PURPOSE: Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential... more
PURPOSE: Inflammation is a process central to carcinogenesis and in particular to colorectal cancer (CRC). Previously, we developed a dietary inflammatory index (DII) from extensive literature review to assess the inflammatory potential of diet. In the current study, we utilized this novel index in the Women's Health Initiative to prospectively evaluate its association with risk of CRC in postmenopausal women. METHODS: The DII was calculated from baseline food frequency questionnaires administered to 152,536 women aged 50-79 years without CRC at baseline between 1993 and 1998 and followed through 30 September 2010. Incident CRC cases were ascertained through a central physician adjudication process. Multiple covariate-adjusted Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence intervals (95 % CI) for colorectal, colon (proximal/distal locations), and rectal cancer risk, by DII quintiles (Q). RESULTS: During an average 11.3 yea...
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Consumption of foods with a high glycemic index (GI) or glycemic load (GL) is hypothesized to contribute to insulin resistance, which is associated with increased risk of diabetes mellitus, obesity, cardiovascular disease, and some... more
Consumption of foods with a high glycemic index (GI) or glycemic load (GL) is hypothesized to contribute to insulin resistance, which is associated with increased risk of diabetes mellitus, obesity, cardiovascular disease, and some cancers. However, dietary assessment of GI and GL is difficult because values are not included in standard food composition databases. Our objective was to develop a database of GI and GL values that could be integrated into an existing dietary database used for the analysis of FFQ. Food GI values were obtained from published human experimental studies or imputed from foods with a similar carbohydrate and fiber content. We then applied the values to the Women's Health Initiative (WHI) FFQ database and tested the output in a random sample of previously completed WHI FFQs. Of the 122 FFQ line items (disaggregated into 350 foods), 83% had sufficient carbohydrate (>5 g/serving) for receipt of GI and GL values. The foods on the FFQ food list with the hi...
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Although genome-wide association studies have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD), and colorectal cancer (CRC), there has been no large-scale examination for... more
Although genome-wide association studies have separately identified many genetic susceptibility loci for ulcerative colitis (UC), Crohn's disease (CD), and colorectal cancer (CRC), there has been no large-scale examination for pleiotropy, or shared genetic susceptibility, for these conditions. We used logistic regression modeling to examine the associations of 181 UC and CD susceptibility variants previously identified by GWAS with risk of CRC using data from the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We also examined associations of significant variants with clinical and molecular characteristics in a subset of the studies.Among 11,794 CRC cases and 14,190 controls, rs11676348, the susceptibility SNP for UC, was significantly associated with reduced risk of CRC (p = 7E-05). The multivariate-adjusted odds ratio of CRC with each copy of the T allele was 0.93 (95% CI, 0.89-0.96). The association of the SNP with risk of CRC d...
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High body mass index (BMI) is consistently linked to increased risk of colorectal cancer (CRC) for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we... more
High body mass index (BMI) is consistently linked to increased risk of colorectal cancer (CRC) for men, whereas the association is less clear for women. As risk estimates from observational studies may be biased and/or confounded, we conducted a Mendelian randomization study to estimate the causal association between BMI and CRC. We used data from 10,226 CRC cases and 10,286 controls of European ancestry. The Mendelian randomization analysis used a weighted genetic risk score, derived from 77 genome-wide association study identified variants associated with higher BMI, as an instrumental variable (IV). We compared the IV odds ratio (IV-OR) with the OR obtained using a conventional covariate-adjusted analysis. Individuals carrying greater numbers of BMI-increasing alleles had higher CRC risk (per weighted allele OR, 1.31; 95% confidence interval [CI], 1.10-1.57). Our IV estimation results support the hypothesis that genetically influenced BMI is directly associated with risk for CRC ...
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Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we... more
Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. Colorectal cancer. Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74];...
