Biomedical subjects

R W Haile

Publications and source records attributed to R W Haile.

At least 37 records · Page 2Linked to original sources

PubMed1998

Obesity, weight gain, large weight changes, and adenomatous polyps of the left colon and rectum.

Epidemiologic studies of colorectal neoplasia have usually examined body mass index as a risk factor, but not other aspects of obesity. During 1991-1993, the authors obtained weight histories and comprehensive covariate data from men and women aged 50-75 years who underwent sigmoidoscopy at a health maintenance organization in southern California. Using 483 cases with adenomas and 483 controls, measures of obesity (body mass index), positive energy balance (net weight gain in the past 10 years), and weight variability (large weight changes) were each independently related to adenoma prevalence. Compared with subjects in the lowest quartile of body mass index, multivariate-adjusted odds ratios for subjects in increasingly higher quartiles were 2.1 (95% confidence interval (CI) 1.4-2.3), 1.8 (1.1-2.9), and 1.7 (1.0-2.8), respectively. Compared with subjects who reported a net weight loss during the 10 years before sigmoidoscopy, subjects with net weight gains of 1.5-4.5 kg or > or = 4.5 kg had adjusted odds ratios (95% CI) of 2.5 (1.2-5.6) and 1.8 (0.7-4.4), respectively. Compared with subjects who had no large weight changes during adulthood, subjects with 1-2, 3, or > or = 4 changes had adjusted odds ratios (95% CI) of 2.0 (1.0-3.9), 2.5 (1.2-5.5), and 1.5 (0.6-3.6), respectively. Obesity, weight gain, and unstable adult weight may be independently associated with colorectal carcinogenesis.

Adenomatous Polyps↗

PubMed1998

Plasma tocopherol and prevalence of colorectal adenomas in a multiethnic population.

Although vitamin E can block mutagenesis and cell transformation in vitro and can reduce the number of chemically induced colonic adenomas in mice, previous clinical trials have found no protective effect of vitamin E supplements against colorectal adenomas, and epidemiological studies have found only weak protective effects of dietary or plasma alpha-tocopherol against colorectal cancer. We previously examined first diagnosis of colorectal adenomas in a sigmoidoscopy screening population and failed to find a protective effect of dietary vitamin E. Because measurements of dietary intake may not be a good proxy of vitamin E status, we assayed plasma alpha- and gamma-tocopherol concentration for 332 subjects with colorectal adenomas and 363 control subjects from this previous sigmoidoscopy-based study. Increasing alpha-tocopherol and decreasing gamma-tocopherol levels were associated with decreased occurrence of large (> or = 1 cm) but not of small (<1 cm) adenomas; however, after adjustment for potential confounding variables, these trends were not statistically significant. A strong trend (P = 0.02) was observed by using the alpha-tocopherol:gamma-tocopherol ratio, which may be a more sensitive indicator of alpha-tocopherol intake. Subjects in the highest versus lowest quintile of alpha-tocopherol: gamma-tocopherol ratio had an odds ratio of 0.36 (95% confidence interval, 0.14-0.95) for large adenomas. The finding that a high alpha-tocopherol:gamma-tocopherol ratio is associated with decreased occurrence of large, but not of small, colorectal adenomas is consistent with previous findings that alpha-tocopherol may be protective against colon cancer. A high plasma alpha-tocopherol:gamma-tocopherol ratio may be a better predictor of decreased cancer risk than high plasma alpha-tocopherol alone.

Adenoma↗

PubMed1998

Folate intake, alcohol consumption, cigarette smoking, and risk of colorectal adenomas.

BACKGROUND: Recent evidence suggests that folic acid (and derivatives) could contribute to the protective effect of fruits and vegetables against the risk of large-bowel cancer. Other evidence indicates that alcohol drinking and cigarette smoking may impair the biologic actions of folate. We used data from an adenoma prevention trial to investigate the occurrence of colorectal adenomas (possible precursors of colorectal cancer) in association with folate intake, alcohol consumption, and cigarette smoking. METHODS: Patients with at least one recent large-bowel adenoma were followed with colonoscopy 1 year and 4 years after their qualifying colon examinations. Adenomas detected after the year 1 examination were used as end points. A food-frequency questionnaire was administered at study entry and at study completion; nutrient intake at study entry was used in this analysis. All statistical tests were two-sided. RESULTS: After adjustment for caloric intake, dietary folate had a significant protective association with the risk of recurrence of large-bowel adenoma (P for trend = .04). However, this inverse association was attenuated by further adjustment for intake of dietary fiber and fat. Use of folate supplements was not associated with a reduction in risk. Alcohol intake (seven or more drinks/week) was associated with increased risk (odds ratio = 2.04; 95% confidence interval = 1.28-3.26). Cigarette smoking, even smoking for long duration, was not related to adenoma recurrence. CONCLUSIONS: These data provide only modest support for previous findings suggesting beneficial effects of folate on colorectal adenoma risk. We find no evidence that cigarette smoking increases risk. These findings do suggest a substantial increase in risk with alcohol consumption.

