Showing papers by "Edward Giovannucci published in 1999"

Tomatoes, Tomato-Based Products, Lycopene, and Cancer: Review of the Epidemiologic Literature

Abstract: The epidemiologic literature in the English language regarding intake of tomatoes and tomato-based products and blood lycopene (a compound derived predominantly from tomatoes) level in relation to the risk of various cancers was reviewed. Among 72 studies identified, 57 reported inverse associations between tomato intake or blood lycopene level and the risk of cancer at a defined anatomic site; 35 of these inverse associations were statistically significant. No study indicated that higher tomato consumption or blood lycopene level statistically significantly increased the risk of cancer at any of the investigated sites. About half of the relative risks for comparisons of high with low intakes or levels for tomatoes or lycopene were approximately 0.6 or lower. The evidence for a benefit was strongest for cancers of the prostate, lung, and stomach. Data were also suggestive of a benefit for cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix. Because the data are from observational studies, a cause-effect relationship cannot be established definitively. However, the consistency of the results across numerous studies in diverse populations, for case-control and prospective studies, and for dietary-based and blood-based investigations argues against bias or confounding as the explanation for these findings. Lycopene may account for or contribute to these benefits, but this possibility is not yet proven and requires further study. Numerous other potentially beneficial compounds are present in tomatoes, and, conceivably, complex interactions among multiple components may contribute to the anticancer properties of tomatoes. The consistently lower risk of cancer for a variety of anatomic sites that is associated with higher consumption of tomatoes and tomato-based products adds further support for current dietary recommendations to increase fruit and vegetable consumption.

Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3

Abstract: Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in many experimental systems. Acromegalics, who have abnormally high levels of growth hormone and IGF-I, have higher rates of colorectal cancer. We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospective case-control study nested in the Physicians' Health Study. Methods: Plasma samples were collected at baseline from 14916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects. All P values are two-sided. Results: IGFBP-3 levels correlated with IGF-I levels (r = .64) and with IGF-II levels (r = .90). After controlling for IGFBP-3, age, smoking, body mass index (weight in kg/[height in m] 2 ), and alcohol intake, men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile (relative risk [RR] = 2.51; 95% confidence interval [CI] = 1.15-5.46; P for trend = .02). After controlling for IGF-I and other covariates, men with higher IGFBP-3 had a lower risk (RR = 0.28; 95% CI = 0.12-0.66 ; P for trend = .005, comparing extreme quintiles). The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men. IGF-II was not associated with risk. Conclusions: Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer.

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis.

Abstract: Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and β-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (α- and β-carotene, β-cryptoxanthin, lutein, and lycopene) plus α- and γ-tocopherol and retinol using high-performance liquid chromatography. Results for plasma β-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (CIs), and P s for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active β-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls ( P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54–1.06; P , trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34–0.91; P , trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P , trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to β-carotene supplements. However, in the β-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher α-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming β-carotene supplements. For men with low lycopene, β-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

Dietary Fiber and the Risk of Colorectal Cancer and Adenoma in Women

Abstract: Background A high intake of dietary fiber has been thought to reduce the risk of colorectal cancer and adenoma. Methods We conducted a prospective study of 88,757 women, who were 34 to 59 years old and had no history of cancer, inflammatory bowel disease, or familial polyposis, who completed a dietary questionnaire in 1980. During a 16-year follow-up period, 787 cases of colorectal cancer were documented. In addition, 1012 patients with adenomas of the distal colon and rectum were found among 27,530 participants who underwent endoscopy during the follow-up period. Results After adjustment for age, established risk factors, and total energy intake, we found no association between the intake of dietary fiber and the risk of colorectal cancer; the relative risk for the highest as compared with the lowest quintile group with respect to fiber intake was 0.95 (95 percent confidence interval, 0.73 to 1.25). No protective effect of dietary fiber was observed when we omitted adjustment for total energy intake, whe...

A Prospective Study of Folate Intake and the Risk of Breast Cancer

Abstract: ContextFolate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption.ObjectivesTo assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol.DesignProspective cohort study performed in 1980, with 16 years of follow-up.Setting and ParticipantsA total of 88,818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980.Main Outcome MeasureIncidence of invasive breast cancer by levels of folate and alcohol intake.ResultsA total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 µg/d compared with 150 to 299 µg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend=.001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 µg/d (for alcohol intake ≥15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 µg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93).ConclusionsOur findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.

