Showing papers by "Edward Giovannucci published in 2003"
TL;DR: These cross-sectional analyses show that sexual dysfunction is common, particularly among older men, and that erectile dysfunction among patients with prostate cancer is commonly associated with therapy rather than with the systemic causes thought to account for most other cases of the disorder.
Abstract: After age 50, many aspects of male sexual function decline sharply with each additional decade of age. In this study, several modifiable health behaviors were associated with erectile function. Phy...
763 citations
TL;DR: Higher plasma levels of folate and possibly vitamin B(6) may reduce the risk of developing breast cancer and achieving adequate circulating levels of Folate may be particularly important for women at higher risk ofdeveloping breast cancer because of higher alcohol consumption.
Abstract: Background: In several epidemiologic investigations, folate intake has appeared to reduce the elevated risk of breast cancer associated with moderate alcohol consumption. However, data relating plasma folate levels to breast cancer risk are sparse. We investigated the association between plasma folate and other vitamins with breast cancer in a prospective, nested case–control study. Methods: Blood samples were obtained during 1989 and 1990 from 32 826 women in the Nurses’ Health Study who were followed through 1996 for the development of breast cancer. We identified 712 breast cancer case patients and selected 712 individually matched control subjects. Dietary information was obtained using food frequency questionnaires given in 1980, 1984, 1986, and 1990. Logistic regression was used to estimate the relative risks (RRs) of breast cancer (after adjustment for potential risk factors), and a generalized linear model was used to calculate the Pearson correlation coefficients between plasma estimates of folate, vitamin B6, vitamin B12, and homocysteine, and intakes of folate, vitamin B6, and vitamin B12. All statistical tests were two-sided. Results: The multivariable RR comparing women in the highest quintile of plasma folate with those in the lowest was 0.73 (95% confidence interval [CI] = 0.50 to 1.07; Ptrend = .06). The inverse association between plasma folate and breast cancer risk was highly statistically significant among women consuming at least 15 g/day (i.e., approximately 1 drink/day) of alcohol (multivariable RR = 0.11, 95% CI = 0.02 to 0.59 for highest versus lowest quintile) in contrast with that of women consuming less than 15 g/day (multivariable RR = 0.72, 95% CI = 0.49 to 1.05). The multivariable RR comparing women in the highest quintile of plasma vitamin B6 levels with those in the lowest quintile was 0.70 (95% CI = 0.48 to 1.02; Ptrend = .09). Plasma vitamin B12 levels were inversely associated with breast cancer risk among premenopausal women (multivariable RR = 0.36, 95% CI = 0.15 to 0.86 for highest versus lowest quintile) but not among postmenopausal women. Plasma homocysteine was not associated with breast cancer risk. Conclusions: Higher plasma levels of folate and possibly vitamin B6 may reduce the risk of developing breast cancer. Achieving adequate circulating levels of folate may be particularly important for women at higher risk of developing breast cancer because of higher alcohol consumption. [J Natl Cancer Inst 2003;95:373–80]
341 citations
TL;DR: Moderate physical activity and increasing fiber intake are associated with substantial reduction in the prevalence of constipation in women, and current smoking and alcohol use were inversely associated with constipation.
292 citations
Journal Article•
TL;DR: It is found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer, and intake of marine fatty acids from food showed a similar but weaker association.
Abstract: Experimental studies suggest that marine fatty acids have an antitumor effect on prostate tumor cells. The aim of this study was to investigate whether high consumption of fish and marine fatty acids reduces the risk of prostate cancer in humans. We followed 47882 men participating in the Health Professionals Follow-up Study. Dietary intake was assessed in 1986, 1990, and 1994, using a validated food frequency questionnaire. During 12 years of follow-up, 2482 cases of prostate cancer were diagnosed, of which 617 were diagnosed as advanced prostate cancer including 278 metastatic prostate cancers. Eating fish more than three times per week was associated with a reduced risk of prostate cancer, and the strongest association was for metastatic cancer (multivariate relative risk, 0.56; 95% confidence interval, 0.37-0.86, compared with infrequent consumption, i.e., less than twice per month). Intake of marine fatty acids from food showed a similar but weaker association. Each additional daily intake of 0.5 g of marine fatty acid from food was associated with a 24% decreased risk of metastatic cancer. We found that men with high consumption of fish had a lower risk of prostate cancer, especially for metastatic cancer. Marine fatty acids may account for part of the effect, but other factors in fish may also play a role.
284 citations
Journal Article•
TL;DR: In this generally well-nourished population of middle-aged to elderly men, plasma IGF-I and IGF:IGF-binding protein-3 molar ratio tended to increase with higher intake of protein and minerals, including potassium, zinc, magnesium, calcium, and phosphorus.