Research Interests: Humans, Female, Male, Risk factors, Aspirin, and 5 moreGenotype, Risk Factors, Genetic Markers, JAMA, and Case Control Studies
The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed... more
The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial designed to determine the effects of a high-fiber, high-fruit and vegetable, low-fat diet on the recurrence of adenomatous polyps in the large bowel. Detailed dietary intake and supplement use data were collected at baseline and at each of 4 annual study visits. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 y. Recurrence was found in 754 of the 1905 trial participants. We evaluated the association between calcium and vitamin D intake and adenomatous polyp recurrence after adjusting for intervention group, age, gender, nonsteroidal anti-inflammatory drug use, total energy intake, and the interaction of gender and intervention group. Vitamin D models were also adjusted for the location of the clinic site. Dietary variables were adjusted for total energy intake via the residual method. There were no overall significant associations between adenoma recurrence and dieta...
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We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women's Health Initiative (WHI). Although GWAS of glaucoma have been... more
We report a genome-wide association study (GWAS) and admixture analysis of glaucoma in 12 008 African-American and Hispanic women (age 50-79 years) from the Women's Health Initiative (WHI). Although GWAS of glaucoma have been conducted on several populations, this is the first to look at glaucoma in individuals of African-American and Hispanic race/ethnicity. Prevalent and incident glaucoma was determined by self-report from study questionnaires administered at baseline (1993-1998) and annually through 2005. For African Americans, there was a total of 658 prevalent cases, 1062 incident cases and 6067 individuals who never progressed to glaucoma. For our replication cohort, we used the WHI Hispanics, including 153 prevalent cases, 336 incident cases and 2685 non-cases. We found an association of African ancestry with glaucoma incidence in African Americans (hazards ratio 1.62, 95% CI 1.023-2.56, P = 0.038) and in Hispanics (hazards ratio 3.21, 95% CI 1.32-7.80, P = 0.011). Althou...
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Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088... more
Achieving long-term adherence to a dietary pattern is a challenge in many studies investigating the relationship between diet and disease. The Women's Healthy Eating and Living Study was a multi-institutional randomized trial in 3088 women at risk for breast cancer recurrence. At baseline, the average participant followed a healthy dietary pattern of 7 vegetable and fruit servings, 21 g/d of fiber, and 28.7% energy from fat, although fat intake increased over the enrollment period. Using primarily telephone counseling, the intervention group was encouraged to substantially increase intakes of vegetables, fruits, and fiber while decreasing fat intake. Sets of 24-h dietary recalls were completed on 90% of eligible participants at 1 y and 86% at 4 y. Using a conservative imputation analysis, at 1 y, the intervention group consumed 38% more vegetable servings (100% when including juice) than the comparison group, 20% more fruit, 38% more fiber, 50% more legumes, and 30% more whole g...
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The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. We investigated the association of specific comorbidities with mortality in a multiethnic cohort of... more
The role of comorbidities in survival of patients with breast cancer has not been well studied, particularly in non-white populations. We investigated the association of specific comorbidities with mortality in a multiethnic cohort of 8,952 breast cancer cases within the California Breast Cancer Survivorship Consortium (CBCSC), which pooled questionnaire and cancer registry data from five California-based studies. In total, 2,187 deaths (1,122 from breast cancer) were observed through December 31, 2010. Using multivariable Cox proportional hazards regression, we estimated HRs and 95% confidence intervals (CI) for overall and breast cancer-specific mortality associated with previous cancer, diabetes, high blood pressure (HBP), and myocardial infarction. Risk of breast cancer-specific mortality increased among breast cancer cases with a history of diabetes (HR, 1.48; 95% CI, 1.18-1.87) or myocardial infarction (HR, 1.94; 95% CI, 1.27-2.97). Risk patterns were similar across race/ethni...