Prospective Study of Adult Onset Diabetes Mellitus (Type 2) and Risk of Colorectal Cancer in Women

Abstract: Background: The remarkable similarity of lifestyle and environmental risk factors f or t ype 2 ( non-insulindependent) diabetes mellitus and colon cancer has led to the hypothesis that diabetes may increase the risk of this cancer. We prospectively examined the relationship between diabetes and risk of colorectal cancer in a cohort of 118 403 women aged 30 through 55 years who were without previously diagnosed cancer at baseline in 1976. Methods: The women, who were enrolled in the Nurses’ Health Study, were assessed for history of diabetes at baseline and during follow-up by use of biennial questionnaires. Self-reported diabetes was validated by information obtained from a supplemental questionnaire on symptoms and treatment and was confirmed by medical record review in a sample of the participants. Incident cases of colorectal cancer were ascertained through medical record review. All reported P values are twosided. Results: During 18 years of follow-up (2 001 061 person-years), we documented 892 new cases of colorectal cancer. After adjustment for age, body mass index (weight in kg/height in m 2 ), physical activity, and other covariates, relative risks (RRs) were 1.43 (95% confidence interval [CI] = 1.10‐1.87; P = .009) for colorectal cancer, 1.49 (95% CI = 1.09‐2.06; P = .01) for colon cancer, 1.11 (95% CI = 0.56‐2.21; P = .76) for rectal cancer, 1.56 (95% CI = 1.07‐ 2.28; P = .02) for advanced colorectal cancer, and 2.39 (95% CI = 1.46‐3.92; P = .0005) for fatal colorectal cancer. Conclusion: Our data provide support for the hypothesis that diabetes is associated with an increased risk of colorectal cancer in women. [J Natl Cancer Inst 1999;91:542‐7]

Fruit and Vegetable Intake and Incidence of Bladder Cancer in a Male Prospective Cohort

Abstract: Background Previous epidemiologic studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with regard to the types of fruits and vegetables consumed. We examined total fruit and vegetable intake, as well as intakes of subtypes of fruits and vegetables, in relation to bladder cancer risk in a large male prospective cohort study. Methods Two hundred fifty-two cases of incident bladder cancer were diagnosed from 1986 through January 31, 1996, among 47,909 men enrolled in the Health Professionals Follow-up Study. Each participant in this cohort completed a 131-item food-frequency questionnaire in 1986 and subsequently in 1990 and 1994. We used logistic regression analyses to examine fruit and vegetable intake in relation to bladder cancer risk, after adjusting for age, history of cigarette smoking, current smoking status, geographic region, total fluid intake, and caloric intake. Results We observed a weak, inverse association that was not statistically significant between total fruit and vegetable intake and bladder cancer risk. Intake of cruciferous vegetables was inversely associated with risk (relative risk = 0.49; 95% confidence interval = 0.32-0.75, for the highest category of cruciferous vegetable intake compared with the lowest), but intakes of yellow or green leafy vegetables or carotenoid-rich vegetables were not associated with risk. Individual cruciferous vegetables, except for coleslaw, were all inversely related to bladder cancer risk, but only the associations for broccoli and cabbage were statistically significant. Conclusions Data from this study indicate that high cruciferous vegetable consumption may reduce bladder cancer risk, but other vegetables and fruits may not confer appreciable benefits against this cancer.

Fluid intake and the risk of bladder cancer in men.

Abstract: Background Studies in animals have shown that the frequency of urination is inversely associated with the level of potential carcinogens in the urothelium. In humans, an increase in total fluid intake may reduce contact time between carcinogens and urothelium by diluting urinary metabolites and increasing the frequency of voiding. The data on fluid intake in relation to the risk of bladder cancer are inconclusive. Methods We examined the relation between total fluid intake and the risk of bladder cancer over a period of 10 years among 47,909 participants in the prospective Health Professionals Follow-up Study. There were 252 newly diagnosed cases of bladder cancer during the follow-up period. Information on total fluid intake was derived from the reported frequency of consumption of the 22 types of beverages on the food-frequency questionnaire, which was completed by each of the 47,909 participants who were free of cancer in 1986. Logistic-regression analyses were performed to adjust for known and suspect...

A polymorphism of the methionine synthase gene: association with plasma folate, vitamin B12, homocyst(e)ine, and colorectal cancer risk.