Abstract: The insulin-like growth factor (IGF) axis may play opposing roles in health and disease. The age-related declines in growth hormone and IGF-I may be associated with potentially deleterious changes in body composition and functioning, but recent studies suggest that IGF-I levels may be related to risk of prostate, colorectal, premenopausal breast, and possibly other cancers. Thus, we studied dietary influences on plasma IGF-I and IGF-I: IGF-binding protein-3 ratio in 753 men in the Health Professionals Follow-Up Study who completed a food frequency questionnaire. In this generally well-nourished population of middle-aged to elderly men, plasma IGF-I and IGF-I:IGF-binding protein-3 molar ratio tended to increase with higher intake of protein and minerals, including potassium, zinc, magnesium, calcium, and phosphorus. Men with relatively high intakes of total protein (top quintile) and minerals (top quintile of the five minerals combined) had a 25% higher mean plasma level of IGF-I compared with those in the low quintiles simultaneously. The major sources of animal protein, including milk, fish, and poultry, but not red meat, as well as total vegetable protein, were associated with an increase in IGF-I levels. Energy intake was positively related to plasma IGF-I level but only in men with body mass index <25 kg/m 2 . The age-related decline in plasma IGF-I may be exacerbated by low intakes of protein and minerals. The potential role of these dietary factors on cancer risk through altering IGF-I levels requires study.
271 citations
TL;DR: The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations, and may help explain some of the epidemiologic patterns observed for these cancers.
Abstract: The incidence of colon, pancreatic, and kidney cancers, as well as aggressive prostate cancer in men, and breast and endometrial cancer in women is invariably high in Western countries. Nutritional and related factors have been typically implicated. This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk. The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations. This hypothesis may help explain some of the epidemiologic patterns observed for these cancers, both from a cross-national perspective and within populations. Of particular importance is that some of relevant factors are modifiable through nutritional and lifestyle interventions. Out of a variety of perspectives presented, nutritional manipulation through the insulin pathway may be more feasible than attempting to influence total IGF-1 concentrations, which are determined largely by growth hormone. Further study is required to test these conclusions.
266 citations
TL;DR: A significant positive association between the Western dietary pattern and the risk of colon cancer is found.
Abstract: Background:Severalfoodsandnutrientshavebeenimplicated in the development of colon and rectal cancers. In this study, we prospectively assessed the associations between major dietary patterns and the risks of these 2 cancers in women. Methods: Using dietary information collected in 1984, 1986, 1990, and 1994 from 76402 women aged 38 to 63 years without a history of cancer in 1984, we conducted factor analysis and identified 2 major dietary patterns: “prudent”and“Western.”Wecalculatedfactorscoresfor each participant and examined prospectively the associations between dietary patterns and colon and rectal cancer risks.
266 citations
TL;DR: The hypothesis that androgens may play a more direct role for early-onset or hereditary prostate cancers than for sporadic prostate cancers is suggested, because obesity is associated with lower circulating concentrations of testosterone.
Abstract: The relationship between body mass index (BMI) and prostate cancer risk may be complex because obesity is associated with various hormonal factors and because the influence of BMI may differ according to whether the cancers are hereditary or sporadic. We used data from the Health Professionals Follow-Up Study, in which 2896 incident cases of prostate cancer were reported from February 1, 1986, through January 31, 2000, to determine prospectively whether BMI was associated with the risk of hereditary (men or =60 years of age and without such a family history) prostate cancer. The risk of prostate cancer in men with a higher BMI (> or =30 kg/m2) was lower than that in men with a lower BMI (23-24.9 kg/m2) but only if they were younger (<60 years old) (relative risk = 0.52, 95% confidence interval = 0.33 to 0.83; P(trend)<.001) or had a family history of prostate cancer (relative risk = 0.74, 95% confidence interval = 0.45 to 1.19; P(trend) =.01). However, for groups with more sporadic cancers, BMI had a weak, non-statistically significant positive association with prostate cancer. We observed statistically significant interactions between BMI and age (P(interaction)<.001, two-sided Wald test) and between BMI and family history of prostate cancer (P(interaction) =.006, two-sided Wald test). Patterns for BMI and waist circumference were similar. Because obesity is associated with lower circulating concentrations of testosterone, our results suggest the hypothesis that androgens may play a more direct role for early-onset or hereditary prostate cancers than for sporadic prostate cancers.
255 citations
TL;DR: The findings, that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation.
Abstract: The high concentration of zinc in the prostate suggests that zinc may play a role in prostate health. We examined the association between supplemental zinc intake and prostate cancer risk among 46 974 U.S. men participating in the Health Professionals Follow-Up Study. During 14 years of follow-up from 1986 through 2000, 2901 new cases of prostate cancer were ascertained, of which 434 cases were diagnosed as advanced cancer. Supplemental zinc intake at doses of up to 100 mg/day was not associated with prostate cancer risk. However, compared with nonusers, men who consumed more than 100 mg/day of supplemental zinc had a relative risk of advanced prostate cancer of 2.29 (95% confidence interval = 1.06 to 4.95; P(trend) =.003), and men who took supplemental zinc for 10 or more years had a relative risk of 2.37 (95% confidence interval = 1.42 to 3.95; P(trend)<.001). Although we cannot rule out residual confounding by supplemental calcium intake or some unmeasured correlate of zinc supplement use, our findings, that chronic zinc oversupply may play a role in prostate carcinogenesis, warrant further investigation.