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Risk factors for colon cancer may not only influence the overall risk of cancer but also the risk for specific types of mutations. We evaluated the effect of polymorphisms in four insulin-related genes (G972R in IRS1, G1057D in IRS2, a CA... more
Risk factors for colon cancer may not only influence the overall risk of cancer but also the risk for specific types of mutations. We evaluated the effect of polymorphisms in four insulin-related genes (G972R in IRS1, G1057D in IRS2, a CA repeat in IGFI and an A/C polymorphism at -202 of IGFBP3) on the risk of microsatellite instability and KRAS2 and TP53 mutations in a population-based set of 1788 cases of colon cancer and 1981 controls. The GR/RR IRS1 genotypes were associated with an increased risk of colon cancers with the KRAS2 G12D mutation (OR 2.3, 95% CI 1.5, 3.5 versus controls, OR 1.7, 95% CI 1.1, 2.6 versus KRAS2 wild type), the "no 192" IGFI genotype increased the risk of the KRAS2 G13D mutation (OR 2.3, 95% CI 1.2, 4.2 versus controls, OR 2.1, 95% CI 1.1, 4.0 versus wild type), and the DD IRS2 genotype increased the risk of the G12V KRAS2 mutation (OR 1.8, 95% CI 0.9, 3.5 versus controls, OR 2.0, 95% CI 1.0, 4.0 versus wild type). Polymorphisms in IRS1 and IGF1 were also associated with an approximately two-fold increased risk of specific TP53 mutations relative to controls without cancer. We conclude that polymorphisms in some insulin-related genes are associated with an increased risk of colon cancer with specific KRAS2 and TP53 mutations, implying a link between these genetic changes and specific mutational pathways in carcinogenesis.
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This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind,... more
This study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes. A double-blind, placebo-controlled, randomized trial of low-dose oral 17β-E2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical placebo, was conducted among 339 women (aged 40-62 y) experiencing two or more vasomotor symptoms (VMS) per day (mean [SD], 8.07 [5.29]) who were recruited at three clinical sites from November 2011 to October 2012. The primary trial outcome, as reported previously, was frequency of VMS at 8 weeks. Here, we report on secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and from measures of pain (Pain, Enjoyment in life, and General activity scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and perceived stress (Perceived Str...
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Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene-environment interaction involving the... more
Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer. Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. Data on 9,160 cases and 9,280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, postmenopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red mea...
Research Interests: Diet, Humans, Female, Male, Young Adult, and 7 moreRisk factors, Aged, Middle Aged, Genotype, Adult, Risk Factors, and Case Control Studies
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Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is... more
Estrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date. To determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS). In total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012. Participants were randomized to double-blind treatment wi...
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The Women's Health Initiative (WHI) low-fat (20% kcal) dietary modification (DM) trial (1993-2005) demonstrated a nonsignificant reduction in breast cancer, a nominally significant reduction in ovarian cancer, and no effect on other... more
The Women's Health Initiative (WHI) low-fat (20% kcal) dietary modification (DM) trial (1993-2005) demonstrated a nonsignificant reduction in breast cancer, a nominally significant reduction in ovarian cancer, and no effect on other cancers (mean 8.3 years intervention). Consent to nonintervention follow-up was 83% (n = 37,858). This analysis was designed to assess postintervention cancer risk in women randomized to the low-fat diet (40%) versus usual diet comparison (60%). Randomized, controlled low-fat diet intervention for prevention of breast and colorectal cancers conducted in 48,835 postmenopausal U.S. women, ages 50 to 79 years at 40 U.S. sites. Outcomes included total invasive cancer, breast cancer, and colorectal cancer, and cancer-specific and overall mortality. There were no intervention effects on invasive breast or colorectal cancer, other cancers, or cancer-specific or overall mortality during the postintervention period or the combined intervention and follow-up p...
Research Interests: Humans, Female, Incidence, Risk factors, Aged, and 4 moreMiddle Aged, Food habits, Neoplasms, and Risk Factors
The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Using data from an incident population-based... more
The association between body mass index (BMI) and colon cancer has been reported to be different for men and women. No prior literature has examined if estrogen influences these differences. Using data from an incident population-based case (n = 1,972) and control (n = 2386) study of colon cancer we evaluated if estrogen modifies the association between BMI and risk of colon cancer. Women who were estrogen-negative (postmenopausal women not taking hormone replacement therapy, HRT) were at increased risk of colon cancer regardless of indicator of estrogen status used (i.e. estrogen-negative compared to estrogen-positive women defined as either being premenopausal or postmenopausal women using HRT, OR 1.54, 95% CI 1.23-1.93; no recent exposure to estrogens compared to current or HRT use within the past 2 years, OR 1.58, 95% CI 1.24-2.00; postmenopausal women not currently using HRT compared to postmenopausal women taking HRT, OR 1.65, 95% CI 1.29-2.12). BMI (kg/m2) was not associated ...
