adenoma associated with folic acid supplements with increasing alcohol intake. During the early follow-up reported here, more deaths occurred in the placebo group than in the folic acid group (1.7% vs. 0.5%, p = 0.002). In conclusion, after up to 3.5 years of folic acid use, there is no clear decrease or increase in the occurrence of new adenomas in patients with a history of adenoma.
International Journal of Cancer 07/2011; 129(1):192-203. · 5.44 Impact Factor
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ABSTRACT: Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study.
American journal of epidemiology 06/2011; 174(4):459-67. · 5.59 Impact Factor
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ABSTRACT: It remains unknown whether increased risk with low levels of vitamin D is present for colon and/or rectal cancer. To investigate the association between circulating vitamin D levels and colon and rectal cancer, we examined the associations between plasma levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and colon and rectal cancer in the Physicians' Health Study and then conducted a meta-analysis of eight prospective studies of circulating levels of 25(OH)D and colon and rectal cancers, including the Physicians' Health Study. Study-specific ORs and 95% CIs were pooled by using a random-effects model. A total of 1,822 colon and 868 rectal cancers were included in the meta-analysis. We observed a significant inverse association for colorectal cancer (OR = 0.66; 95% CI, 0.54-0.81), comparing top versus bottom quantiles of circulating 25(OH)D levels. The inverse association was stronger for rectal cancer (OR = 0.50 for top versus bottom quantiles; 95% CI, 0.28-0.88) than colon cancer (OR = 0.77; 95% CI, 0.56-1.07; P value for difference between colon and rectal cancer = 0.20). These data suggest an inverse association between circulating 25(OH)D levels and colorectal cancer, with a stronger association for rectal cancer.
Cancer Prevention Research 03/2011; 4(5):735-43. · 4.91 Impact Factor
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ABSTRACT: Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide have been implicated in colorectal carcinogenesis. However, in contrast to vitamin D IGF-1 is not an easily modifiable risk factor.
Combining data from the Health Professionals Follow up Study (HPFS) and the Nurses' Health Study cohort (NHS) additive and multiplicative interactions were examined between plasma 25-hydroxyvitamin D (25(OH)D) and IGF-1, IGFBP-3 as well as C-peptide levels in 499 cases and 992 matched controls. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively.
Compared to participants with high 25(OH)D and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF-1/IGFBP-3 ratio were at elevated risk of colorectal cancer when 25(OH)D was low (odds ratio (OR): 2.05 (95% CI: 1.43 to 2.92), but not when 25(OH)D was high (OR:1.20 (95% CI: 0.84 to 1.71, p(interaction): additive =0.06, multiplicative =0.25). Similarly, compared to participants with high 25(OH)D and low molar IGF-1/IGFBP-3 ratio and low C-peptide levels (reference group), participants with a combination of either high IGF-1/IGFBP-3 ratio or high C-peptide were at elevated risk for colorectal cancer when 25(OH)D was low (OR =1.90, 95% CI: 1.22 to 2.94) but not when 25(OH)D was high (OR=1.15, 95% CI: 0.74 to 1.77, p(interaction): additive=0.004; multiplicative=0.04).
The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP-3 ratio or C-peptide levels.
PLoS ONE 01/2011; 6(12):e28520. · 4.09 Impact Factor
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ABSTRACT: Experimental and observational studies have suggested that folate may play dual roles in colorectal cancer risk depending on the timing and dose.
We examined the latency between folate intake and the incidence of colorectal cancer.
We prospectively examined associations between folate intake assessed every 2 to 4 y by using validated food-frequency questionnaires and risk of colorectal cancer and adenoma in the Nurses' Health Study and Health Professionals Follow-Up Study, which included 2299 incident colorectal cancers and 5655 colorectal adenomas from 1980 to 2004.