Abstract: We previously reported (J. Chen et al., Cancer Res., 56: 4862-4864, 1996; J. Ma et al., Cancer Res., 57: 1098-1102, 1997) that a 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism (677C-->T, ala-->val) was associated with lower risk of colorectal cancer. In this study, we examined the relationship of a polymorphism (2756A-->G, asp-->gly) in the gene (MTR) for methionine synthase, another important enzyme in the same folate/methionine/homocyst(e)ine metabolic pathway, with risk of colorectal cancer among 356 cases and 476 cancer-free controls. The frequency of the homozygous variant genotype (gly/gly) was slightly lower among cases (3%) than controls (5%). The odds ratio for the gly/gly genotype was 0.59 [95% confidence interval (CI), 0.27-1.27] compared with those with the homozygous wild type (asp/asp). There were no significant differences in plasma levels of folate, vitamin B12, and homocyst(e)ine (tHcy) among the MTR genotypes, in contrast to the MTHFR polymorphism. However, similar to the interaction observed for the MTHFR polymorphism among men who consumed less than 1 alcoholic drink/day, those with the gly/gly genotype had a lower risk of colorectal cancer with an odds ratio of 0.27 (95% CI, 0.09-0.81) compared with those with the asp/asp genotype. The possible association of the MTR polymorphism with lower risk of colorectal cancer especially among those with low alcohol consumption, in the same direction as for the MTHFR polymorphism, is intriguing. However, our study had limited statistical power because of the low frequency of the MTR variant genotype, which is reflected in the wide CIs. Hence, these findings need to be confirmed in larger populations.

Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States.

Abstract: Vitamin E and vitamin C supplements and specific carotenoids did not seem to cause a substantially reduced risk for stroke in a cohort of 40- to 75-year-old men who did not have a history of cardio...

Insulin-like growth factor-I and binding protein-3 and risk of cancer.

Abstract: Insulin-like growth factor (IGF)-I is an important mitogen required by some cell types to progress from the G1 phase to the S phase of the cell cycle. IGF binding proteins (IGFBPs) can have opposing actions, in part by binding IGF-I, but also by direct inhibitory effects on target cells. As mitogens and anti-apoptotic agents, IGFs may be important in carcinogenesis, possibly by increasing the risk of cellular transformation by enhancing cell turnover. Indeed, many types of neoplastic cells express or overexpress IGF-I receptors, which stimulate mitogenesis when activated by IGF-I in vitro. In vivo, tissue IGF bioactivity is determined not only by circulating IGF-I and IGFBP levels, but also by local production of IGFs, IGFBPs, and possibly IGFBP proteases that enhance IGF-I availability by cleaving IGFBPs. Because determinants of tissue IGF bioactivity appear to be regulated in parallel with circulating IGF-I level, it is reasonable to hypothesize that the substantial intraindividual variability in circulating levels of IGF-I and IGFBP-3 may be important in determining risk of some cancers. In recent epidemiologic studies, relatively high plasma IGF-I and low IGFBP-3 levels have been independently associated with greater risk of prostate cancer in men, breast cancer among premenopausal women, and colorectal adenoma and cancer in men and women and possibly lung cancer. These include prospective data from the Physicians' Health Study and the Nurses' Health Study. In general, two- to fourfold elevated risks have been observed for prostate cancer in men in the top quartile of IGF-I relative to those in the bottom quartile, and low levels of IGFBP-3 were associated with an approximate doubling of risk. For breast cancer, an association with IGF-I for postmenopausal women was not apparent, but strong associations were observed for premenopausal cases in the Nurses' Health Study. Further study is needed to confirm this subgroup finding in women. Recent data also indicate that high IGF-I and low IGFBP-3 increase risk of colorectal cancer and large or villous adenomas. Of note, for colorectal neoplasia, fourfold elevated risks were observed in men and women with low IGFBP-3, whereas high IGF-I was associated with a doubling of risk. These emerging epidemiologic data indicate that high levels of IGF-I and low levels of IGFBP-3 are associated with an increased risk of at least several types of carcinoma that are common in economically developed countries. Further study is required to determine the clinical relevance of these findings.

Supplemental Vitamin E Intake and Prostate Cancer Risk in a Large Cohort of Men in the United States

Abstract: A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finland recently reported an unexpected, strong protective effect of vitamin E against prostate cancer incidence and mortality. Our objective was to prospectively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population. In 1986, we identified 47,780 U.S. male health professionals, free from diagnosed cancer, who completed a dietary and lifestyle questionnaire; supplemental vitamin E and prostate cancer incidence were updated biennially through 1996. We estimated relative risks (RRs) from multivariate pooled logistic regression models. There were 1896 total (non-stage A1), 522 extraprostatic, and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986-1996. Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 (95% confidence interval [CI], 0.95-1.20) for total and 1.14 (95% CI, 0.82-1.59) for metastatic or fatal prostate cancer compared with those consuming none. Current use, dosage, and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk. However, among current smokers and recent quitters, those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 (95% CI, 0.18-1.07) for metastatic or fatal prostate cancer compared with nonusers. Thus, supplemental vitamin E was not associated with prostate cancer risk generally, but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation.