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Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is... more
Red meat intake has been associated with risk of colorectal cancer, potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and colorectal cancer has been inconsistently reported. We used pooled individual-level data from the Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. From 11 studies, 8,290 colorectal cancer cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of colorectal cancer compared with the lowest quartile [OR, 1.41; 95% confidence interval (CI), 1.29-1.55]. However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with colorectal cancer in those with a rapid/intermediate NAT2 genotype (OR, 1.38; 95% CI, 1.20-1.59) as with a slow genotype (OR, 1.43; 95% CI, 1.28-1.61; P interaction = 0.9). We found that high red meat intake was associated with increased risk of colorectal cancer only from retrospective case-control studies and not modified by NAT2 enzyme activity. Our results suggest no interaction between NAT2 genotype and red meat intake in mediating risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(1); 198-205. ©2014 AACR.
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Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD;... more
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer than the general population. Genome-wide association studies have identified and replicated several loci associated with risk of IBD; however, it is currently unknown whether these loci are also associated with colon cancer risk. We selected 15 validated SNPs associated with risk of either Crohn's disease, ulcerative colitis, or both in previous GWAS and tested whether these loci were also associated with colon cancer risk in a two-stage study design. We found that rs744166 in STAT3 was associated with colon cancer risk in two studies; however, the direction of the observation was reversed in TP53 mutant tumors possibly due to a nullification of the effect by mutant p53. The SNP, which lies within intron 1 of the STAT3 gene, was associated with lower expression of STAT3 mRNA in TP53 wild-type, but not mutant, tumors. These data suggest that the STAT3 locus is associated with both IBD and cancer. Further understanding the function of this variant in relation to TP53 could possibly explain the role of this gene in autoimmunity and cancer. Furthermore, an analysis of this locus, specifically in a population with IBD, could help to resolve the relationship between this SNP and cancer.
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Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal... more
Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention.
Research Interests: Genetics, Risk, Diet, Humans, Female, and 14 moreMeat, Male, Young Adult, Fruit, Risk factors, Vegetables, Aged, Middle Aged, Genotype, Adult, Dietary fiber, PLoS Genetics, Risk Factors, and Case Control Studies
Research Interests: Nutrition and Dietetics, Nutrition, Carotenoids, Ovarian Cancer, Antioxidants, and 14 moreVitamin A, Postmenopausal Women, Prospective studies, Case Report, Humans, Cox Regression, vitamin C, Female, Food Frequency Questionnaire, Aged, Middle Aged, Nutrition and Cancer, Ascorbic Acid, and Prospective Study
Lack of energy balance, or greater energy intake than expenditure as indicated by a large body mass index (BMI), has been associated with colon cancer, although less is known about its association with rectal cancer. In this study, we... more
Lack of energy balance, or greater energy intake than expenditure as indicated by a large body mass index (BMI), has been associated with colon cancer, although less is known about its association with rectal cancer. In this study, we examined the association between BMI, energy intake, and energy expenditure and their combined effect on rectal cancer risk. A population-based case-control study was conducted in Utah and Northern California. Incident cases (n = 952) of rectal cancer and population-based controls (n = 1205) were interviewed between 1997 and 2002 to obtain detailed information on body size, dietary intake, and physical activity patterns. BMI (kg/m(2)) was not associated with rectal cancer in either men or women. Participation in vigorous leisure-time physical activity over the past 20 yr was associated with a significant 40% reduction in rectal cancer risk. Energy intake was associated significantly with increased risk of rectal cancer, especially among people whose diagnosis was prior to age 60 yr (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.7-9.1 for men; OR = 2.8; 95% CI = 1.1-7.2 for women). There was a significant interaction between energy intake and energy expenditure, although not between BMI and either energy intake or energy expenditure. These data suggest that large BMI, an indicator of lack of energy balance, is not an important component of the etiology of rectal cancer. However, both physical activity and energy intake were significantly associated with rectal cancer risk. These data suggest that energy expenditure and energy intake alter rectal cancer risk through mechanisms other than energy balance.