249 citations
Journal Article•
TL;DR: It is suggested that future studies of cruciferous vegetables should focus on early stages of prostate cancer, as well as for advanced cancers in older men, which were probably initiated decades in the past, recent dietary intakes of crucifierous vegetables may be irrelevant.
Abstract: High intake of cruciferous vegetables may offer some protection against prostate cancer, but overall data are inconclusive. Thus, we examined the association between cruciferous vegetable intake and risk of prostate cancer in the Health Professionals Follow-Up Study. Between 1986 and 2000, 2,969 cases of nonstage T1a prostate cancer were diagnosed in 47,365 men who completed dietary assessments in 1986, 1990, and 1994. We calculated the multivariate relative risk (RR) and 95% confidence intervals (CIs) using Cox regression. Overall, we found no appreciable association between baseline intake of cruciferous vegetables and risk of prostate cancer (RR, 0.93; 95% CI, 0.82-1.05, for > or = 5 versus < or = 1 serving/week; P for trend = 0.30), and only a slight suggestive association for organ-confined prostate cancer (RR, 0.88; 95% CI, 0.74-1.05; P for trend = 0.06). The inverse association was stronger for men under the age of 65 years (RR, 0.81; 95% CI, 0.64-1.02; P for trend = 0.02), especially for organ-confined cancers (RR, 0.72; 95% CI, 0.54-0.97; P for trend = 0.007). In addition, this inverse association was stronger when we restricted the analysis to men with more consistent intake of vegetables over the 10 years before 1986, when we limited the analysis to men who had had a prostate-specific antigen test, and when we considered an 8-year time lag. This study does not provide compelling evidence of a protective influence of cruciferous vegetables on prostate cancer risk. However, if cruciferous vegetables are protective early in prostate carcinogenesis, as suggested by proposed mechanisms, we may expect stronger associations, as observed, for more remote diet for prostate-specific antigen-detected early stage (organ-confined) cancers in younger men. In contrast, for advanced cancers in older men, which were probably initiated decades in the past, recent dietary intakes of cruciferous vegetables may be irrelevant. These findings suggest that future studies of cruciferous vegetables should focus on early stages of prostate cancer.
201 citations
Harvard University1, National Institutes of Health2, Loma Linda University3, Maastricht University4, University of Minnesota5, University at Buffalo6, Netherlands Organisation for Applied Scientific Research7, Kaiser Permanente8, University of Toronto9, National Institute for Health and Welfare10, Yeshiva University11
TL;DR: Elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake, however, the primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation.
Abstract: Inverse associations between fruit and vegetable consumption and lung cancer risk have been consistently reported. However, identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies. We analyzed fruit and vegetable groups using standardized exposure and covariate definitions in 8 prospective studies. We combined study-specific relative risks (RRs) using a random effects model. In the pooled database, 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6-16 years across studies. Controlling for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p-value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79; 95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison, the association was weaker for total vegetable consumption (RR = 0.88; 95% CI = 0.78-1.00; p-value, test for trend = 0.12). Associations were similar between never, past, and current smokers. These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake. However, we cannot rule out the possibility that our results are due to residual confounding by smoking. The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation. © 2003 Wiley-Liss, Inc.
TL;DR: The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.
Abstract: Colorectal cancer is the second leading cause of cancer death in the United States, and the number of new cases annually is approximately equal for men and women. Several nutritional factors are likely to have a major influence on risk of this cancer. Physical inactivity and excessive adiposity, especially if centrally distributed, clearly increase the risk of colon cancer. Hyperinsulinemia may be an important underlying risk factor. In conjunction with obesity and physical inactivity, which induce a state of insulin resistance, certain dietary patterns that stimulate insulin secretion, including high intakes of red and processed meats, saturated and trans-fats, and highly processed carbohydrates and sugars, may increase the risk of colon cancer. There is evidence suggesting that some component of red meat may independently increase the risk of colorectal cancer, and some micronutrients may be important as protective agents. Currently, the evidence is strongest for folate and calcium. Folate may be especially important in alcohol drinkers because alcohol appears to increase the risk, particularly when folate intake is low. This interaction may be related to the antifolate properties of alcohol. In contrast to earlier studies, more recent epidemiologic studies have generally not supported a strong influence of dietary fiber or fruits and vegetables, although these have other health benefits, and their consumption should be encouraged. The majority of colon cancers, as well as many other conditions, may be prevented by lifestyle alterations in the intake of these nutritional factors, in addition to other factors, such as smoking.
Journal Article•
TL;DR: The hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer is supported.