There was an association between total folate intake 12-16 y before diagnosis and lower risk of colorectal cancer (relative risk: 0.69; 95% CI: 0.51, 0.94; ≥800 compared with <250 μg folate/d), but there was no association between intake in the recent past and colorectal cancer risk. Long- and short-term intakes of total folate were associated with a lower risk of colorectal adenoma, with a strong association with intake 4-8 y before diagnosis (odds ratio: 0.68; 95% CI: 0.60, 0.78; ≥800 compared with <250 μg folate/d). The current use of multivitamins for >15 y, but not a shorter duration of use, was associated with lower risk of colorectal cancer; and a shorter duration of use was related to lower risk of adenoma. We did not observe an adverse effect of total folate or synthetic folic acid on risk of colorectal cancer or adenoma even during the folic acid fortification era.
Folate intake is inversely associated with risk of colorectal cancer only during early preadenoma stages.
American Journal of Clinical Nutrition 01/2011; 93(4):817-25. · 6.67 Impact Factor
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ABSTRACT: Although the Mediterranean diet has been studied for cancer mortality and the Dietary Approaches to Stop Hypertension (DASH) diet shares similarities with the Mediterranean diet, few studies have specifically examined these 2 diets and incident colorectal cancer.
The objective was to prospectively assess the association between the Alternate Mediterranean Diet (aMed) and the DASH-style diet scores and risk of colorectal cancer in middle-aged men and women.
A total of 87,256 women and 45,490 men (age 30-55 y for women and 40-75 y for men at baseline) without a history of cancer were followed for ≤ 26 y. The aMed and DASH scores were calculated for each participant by using dietary information that was assessed ≤ 7 times during follow-up. Relative risks (RRs) for colorectal cancer were computed with adjustment for potential confounders.
We documented 1432 cases of incident colorectal cancer among women and 1032 cases in men. Comparing top with bottom quintiles of the DASH score, the pooled RR for total colorectal cancer was 0.80 (95% CI: 0.70, 0.91; P for trend = 0.0001). The corresponding RR for DASH score and colon cancer was 0.81 (95% CI: 0.69, 0.95; P for trend = 0.002). There was a suggestion of an inverse association with rectal cancer with a pooled RR of 0.73 (95% CI: 0.55, 0.98; P for trend = 0.31) when comparing top with bottom quintiles of DASH score. No association was observed with aMed score.
Adherence to the DASH diet (which involves higher intakes of whole grains, fruit, and vegetables; moderate amounts of low-fat dairy; and lower amounts of red or processed meats, desserts, and sweetened beverages) was associated with a lower risk of colorectal cancer.
American Journal of Clinical Nutrition 12/2010; 92(6):1429-35. · 6.67 Impact Factor
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ABSTRACT: Mutagenic compounds produced when meats are cooked at high temperatures have been hypothesized to increase risk of breast cancer.
We examined the association between intakes of the heterocyclic amines (HCA) MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline), PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]), and meat-derived mutagenic (MDM) activity and risk of breast cancer using a cooking method questionnaire administered in 1996 in the Nurses' Health Study. Between 1996 and 2006, 2,317 breast cancer cases were diagnosed during 533,618 person-years.
Higher intake of HCAs or MDM was not associated with elevated risk of breast cancer [multivariate relative risk and 95% confidence interval for the highest versus lowest quintile: MeIQx: 0.90 (0.79-1.03); PhIP: 0.92 (0.80-1.05); DiMeIQx: 0.92 (0.80-1.05); and MDM: 0.98 (0.85-1.12)]. HCA or MDM was not associated with estrogen receptor-positive/progesterone receptor-positive breast cancer risk either. There was some suggestion of a decreased risk of estrogen receptor-negative/progesterone receptor-negative breast cancer with higher intakes of MeIQx, DiMeIQx, and PhIP, but none of the associations were statistically significant. There was little evidence for an interaction between intake of cruciferous vegetables and HCA or MDM intake and risk of breast cancer.
Higher consumption of mutagens from meats cooked at higher temperature and longer duration was not associated with increased risk of postmenopausal breast cancer.
Overall prospective data including results from our study do not provide support for a substantial increase in risk of breast cancer with higher intake of HCAs.
Cancer Epidemiology Biomarkers & Prevention 05/2010; 19(5):1301-10. · 4.12 Impact Factor