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Eating frequency has been found in most previous studies to have a positive association or no association with colon cancer. We report data from a large case-control study to determine the effect of eating frequency on colon cancer risk.... more
Eating frequency has been found in most previous studies to have a positive association or no association with colon cancer. We report data from a large case-control study to determine the effect of eating frequency on colon cancer risk. Data were analyzed from interviews of 1,966 cases of colon cancer and 2,380 controls from selected areas in Northern California, Utah, and Minnesota. Respondents were asked whether they usually ate or drank something besides water at eight different occasions during the day. We controlled for age, family history of colorectal cancer, body mass index, physical activity, intake of non-steroidal anti-inflammatory medication, and dietary intake of energy, fiber, and calcium. In fully adjusted models, we found no significant associations between number of daily eating occasions and colon cancer in women. In men, risk of overall colon cancer was lower for one to two times per day (odds ratio = 0.54, 95% confidence interval = 0.36-0.83) than for three times per day, but risk was not increased for more than three times per day. Compared with three times per day, we found no evidence for an association between colon cancer risk and eating frequencies more than three times per day. The increased risk of colon cancer limited to men eating less than three times per day may be due to uncontrolled confounding.
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Research Interests: Depression, Yoga, Treatment Outcome, Menopause, Anxiety, and 7 moreMeditation, Humans, Female, Exercise, Middle Aged, ANXIETY, and Hot Flashes
To describe methods used to computerize the diet history questionnaire developed for the Coronary Artery Risk Factor Development in Young Adult (CARDIA) study and to describe quality-control procedures used in conjunction with dietary... more
To describe methods used to computerize the diet history questionnaire developed for the Coronary Artery Risk Factor Development in Young Adult (CARDIA) study and to describe quality-control procedures used in conjunction with dietary assessment. The computerized diet history is being used in a case-control study. Because of the computerized nature of the questionnaire, we developed quality-control procedures that incorporate listening to an audiotape of the interview while visually reviewing recorded data. Three centers involved in a population-based epidemiologic study of colon cancer. Men and women between the ages of 30 and 79 years. Quality-control results showed that 100% of the computerized forms would be free of errors if the data were subjected to visual review only. Probing errors, which accounted for 47.3% of all errors, were the most commonly encountered errors. In probing errors the interviewer did not probe in a nondirective manner, or the interviewer failed to verify responses that might be considered questionable. The CARDIA diet history was computerized for use in epidemiologic studies of the association between diet and disease. Review of the audiotapes of the interviews showed that most errors made in obtaining a dietary assessment were not detectable from visual review of the data. Although the quality-control procedures were developed for a computerized diet history questionnaire, they are applicable to other dietary assessment methods.
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To examine the relationship of dietary change to weight change in women who quit smoking and remained abstinent for 1 year. For 1 year, 582 women participating in smoking cessation classes were studied. Weight, diet, and physical activity... more
To examine the relationship of dietary change to weight change in women who quit smoking and remained abstinent for 1 year. For 1 year, 582 women participating in smoking cessation classes were studied. Weight, diet, and physical activity were measured at baseline and at 1, 6, and 12 months after smoking cessation. Multivariate regression models were used to predict 1-year weight change for the 139 women who remained abstinent. Women gained, on average, 9.9 lb over a 1-year period while increasing their intake of energy for 1 and 6 months but returning to baseline levels by 1 year. Sucrose, total carbohydrate, and fat intake increased significantly for the first month; fat and total carbohydrate intake remained at an increased level for 6 months. In unadjusted analyses, older women and those who smoked more cigarettes gained more weight than younger women and lighter smokers; lighter and heavier women gained more weight than women of intermediate weight. In adjusted analyses, age remained a significant factor and number of cigarettes remained of borderline significance. Change in energy intake was predictive of weight change only in women with the highest energy intake at baseline. Dietitians should acknowledge that most women who quit smoking gain weight in the short term. Although many women increase their energy intake, change in energy level is only one factor in weight change. Over the long term, women with high baseline intakes appear to be able to affect their weight change by reducing their energy intake.