Abstract: Intake of calcium and/or dairy products has been associated with increased risk of prostate cancer in some epidemiological studies. One potential biological mechanism is that high calcium intake down-regulates 1,25 dihydroxy vitamin D3, which may increase cell proliferation in the prostate. We examined the association between calcium, dairy intake, and prostate cancer incidence in the Cancer Prevention Study II Nutrition Cohort, a prospective cohort of elderly United States adults. Participants in the study completed a detailed questionnaire on diet, medical history, and lifestyle at enrollment in 1992–1993. After excluding men with a history of cancer or incomplete dietary information, 65,321 men remained for analysis. During follow-up through August 31, 1999, we documented 3811 cases of incident prostate cancer. Multivariate-adjusted rate ratios (RRs) were calculated using Cox proportional hazards models. Total calcium intake (from diet and supplements) was associated with modestly increased risk of prostate cancer [RR = 1.2, 95% confidence interval (CI) = 1.0–1.6 for ≥2000 versus <700 mg/day, P trend = 0.02). High dietary calcium intake (≥2000 versus <700 mg/day) was also associated with increased risk of prostate cancer (RR = 1.6, 95% CI = 1.1–2.3, P trend = 0.10), although moderate levels of dietary calcium were not associated with increased risk. Dairy intake was not associated with prostate cancer risk. The association between prostate cancer and total calcium intake was strongest for men who reported not having prostate-specific antigen testing before 1992 (RR = 1.5, 95% CI = 1.1–2.0, P trend < 0.01 for ≥ 2000 mg/day of total calcium; RR = 2.1, 95% CI = 1.3–3.4 ≥2000 mg/day of dietary calcium, P trend = 0.04). Our results support the hypothesis that very high calcium intake, above the recommended intake for men, may modestly increase risk of prostate cancer.
TL;DR: The authors' data do not support previous findings that meat or saturated fat intakes are related to pancreatic cancer risk, and future prospective studies should examine the influence of cooking practices as well as other dietary habits on the risk of pancreaticcancer.
Abstract: Case-control studies suggest that meat and cholesterol intakes may be related to elevated risks of pancreatic cancer. Few prospective studies have examined associations between diet and pancreatic cancer, although in one recent study saturated fat consumption was related to higher risk. In a cohort of US women, the authors confirmed 178 pancreatic cancer cases over 18 years of follow-up. A mailed 61-item food frequency questionnaire was self-administered at baseline, and health and lifestyle variables were updated biennially. Analyses were performed using Cox proportional hazards models to adjust for potential confounders. Intakes of total fat, different types of fats, and cholesterol were not associated with pancreatic cancer risk. Similarly, total meat, red meat, and dairy products were not related to risk. Individual food items contributing to intakes of total meat and dairy products, as well as fish and eggs, did not reveal any specific association. Updating dietary exposures by using questionnaires from 1980, 1984, 1986, and 1990 produced similar findings. The authors' data do not support previous findings that meat or saturated fat intakes are related to pancreatic cancer risk. Future prospective studies should examine the influence of cooking practices as well as other dietary habits on the risk of pancreatic cancer.
Journal Article•
TL;DR: The findings that alcohol interacts with a folate-related gene (MTHFR) and that the interaction between alcohol and ADH3 is stronger among those with low folate intake support the hypothesis that the carcinogenic influence of alcohol in the large bowel is mediated through folate status.
Abstract: An increased occurrence of colorectal cancer and its adenoma precursor is observed among individuals with low intakes or circulating levels of folate, especially if alcohol intake is high, although results have not been statistically significant in all studies. We examined folate and alcohol intake and genetic polymorphisms in methylenetetrahydrofolate reductase \[ MTHFR 667→ T (ala→val) and MTHFR 1298A → C (gln→ala)\] (associated with reduced MTHFR activity) and in alcohol dehydrogenase 3 [ ADH 3 (2-2) associated with decreased alcohol catabolism] in relation to risk of colorectal adenoma in the Health Professionals Follow-Up Study. Among 379 cases and 726 controls, MTHFR genotypes were not appreciably related to risk of adenoma, but a suggestive interaction ( P = 0.09) was observed between MTHFR 677C → T and alcohol intake; men with TT homozygotes who consumed 30+ g/day of alcohol had an odds ratio (OR) of 3.52 [95% confidence interval (CI), 1.41–8.78] relative to drinkers of ≤5 g/day with the CC/CT genotypes. ADH 3 genotype alone was not appreciably related to risk, but its influence was modified by alcohol intake. Compared with fast alcohol catabolizers [ ADH 3 (1-1) ] with low intakes of alcohol (≤5 g/day), high consumers of alcohol (30+ g/day) had a marked increase in risk if they had the genotype associated with slow catabolism [ ADH 3 (2-2) ; OR, 2.94; 95% CI, 1.24–6.92] or intermediate catabolism [ ADH 3 (1-2) ] of alcohol (OR, 1.83; 95% CI, 1.03–3.26) but not if they were fast catabolizers [ ADH 3 (1-1) ; OR = 1.27; 95% CI = 0.63–2.53). In addition, an increased risk of colorectal adenoma (OR, 17.1; 95% CI, 2.1–137) was observed for those with the ADH 3 (2-2) genotype and high alcohol-low folate intake compared with those with low alcohol-high folate intake and the ADH 3 (1-1) genotype ( P for interaction = 0.006). Our results indicate that high intake of alcohol is associated with an increased risk of colorectal adenoma, particularly among MTHFR 677TT and ADH 3 (2-2) homozygotes. The findings that alcohol interacts with a folate-related gene ( MTHFR ) and that the interaction between alcohol and ADH 3 is stronger among those with low folate intake support the hypothesis that the carcinogenic influence of alcohol in the large bowel is mediated through folate status.