Recreational Physical Activity and the Risk of Cholecystectomy in Women

Abstract: Background Physical activity may be an important determinant of the risk of gallstone disease in women, both independently and as a result of its role in maintaining body weight. Methods We prospectively studied recreational physical activity (such as jogging, running, and bicycling) and sedentary behavior (such as spending hours watching television) in relation to the risk of cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 60,290 women who were 40 to 65 years of age in 1986 and had no history of gallstone disease. As part of the Nurses' Health Study, the women reported on questionnaires mailed to them every two years both their activity level and whether they had undergone cholecystectomy. During a 10-year follow-up period (1986 to 1996), 3257 cases of cholecystectomy were documented. Results Recreational physical activity was inversely related to the risk of cholecystectomy. The multivariate relative risk for women in the highest as compared with the lowest quintile of physic...

Smoking and Risk of Total and Fatal Prostate Cancer in United States Health Professionals

Abstract: Studies that have examined the relationship between cigarette use and prostate cancer incidence have yielded inconsistent results, although most studies have suggested that smoking is related to the occurrence of fatal prostate cancer. We evaluated prospectively the relationship between cigarette smoking and total, distant metastatic, and fatal prostate cancer in 47,781 male health professionals throughout the United States followed with questionnaires. From 1986 to 1994, we documented 1369 men with prostate cancer (excluding stage A1). One hundred fifty-two of the men had distant metastatic disease at diagnosis, and 103 fatal cases occurred from 1986 to 1994. Early (before age 30), late (within recent 10 years), and lifetime cumulative smoking history were unrelated to risk of total prostate cancer. However, men who had smoked 15 or more pack-years of cigarettes within the preceding 10 years were at higher risk of distant metastatic prostate cancer [multivariate relative risk (RR), 1.81; 95% confidence interval (CI), 1.05-3.11; P (trend), 0.03] and fatal prostate cancer [RR, 2.06; CI, 1.08-3.90; P (trend), 0.02] relative to nonsmokers. Within 10 years after quitting, the excess risk among smokers is eliminated. The higher rate of fatal prostate cancer among smokers did not appear to result from confounding by diet or other lifestyle factors, different screening behavior between smokers and nonsmokers, or from other smoking-related comorbidities. Our results indicate that although smoking was unrelated to prostate cancer incidence, recent tobacco use had a substantial impact on the occurrence of fatal prostate cancer.

Risk factors for basal cell carcinoma of the skin in men: results from the health professionals follow-up study.

Abstract: The authors examined the relation of constitutional factors and sun exposure to risk of basal cell carcinoma of the skin (BCC) in a prospective cohort of 44,591 predominantly Caucasian US male health professionals, 40-75 years of age and free of cancer at enrollment in 1986. During 8 years of follow-up, 3,273 cases of self-reported BCC were documented. The following variables were each associated with an elevated risk of BCC: having red hair; green, hazel, or blue eyes; a tendency to sunburn; and north European ancestry. The lifetime number of blistering sunburns was also positively associated with BCC risk (p trend < 0.0001). Compared with men who as teenagers had been outside less than once a week, men who had been outside weekly (relative risk (RR) = 1.30; 95% confidence interval (CI): 1.14, 1.47) and daily (RR = 1.42; 95% CI: 1.24, 1.63) had an elevated risk of BCC. Living in a region of residence with high solar radiation as an adult was also associated with an increased risk of BCC (RR = 1.48; 95% CI: 1.36, 1.60), whereas living in such a region only in childhood did not increase BCC risk. These results confirm the role of constitutional factors and suggest that adult sun exposure increases BCC risk.