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To determine if dietary antioxidants play a role in preventing coronary heart disease (CHD) by having an impact on lipid levels. Data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to assess the... more
To determine if dietary antioxidants play a role in preventing coronary heart disease (CHD) by having an impact on lipid levels. Data from the Coronary Artery Risk Development in Young Adults (CARDIA) Study were used to assess the associations of reported intake of vitamins A, C, E and beta carotene, and their use in supplements, with lipid levels in a black and white, healthy adult (18 to 30 years of age at the baseline examination) population. After adjusting for age, education level, physical activity, body size, alcohol consumption and caloric intake, vitamin A, beta carotene, and vitamin C (white women) intake were directly associated with HDL-cholesterol levels among women who smoked cigarettes, with the strongest associations being observed for white women. Black men who took supplements of vitamins A and C and did not smoke cigarettes had significantly higher HDL-cholesterol levels compared to those in the lowest levels of dietary intake. Although vitamin E was associated with higher levels of HDL-cholesterol, the association was only of borderline significance among white men who smoked cigarettes (p = 0.06). We did not observe any consistent associations between antioxidants and other plasma lipids, including total cholesterol, LDL-cholesterol, or triglycerides. We conclude that dietary antioxidants are associated with HDL-cholesterol levels in some subsets of the population, although these associations may be operating in conjunction with other lifestyle behaviors.
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Research Interests: Risk assessment, Ovarian Cancer, Postmenopausal Women, Humans, Weight Loss, and 24 moreUnited States, Female, Follow-up studies, Fruit, The, Incidence, Cereals, Risk factors, Vegetables, Group Intervention, Aged, Middle Aged, Food habits, Neoplasm Invasiveness, Randomized Controlled Trial, Odds ratio, Dietary pattern, Neoplasms, Cancer Incidence, Risk Factors, Risk Assessment, Proportional Hazards Models, Confidence Interval, and Control Group
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Research Interests: Breast Cancer, Risk assessment, Cardiovascular disease, Colorectal cancer, Postmenopausal Women, and 25 moreStroke, Humans, Chronic Disease, United States, Female, Pulmonary Embolism, Disease Prevention, Hip Fractures, Hysterectomy, Aged, Middle Aged, Estrogens, Coronary heart disease, Risk Reduction, Randomized Controlled Trial, Hip fracture, Hormone Therapy, Risk Assessment, Family Planning and Reproductive Health, Indexation, Proportional Hazards Models, National Institute of Health, JAMA, Confidence Interval, and Breast neoplasm
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Research Interests: Polymorphism, Cancer, Survival Analysis, Humans, Female, and 6 moreMale, Aged, Middle Aged, Adult, Colon cancer, and Case Control Studies
Although diet and its constituents have been studied extensively as risk factors for colon cancer, much less is known about how specific types of fluid influence colon cancer risk. In this study, we explored associations between colon... more
Although diet and its constituents have been studied extensively as risk factors for colon cancer, much less is known about how specific types of fluid influence colon cancer risk. In this study, we explored associations between colon cancer and total fluids, water and methylxanthine-containing beverages such as coffee, tea and cola; data were obtained from 1,993 incident cases of colon cancer and 2,410 population-based controls living in California, Utah and Minnesota. Our primary objective was to determine the influence on associations of amount consumed, confounding and effect modification. We observed few important differences between colon cancer and fluid consumption for all subjects combined. Among men, low levels of coffee intake were associated with an increased risk of colon cancer relative to non-consumers of coffee (OR 1.32, 95% CI 1.02-1.67), while at high levels of consumption, an inverse association was observed (OR 0.81, 95% CI 0.58-1.12). The observed associations were only slightly influenced by consumption of water or other potential confounding factors, but changing the referent group to those consuming one cup of coffee per day or less resulted in a stronger association and a more significant inverse linear trend (OR 0.71, 95% CI 0.53-0.96). The associations with coffee and caffeine- and methylxanthine-containing beverages were strongest for proximal tumors in men. High levels of water intake, however, were protective for distal tumors (OR for men 0.68, 95% CI 0.49-0.96). Assessment of the impact of smoking on associations between colon cancer and coffee showed a significant interaction between smoking and coffee for both men and women.