Journal Article•
TL;DR: No overall association was found between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with alpha-tocopherol.
Abstract: There is some evidence that α-linolenic acid might be positively related to prostate cancer risk. Associations between serum fatty acid composition as well as fatty acid intakes and prostate cancer risk were examined in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133 male smokers aged 50–69 years. During 5–8 years of follow-up, 246 prostate cancer cases were diagnosed. One control was selected and matched by age (± 1 month) for each case from the cohort subjects alive and free of prostate cancer at the time the case was diagnosed. This study included 198 case-control pairs with baseline serum sample available for both. Fatty acids of serum cholesterol esters were measured as a percentage of total fatty acids, using capillary gas chromatography. Intakes of fatty acids were assessed from a validated self-administered dietary questionnaire. Serum and dietary fatty acids had no consistent association with prostate cancer risk. Serum α-linolenic acid was not related to prostate cancer risk. Twofold risk was found in the highest quartile of serum myristic acid compared with the lowest quartile (odds ratio, 1.93; 95% confidence interval, 1.02–3.64). α-Tocopherol supplementation modified the association between serum linoleic acid and prostate cancer risk ( P for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04–0.68) in the highest quartile of serum linoleic acid compared with the lowest quartile in men who received α-tocopherol, whereas no association was found in men who did not receive α-tocopherol. In conclusion, we found no overall association between serum or dietary α-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with α-tocopherol. High serum myristic acid associated with an increased risk of prostate cancer.
Journal Article•
TL;DR: In this large prospective cohort of women, parity was associated significantly with a reduced risk of pancreatic cancer, and additional studies should examine the physiological or hormonal changes underlying pregnancy or childbirth that may explain this finding.
Abstract: Incidence rates for pancreatic cancer are consistently lower in women than in men. Previous studies suggest that reproductive factors, particularly parity, may reduce pancreatic cancer risk in women. We examined parity, breast feeding history, age at first birth, menstrual factors, and exogenous hormone use in relation to pancreatic cancer risk in a prospective cohort study of women. Information on parity and other reproductive factors was assessed by questionnaires in 1976 and updated biennially. Multivariate relative risks were adjusted for cigarette smoking, body mass index, diabetes, and height. During 22 years of follow-up (1976–1998), 115,474 women contributed 2.4 million years of person time, and 243 cases of pancreatic cancer were identified. Compared with nulliparous women, the relative risk of pancreatic cancer was 0.86 [95% confidence interval (CI), 0.55–1.36] for women with 1–2 births, 0.75 (95% CI, 0.48–1.17) for 3–4 births, and 0.58 (95% CI, 0.34–0.98) for those with ≥5 births after adjusting for other factors. An analysis for linear trend indicates a 10% reduction in risk for each birth (Ptrend = 0.008). Other reproductive factors and exogenous hormone use were not significantly related to pancreatic cancer risk. In this large prospective cohort of women, parity was associated significantly with a reduced risk of pancreatic cancer. Additional studies should examine the physiological or hormonal changes underlying pregnancy or childbirth that may explain this finding.
TL;DR: In this large prospective cohort study, a history of cholecystectomy appears to increase modestly the risk of colorectal cancer, even after adjustment for other coloreCTal cancer risk factors.
Abstract: Earlier work describes a modest association between cholecystectomy and the risk of colorectal cancer. We conducted a prospective study of 85 184 women, 36-61 years old, who had no history of cancer to evaluate whether known risk factors for colorectal cancer, including dietary history, that have not been controlled for in previous analyses can help explain the observed association. During 16 years of follow-up, 877 cases of colorectal cancer were documented and 1452 women who underwent endoscopy during the follow-up time were diagnosed with distal adenomas. After adjustment for age and other known or suspected risk factors, we found a significant, positive association between cholecystectomy and the risk of colorectal cancer (multivariate relative risk RR 1.21, 95% CI 1.01-1.46). The risk was highest for cancers of the proximal colon (RR 1.34, 95% CI 0.97-1.88) and the rectum (RR 1.58, 95% CI 1.05-2.36). However, we did not observe a significant association between cholecystectomy and distal colorectal adenomas. In this large prospective cohort study, a history of cholecystectomy appears to increase modestly the risk of colorectal cancer, even after adjustment for other colorectal cancer risk factors.
Journal Article•
TL;DR: The testable hypothesis that the elevated risk of clinically important prostate cancer in men with a high energy intake may be attributable to certain metabolic profiles that favor enhanced growth factor production over an increase in adiposity is suggested.