Alcohol Consumption, Cigarette Smoking, and Risk of Benign Prostatic Hyperplasia

Abstract: Alcohol consumption and cigarette smoking were evaluated in relation to development of benign prostatic hyperplasia (BPH) among 29,386 members of the Health Professionals Follow-up Study. Men who were 40-75 years old in 1986 and free of prior BPH surgery, diagnosed cancer at baseline, and prostate cancer at baseline and during follow-up were followed for incidence of BPH surgery from 1986 to 1994. Cases were men who reported BPH surgery between 1986 and 1994 (n = 1,813) or who scored > or = 15 points of 35 on seven lower urinary tract symptom questions modified from the American Urological Association symptom index in 1992 and 1994 (n = 1,786); noncases were men who scored or = 50.1 g/day vs. 0: OR = 0.72, 95% CI 0.57-0.90). Current cigarette smoking was positively related to total BPH only among those who smoked 35 or more cigarettes/day (compared with never smokers: OR = 1.45, 95% CI 1.07-1.97). These findings suggest that moderate alcohol consumption and avoidance of smoking may benefit BPH.

MTHFR Polymorphism, Methyl-Replete Diets and the Risk of Colorectal Carcinoma and Adenoma among U.S. Men and Women: An Example of Gene-Environment Interactions in Colorectal Tumorigenesis

Abstract: Our studies on interactions of a folate-metabolizing gene polymorphism and dietary intake in colorectal tumorigenesis demonstrate the potential importance of studying interactions between genotype and environmental exposure in relation to cancer risk. We observed an inverse association of a polymorphism (667C --> T, ala --> val) in the methylenetetrahydrofolate reductase (MTHFR) gene with colorectal cancer but not with colorectal adenomas. The inverse association of methionine and adverse association of alcohol with colorectal cancer were stronger among val/val individuals. These interactions were not present in studies of colorectal adenomas. Our studies illustrate that studying gene-environment interactions in relation to cancer can be of importance in clarifying cancer etiology as well as pointing to preventive dietary modifications.

Harvard Report on Cancer Prevention. Volume 3: prevention of colon cancer in the United States.

Abstract: Colon cancer is a preventable disease. We understand many aspects of its pathogenesis and the factors that in ̄uence its development. In addition, several e€ective screening tools exist for the early detection of colon cancer. However, to date, we have not e€ectively utilized existing knowledge to reduce the burden of colon cancer in the United States. Colon cancer is the third most common form of cancer among men and women in the United States [1]. When statistics for men and women are combined, colon cancer is second only to lung cancer as the leading cause of cancer mortality in the United States, accounting for 47,700 deaths each year [1]. In this article, we review the pathogenesis of this disease and the burden it presents to the United States. We then review modi®able risk factors for colon cancer and summarize the evidence for screening as a preventive measure. Finally, we discuss preventive strategies for reducing the burden of colon cancer in the United States. This article will focus exclusively on colon cancer, rather than colon and rectal cancers combined, since rectal cancers make up a small portion of overall cancers, the risk factors for colon and rectal cancers di€er, and the bene®ts of screening for rectal cancer alone are minimal.

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

Abstract: ContextCoffee has several metabolic effects that could reduce the risk of gallstone formation.ObjectiveTo examine the association between coffee consumption and the risk of symptomatic gallstone disease in men.Design and SettingThe Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996.ParticipantsA total of 46,008 men, aged 40 to 75 years in 1986, without history of gallstone disease.Main Outcome MeasuresNewly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy.ResultsDuring 404,166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend=.005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (≤25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk.ConclusionsIn this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men.

Abstract: African-American men have the highest and Asian-American men have the lowest prostate cancer incidence rates in the United States; internationally, rates for the Asian continent are among the lowest. Higher insulin-like growth factor (IGF)-1, which participates in the control of cellular growth and differentiation and is modulated by IGF-binding protein-3 (IGFBP-3), was associated with an increased prostate cancer risk in three recent studies. We, therefore, investigated whether plasma levels of IGF-1 and IGFBP-3 vary by race in United States men selected from among members of the Health Professionals Follow-up Study who were 47-78 years old in 1993-1995 when they provided blood (n = 18,000). All of the men who described their major ancestry as African American (n = 63) and a random sample of 75 Asians and 75 Caucasians were invited to provide a second blood sample in 1997, of whom 42, 52, and 55, respectively, did so. IGF-1 and IGFBP-3 concentrations were determined by ELISA. We used nonparametric methods to assess racial variation in age-adjusted levels. Caucasians had the highest median IGF-1 level (224 ng/ml), followed by Asians (208 ng/ml) and African Americans (205 ng/ml). Median IGFBP-3 concentration was similar between Caucasians and Asians but was more than 13% lower in African Americans. Median molar IGF-1:IGFBP-3 ratio was greatest in Caucasians and lowest in Asians. The lower IGF-1 blood levels relative to IGFBP-3 levels among Asian men are consistent with their lower prostate cancer incidence. Although differences in circulating IGF-1 do not seem to account for the greater prostate cancer risk among African-American men, their absolute lower levels of IGFBP-3 may be contributory.