Research Interests: Cancer, Humans, Caffeine, Female, Male, and 7 moreRisk factors, Aged, Middle Aged, Beverages, Adult, Colon cancer, and Risk Factors
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A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully... more
A sizable fraction of colorectal cancer (CRC) is expected to be explained by heritable factors, with heritability estimates ranging from 12 to 35% twin and family studies. Genome-wide association studies (GWAS) have successfully identified a number of common single-nucleotide polymorphisms (SNPs) associated with CRC risk. Although it has been shown that these CRC susceptibility SNPs only explain a small proportion of the genetic risk, it is not clear how much of the heritability these SNPs explain and how much is left to be detected by other, yet to be identified, common SNPs. Therefore, we estimated the heritability of CRC under different scenarios using Genome-Wide Complex Trait Analysis in the Genetics and Epidemiology of Colorectal Cancer Consortium including 8025 cases and 10 814 controls. We estimated that the heritability explained by known common CRC SNPs identified in GWAS was 0.65% (95% CI:0.3-1%; P = 1.11 × 10-16), whereas the heritability explained by all common SNPs was at least 7.42% (95% CI: 4.71-10.12%; P = 8.13 × 10(-8)), suggesting that many common variants associated with CRC risk remain to be detected. Comparing the heritability explained by the common variants with that from twin and family studies, a fraction of the heritability may be explained by other genetic variants, such as rare variants. In addition, our analysis showed that the gene × smoking interaction explained a significant proportion of the CRC variance (P = 1.26 × 10(-2)). In summary, our results suggest that known CRC SNPs only explain a small proportion of the heritability and more common SNPs have yet to be identified.
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Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and... more
Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replicati...
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A randomized dietary intervention trial across 4 years examined diet, weight, and obesity incidence (body mass index [BMI]... more
A randomized dietary intervention trial across 4 years examined diet, weight, and obesity incidence (body mass index [BMI] > or = 30 kg/m(2)) differences between study groups. Participants were 1,510 breast cancer survivors with BMI > or = 25 kg/m(2) at entry. Dietary intake was assessed yearly by telephone; weight and height were measured at clinic visits. Intervention participants consumed more fruit, vegetables, and fiber and less energy from fat than control participants during follow-up cross-sectionally (p < .0001) and longitudinally (p < .0001); weight did not differ between study groups at any follow-up visit, and significant weight change difference was observed between groups only in the 1st year (p < .0001). Diet and weight results remained unchanged after stratifying by age and BMI. No difference in obesity incidence was found during follow-up (p > .10) among overweight members of either study group. Without specific efforts to reduce total energy intake, dietary modification does not reduce obesity or result in long-term weight loss.
Research Interests:
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting... more
Genome-wide association studies have identified a large number of single nucleotide polymorphisms (SNPs) associated with a wide array of cancer sites. Several of these variants demonstrate associations with multiple cancers, suggesting pleiotropic effects and shared biological mechanisms across some cancers. We hypothesised that SNPs previously associated with other cancers may additionally be associated with colorectal cancer. In a large-scale study, we examined 171 SNPs previously associated with 18 different cancers for their associations with colorectal cancer. We examined 13 338 colorectal cancer cases and 40 967 controls from three consortia: Population Architecture using Genomics and Epidemiology (PAGE), Genetic Epidemiology of Colorectal Cancer (GECCO), and the Colon Cancer Family Registry (CCFR). Study-specific logistic regression results, adjusted for age, sex, principal components of genetic ancestry, and/or study specific factors (as relevant) were combined using fixed-effect meta-analyses to evaluate the association between each SNP and colorectal cancer risk. A Bonferroni-corrected p value of 2.92×10(-4) was used to determine statistical significance of the associations. Two correlated SNPs--rs10090154 and rs4242382--in Region 1 of chromosome 8q24, a prostate cancer susceptibility region, demonstrated statistically significant associations with colorectal cancer risk. The most significant association was observed with rs4242382 (meta-analysis OR=1.12; 95% CI 1.07 to 1.18; p=1.74×10(-5)), which also demonstrated similar associations across racial/ethnic populations and anatomical sub-sites. This is the first study to clearly demonstrate Region 1 of chromosome 8q24 as a susceptibility locus for colorectal cancer; thus, adding colorectal cancer to the list of cancer sites linked to this particular multicancer risk region at 8q24.