Abstract: Energy restriction reduces prostate tumor growth in transplantable tumor models in rodents, which suggests that excessive energy intake may contribute to the risk of prostate cancer. The association of total energy intake across the normal range with prostate cancer has not been consistent in epidemiological studies. We prospectively evaluated the joint associations of energy intake and body size or physical activity with prostate cancer. Participants were 46786 male health professionals ages 40-75 years at baseline in 1986 who were free of cancer diagnosis. Between 1986 and 2000, we documented 2896 incident prostate cancer cases (excluding stage T1a) by review of medical records and histopathology reports. Of these, 339 were metastatic or fatal cases. We used Cox proportional hazards regression to estimate the multivariate relative risk (RR) of prostate cancer associated with energy intake measured using a food frequency questionnaire, overall and stratified by body mass index, waist size, physical activity, as well as by age and family history of prostate cancer. There was no association between energy intake and total prostate cancer incidence. However, a modest increased risk of metastatic or fatal disease with energy intake was suggested [RR comparing extreme quintiles: 1.38, 95% confidence interval (CI) 0.96-1.98, P(trend) = 0.06]. This association was most pronounced in men with a lower body mass index (in stratum or= median: RR = 1.74, 95% CI 0.93-3.26; P(interaction) = 0.09]. Also, the association of energy intake with metastatic and fatal prostate cancer was restricted to men who were younger [in stratum
TL;DR: In this article, the authors examined changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice.
Abstract: The consumption of tomato products is associated with a reduced risk of cardiovascular disease and several cancers. It is hypothesized that lycopene, the major carotenoid in tomato products, may mediate this relationship. We designed a study to examine changes in plasma and buccal mucosal cell (BMC) lycopene concentrations in healthy adults consuming standard daily servings of processed tomato products: spaghetti sauce, tomato soup, or vegetable juice. Thirty-six healthy subjects consumed a lycopene-free diet for 2 wk and were then assigned to one of three (n = 12) intervention groups consuming daily, single servings of sauce (21 mg lycopene per ½ cup), soup (12 mg lycopene per 1 cup), or juice (17 mg lycopene per 8 oz) for 4 wk. Fasting blood and BMC samples were evaluated by high-performance liquid chromatography analysis for carotenoids and lycopene isomers. Total plasma lycopene concentrations (Mean ± SEM) decreased from 1.05 ± 0.07 to 0.54 ± 0.05 mmol/l (49%, P < 0.0001) during the 2-wk washout perio...
TL;DR: No evidence was found that vitamins A, C and E; folate; or carotenoids play an important protective role against incident SCC, after multivariate adjustment for various known behavioral, sun‐exposure and sun‐sensitivity risk factors for SCC.
Abstract: Our objective was to examine prospectively the intake of vitamins A (including retinol and total vitamin A), C and E; folate; total carotene; and several individual carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin and lutein/zeaxanthin) in relation to incidence of SCC of the skin in 2 large cohorts of men and women. We used a prospective cohort study design with up to 14 years of follow-up in women and 10 years in men. Diet was measured with FFQs every 2-4 years; cases of SCC of the skin were ascertained on biennial questionnaires and confirmed by medical records. Participants were female nurses and male health professionals, from the Nurses' Healthy Study and the Health Professionals Follow-up Study in the United States, without a history of any cancer in 1982 (n = 85,944 women) and 1986 (n = 43,867 men). Follow-up response was achieved for over 90% of potential person-years. Relative risks and 95% confidence intervals for development of SCC of the skin are reported. We recorded 369 cases of SCC in women and 305 cases in men. After multivariate adjustment for various known behavioral, sun-exposure and sun-sensitivity risk factors for SCC, there were no significant inverse associations between these dietary factors and SCC incidence. No evidence was found that vitamins A, C and E; folate; or carotenoids play an important protective role against incident SCC.
TL;DR: Plasma concentrations of total lycopene and its most abundant isomers in samples taken 3-4 y apart were strongly correlated, indicating that dietary patterns and metabolic processes defining lycopenes concentrations are stable over time.
Abstract: Epidemiologic and laboratory studies suggest a possible role for tomato products, a rich source of the carotenoid lycopene, in the prevention of certain cancers and cardiovascular disease. Lycopene is consumed primarily as the all-trans-isomer, but the majority of lycopene in blood and tissue exists as a variety of cis-isomers. Specific isomers may be involved in different biological reactions, and patterns of isomers may provide insight into the risk or pathogenesis of disease processes. Total lycopene concentration and the concentrations of the cis- and trans-lycopene isomers were measured by HPLC in plasma samples taken 3-4 y apart from 144 mostly nonsmoking male participants in the Health Professionals Follow-up Study. Correlations between plasma concentrations determined 3-4 y apart ranged from 0.55 (all-trans-isomer) to 0.70 (cis-isomer 5 -cis) (P < 0.001). For total lycopene, the correlation was 0.63 (P < 0.001). Total cis-lycopene contributed approximately 67% of total lycopene (range 50-79%). At each time point, the various lycopene isomer concentrations were highly correlated with one another with Spearman correlation coefficients ranging from 0.90 to 0.99 (P < 0.001). Plasma concentrations of total lycopene and its most abundant isomers in samples taken 3-4 y apart were strongly correlated, indicating that dietary patterns and metabolic processes defining lycopene concentrations are stable over time. Because the patterns of lycopene isomers showed limited between-person variability, our results suggest that measuring specific lycopene isomers in epidemiologic studies may not provide additional information beyond that provided by total lycopene concentration. Single plasma samples quantitating plasma lycopene are a valid predictor of long-term exposure for epidemiologic studies.