The V89L Polymorphism in the 5α-Reductase Type 2 Gene and Risk of Prostate Cancer

Abstract: 5alpha-Reductase type 2, the predominant prostatic isozyme of this protein, converts testosterone to dihydrotestosterone. It has been hypothesized that individuals with greater 5alpha-reductase activity are at increased risk for prostate cancer (CaP). A single nucleotide polymorphism of the 5alpha-reductase type 2 gene (SRD5A2) gives rise to a substitution of leucine (leu) for valine (val) at codon 89 (V89L), the presence of which may affect serum androstanediol glucuronide (AAG) levels. We studied the effect of this polymorphism on the risk of prostate cancer in a prospective, nested, case-control design within the Physicians' Health Study. In all controls (n = 799), the leu allele frequency was 0.30. Among the 386 controls with plasma AAG levels available, there was no significant association between AAG levels and V89L genotype. We also detected no significant association between risk for CaP and genotype [odds ratio: val/val = 1.0 (reference), leu/val = 0.96 (95% confidence interval, 0.76-1.20), and leu/ leu = 0.84 (95% confidence interval, 0.57-1.24)]. These data do not support a moderate to large effect of the SRD5A2 V89L polymorphism on plasma AAG levels or CaP risk in this predominantly Caucasian cohort, although a small effect cannot be completely excluded.

Prospective study of alcohol consumption patterns in relation to symptomatic gallstone disease in men.

Abstract: Although the association between alcohol intake and gallstone disease has been characterized previously, the relation between alcohol consumption patterns, specific types of alcoholic beverages, and risk for cholelithiasis has not been addressed systematically. These issues were examined prospectively in a cohort of men who were free from symptomatic gallstone disease in 1986 and were followed to 1996. During follow-up, 2.4% of the men reported newly symptomatic gallstones that were diagnosed by ultrasonography or x-ray, or a cholecystectomy. After adjusting for other known or suspected risk factors, an increase in the amount of alcohol consumed was associated with a decreased risk of symptomatic gallstone disease. An increase in frequency of alcohol consumption also was related to decreased risk. Combining the reports of quantity and frequency of alcohol intake, a consumption pattern that reflected frequent intake (5-7 days/week) of any given amount of alcohol was associated with a decreased risk, as compared with nondrinkers. In contrast, infrequent alcohol intake (1-2 days/week) showed no significant association with risk. All alcoholic beverage types were inversely associated with risk of symptomatic gallstone disease, independent of patterns of consumption. These results suggest that frequent, moderate intake of alcohol decreases the risk for symptomatic gallstone disease, in contrast to infrequent or episodic alcohol intake. Recommendations regarding the benefit of moderate quantities of alcohol for gallstone disease should be weighed against the potential health hazards of alcohol consumption.

CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. physicians.

Abstract: BACKGROUND CAG repeat length in exon 1 of the androgen receptor (AR) gene correlates inversely with transcriptional transactivation activity of the AR. Men with shorter AR CAG repeat lengths are at higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that a shorter AR gene CAG repeat length increases the risk of developing of BPH. METHODS Among 14,916 men of the Physicians' Health Study who had provided a blood sample in 1982, we measured AR gene CAG repeat lengths for 310 men who had surgery for BPH up to 7.5 years of follow-up and 1,041 controls. RESULTS Risk of surgery for BPH increased linearly with decreasing AR CAG repeat length (P (trend) = 0.03). Relative to men with a CAG repeat length ⩾25, men with a repeat length ⩽19 had an odds ratio of BPH surgery of 1.76 (95% confidence interval, 1.16–2.65). CONCLUSIONS Variability in the AR gene CAG repeat influences the development of symptomatic BPH. Prostate 39:130–134, 1999. © 1999 Wiley-Liss, Inc.

Glycosylated hemoglobin and risk of colorectal cancer and adenoma (United States).

Abstract: Objectives: The consistently observed epidemiologic associations of obesity and physical activity with colorectal cancer and precursor adenoma risk suggest that insulin and glucose control may be contributory We evaluated the association of glycosylated hemoglobin (HbA1c), a clinical indicator of average glycemia over the previous 2 months, and possibly, indirectly, a marker of average blood insulin level, with colorectal carcinogenesis