TL;DR: Adequate folate intake may be important in the primary prevention of overall major chronic disease in women, especially among younger women consuming more than two alcoholic drinks per day.
Abstract: Alcohol interferes with folate metabolism and has opposing effects on the risks of cardiovascular disease and cancer. The authors examined the joint association of alcohol and folate intake with risk of major chronic disease, defined as fatal or nonfatal cardiovascular disease or cancer, or other nontraumatic death. This study included 83,929 women aged 34–59 years with no previous history of cardiovascular disease or cancer who provided dietary data in 1980. During 16 years of follow-up, the authors documented 10,666 new cases of major chronic disease. Overall, heavy drinkers (>30 g/day) with a lower total folate intake (<180 µg/day) had the highest risk; in comparison with abstainers with a folate intake of 400–599 µg/day, the multivariate relative risk was 1.36 (95% confidence interval: 1.10, 1.70). However, the increased risk of major chronic disease associated with heavy drinking was largely diminished among women with a higher folate intake (p for interaction = 0.02). The positive association between heavy alcohol/low folate intake and risk of major chronic disease was most apparent among women younger than age 60 years. Adequate folate intake may be important in the primary prevention of overall major chronic disease in women, especially among younger women consuming more than two alcoholic drinks per day.
TL;DR: Toenail selenium levels analyzed by neutron activation were not associated with risk of total CHD after adjustment for age and smoking and other CHD risk factors, and a specific protective role for myocardial infarction cannot be excluded.
Abstract: Selenium is a trace mineral that plays a role in antioxidant defenses as a component of glutathione peroxidase. Epidemiologic findings on the relation of selenium status to risk of heart disease are inconsistent. Therefore, the authors investigated prospectively the association between toenail selenium levels and risk of coronary heart disease (CHD) in a case-control study nested within the Health Professionals Follow-up Study. Between 1987 and 1992, 470 CHD cases were newly diagnosed. A control matched to each case on age, smoking status, and date of toenail return was chosen. Toenail selenium levels analyzed by neutron activation were not associated with risk of total CHD after adjustment for age and smoking and other CHD risk factors (highest quintile vs. lowest: odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.55, 1.32; p-trend = 0.75). Selenium level was inversely associated with risk of nonfatal myocardial infarction for extreme quintiles (OR = 0.54, 95% CI: 0.31, 0.93; p-trend = 0.07), was less so for fatal CHD (OR = 0.79, 95% CI: 0.39, 1.60; p-trend = 0.61), and was directly associated with coronary revascularization procedures (OR = 2.38, 95% CI: 1.11, 5.09; p-trend = 0.02). Although these findings suggest no overall relation between selenium status and CHD, a specific protective role for myocardial infarction cannot be excluded. coronary disease; nutrition; selenium
TL;DR: The intake of all alcoholic beverage types is inversely associated with the risk of cholecystectomy, and recommendations regarding the benefit of consuming moderate quantities of alcohol should be weighed against the potential health hazards.
TL;DR: No apparent dose-dependent association was observed for the frequency of aspirin use and lung cancer risk, and results remained null when consistent use of aspirin over time was examined.
Abstract: Evidence from animal studies suggests that aspirin and possibly other nonsteroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) inhibitors may influence the development and progression of lung cancer (Duperron and Castonguay, 1997; Rioux and Castonguay, 1998; Yao et al, 2000). As COX-2 enzymes are constitutively expressed in lung neoplastic tissue (Xu, 2002), reduced synthesis of prostaglandins from arachidonic acid by inhibition of COX-2 enzymes may have preventive or therapeutic effects in lung carcinogenesis.
Journal Article•
TL;DR: The results suggest that greater height may be associated with better survival of prostate cancer patients and that body mass index or weight is not associated with either prostate cancer death or death because of other causes.
Abstract: We investigated the associations between height and other anthropometric factors and the survival of 584 prostate cancer patients, initially recruited for a population-based, case-control study. During a median of 6.6 years of follow-up, 129 prostate cancer deaths and 153 deaths because of other causes were identified. After adjusting for age, cancer stage, and grade, the relative risk and 95% confident intervals for prostate cancer death were 1.0 (reference), 0.9 (0.6–1.4), 0.5 (0.3–0.9), and 0.6 (0.3–1.0) for patients whose heights were <1.75 m, 1.75–1.79 m, 1.80–1.84 m, and ≥1.85 m, respectively ( P for trend = 0.01). Similar associations were found in subgroup analyses by cancer stage, cancer grade, age, race, and occupation-based socioeconomic status. However, height was not associated with death because of other causes. In addition, no significant associations were found between body mass index or weight and either prostate cancer death or death because of other causes. Our results suggest that greater height may be associated with better survival of prostate cancer patients.
Journal Article•
TL;DR: PI3-K catalyzes the addition of phosphate to the phosphoinositides at the 3′-OH position of the inositol ring to target Akt kinase, an important mediator of cell-survival signals in CaP.
Abstract: PI3-K[3][1] is an important mediator of cell-survival signals in CaP [(1)][2] . PI3-K catalyzes the addition of phosphate to the phosphoinositides at the 3′-OH position of the inositol ring. These phosphorylated lipids target Akt kinase. When activated, Akt targets and inhibits a variety of
TL;DR: The results are suggestive of an elevated adenoma risk with higher fructosamine and triglyceride levels and with lower fasting insulin level, and some potential theoretical advantages of fructsamine over HbAlc in the context of studying colorectal carcinogenesis are suggested.
Abstract: Misciagna et al. [1] report the results of an interesting study of fasting serum fructosamine, glucose, insulin, and triglycerides in relation to risk of colorectal adenoma in this issue of the journal. The results are suggestive of an elevated adenoma risk with higher fructosamine and triglyceride levels and with lower fasting insulin level. The authors address some potential methodologic limitations, including selection, measurement bias and confounding. Thus, these issues will not be dealt with in this commentary. Instead, this will focus instead on the contributions of this study to our understanding of colorectal carcinogenesis. The insulin resistance or metabolic syndrome is characterized by a number of abnormalities, including dyslipidemia (low concentrations of HDL cholesterol, and elevated concentrations of triglycerides, VLDL, and small dense LDL), hypertension, chronic inflammation, procoagulation, and impaired fibrinolysis [2]. Obesity, in particular visceral adiposity, physical inactivity and a Western dietary pattern are involved in the etiology of this syndrome. The similarity of risk factors for colon cancer and for factors related to the insulin resistance syndrome was first described in detail about a decade ago [3, 4]. Since that time, an impressive body of epidemiologic data has accumulated indicating that colon cancer risk is associated with the insulin resistance syndrome. This evidence is strong from studies based on determinants of the insulin resistance syndrome (obesity, abdominal distribution of adiposity, physical inactivity), and on the major disease consequence of this syndrome, type 2 diabetes [5]. Studies of hypertriglyceridemia, hyperglycemia, and hyperinsulinemia in relation to colon cancer risk are suggestive, but not definitive at this point. For colorectal or colon cancer [6-10], and for adenoma [11, 12], a number of studies have shown a significant or borderline significant increased risk associated with hyperglycemia. Higher level of glycosylated hemoglobin (HbA1e), a marker of average glycemia over the previous 2 months, was associated with an elevated risk of colorectal cancer in one cohort study [13], but not in a smaller cohort study [14]. A novel feature of the study by Misciagna et al. is the use of fructosamine, which is an indicator of total glycated proteins in the serum, and which correlates with average blood glucose over a period of several weeks. Although HbAI is generally considered as the gold standard for measurement of glycemic control in diabetic patients, the authors suggest some potential theoretical advantages of fructosamine over HbAlc in the context of studying colorectal carcinogenesis. They cite evidence that fructosamine is glycated more rapidly than hemoglobin [15], and thus might better indicate a peak in blood glucose following a meal with high glycemic load. They also cite a study that fou d that in non-diabetics, 6 weeks of a high glycemic diet increased levels of fructosamine but not of HbA1c [16]. In addition, in a recent meta-analysis of randomized studies of low-glycemic index diets in the management of diabetes, results were stronger for a reduction of fructosamine than of HbA1~ if the duration of the study was less than 6 weeks [17]. HbA1~ measures non-enzymatic glycosylation of hemoglobin in erythrocytes, whereas fructosamine measures non-enzymatic glycation of proteins in the same compartment of plasma glucose; thus, fructosamine might better reflect plasma glucose fluctuations. A recent study indicated that the discordance between HbAjc and fructosamine in an individual is stable over time, and may possibly have some pathophysiologic relevance and not merely reflect differences in turnover of the affected proteins [18]. Clearly more study is required to better understand what physiologic aspects HbAIc and fructosamine are measuring, how they differ, and how they relate to colorectal carcinogenesis. Although HbAI is considered the gold standard for assessing glycemic control for diabetics, HbA1c may not necessarily be the superior measure of postprandial spikes from a high glycemic diet in non-diabetics, which could possibly be most relevant for the study of colorectal cancer. Because many studies of HbAIc and fructosamine have been done in diabetics, it is critical to get more information in non-diabetics. The findings from the study by Misciagni et al., while requiring confirmation, suggest that an indicator of level of glucose in the blood sensitive to foods with a high glycemic index influences colorectal carcinogenesis. A recent prospective study found that diets with a high glycemic index and load were associated with an increased risk of colon cancer [19]. However, not all studies are supportive [20]. If insulinemic rather than glycemic spikes are most etiologically relevant, the inconsistent findings for dietary glycemic index would not be surprising because the glycemia response explains only about 23% of the variability in insulinemia [21]. Besides glycemic index,