Adenoma↗

PubMed1998

Variants of N-acetyltransferase NAT1 and a case-control study of colorectal adenomas.

N-acetyltransferase NAT1, together with enzymes CYP1A2 and NAT2, helps convert heterocyclic amines to mutagens. Epidemiologic studies of the association of variants of these enzymes with colorectal cancer may provide indirect support for a heterocyclic amine mechanism. We used single strand conformation polymorphism and heteroduplex analysis to screen fro mutations in the NAT1 coding region in a case-control study (n = 932) of colorectal adenomas, which are precursors to cancer. Thirteen different single-base mutations were found: C97T, C190T, T402C, G445A-G459A-T640G ( a combination of three mutations), C559T, G560A, A613G, A752T, T777C, G781A, and A787G. Function of novel mutations was tested by bacterial production of enzymes and measurements of Km, Vmax, and stability. However, on 24-control individuals and 18 cases carried an inactivating NAT1 mutation. When combined with our data on the NAT2 acetylation polymorphism, we saw no evidence for an association between N-acetyltransferases and prevalence of adenomas. Larger sample sizes are required for further evaluation.

Acetyltransferases↗

PubMed1998

Recent use of hormone replacement therapy and the prevalence of colorectal adenomas.

The etiological role of hormone replacement therapy (HRT) (including estrogen only, combined estrogen-progesterone, and progesterone only) in colorectal neoplasia remains unclear. Several large studies have reported a reduced risk of colorectal cancer among HRT users; however, other studies have given inconsistent results. We examined the association between HRT and colorectal adenomatous polyps, precursors of colorectal cancer, among female participants in a case-control study. Subjects were members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy in 1991-1993. Participants received an in-person interview and completed a food frequency questionnaire. A total of 187 histologically confirmed cases and 188 controls, ages 50-75 years, were included in the analysis. Compared with women who did not use HRT during the year before sigmoidoscopy, recent users had an adjusted odds ratio of 0.57 (95% confidence interval, 0.35-0.94). Duration of use was inversely related to the prevalence of colorectal adenomas, with a multivariate-adjusted odds ratio of 0.49 (95% confidence interval, 0.25-0.97) for use of 5 years or more. These results support a protective effect of HRT on colorectal adenomatous polyps.

Adenomatous Polyps↗

PubMed1998

Dietary and supplemental calcium and the recurrence of colorectal adenomas.

The association between calcium intake and the risk of colorectal neoplasia remains controversial. This analysis prospectively investigated the association between dietary and supplemental calcium intake and recurrent colorectal adenomas. Participants were part of a multicenter, randomized clinical trial of antioxidant vitamins. The study endpoints were adenomas detected between surveillance colonoscopies conducted at approximately 1 year and 4 years after study entry. Baseline intake of energy-adjusted calcium derived from a food frequency questionnaire was used as the main exposure of interest. Calcium supplement use was assessed by semiannual questionnaires. Logistic regression was used to compute odds ratios and 95% confidence limits, and Poisson regression was used to estimate rate ratios. Subjects in the fifth quintile of dietary calcium had an adjusted odds ratio of 0.72 (95% confidence interval, 0.43-1.22) compared to those in the lowest quintile. Investigation of the numbers of adenomas yielded stronger findings: the rate ratio for the fifth quintile versus the first was 0.63 (95% confidence interval, 0.39-1.02). Dietary calcium seemed to have a greater effect among individuals with a high-fat diet than among those with a low-fat diet; however, the interaction was not statistically significant. Use of calcium supplements was not related to adenoma recurrence. These results suggest that a high calcium intake may be associated with a reduction in risk of recurrent adenomas, especially among individuals on a high-fat diet.

Adenoma↗

PubMed1998

Glutathione transferase null genotype, broccoli, and lower prevalence of colorectal adenomas.

Cruciferous vegetables, especially broccoli, may prevent cancer through anticarcinogenic compounds. For example, broccoli contains isothiocyanates that induce carcinogen-detoxifying enzymes. Glutathione transferase enzymes conjugate isothiocyanates, leading to excretion. We hypothesized that broccoli consumption in combination with the glutathione transferase M1 (GSTM1) null genotype would be associated with a lower prevalence of colorectal adenomas because of higher isothiocyanate levels. We used a case-control study of mainly asymptomatic subjects aged 50-74 years who underwent a screening sigmoidoscopy at either of two Southern California Kaiser Permanente Medical Centers during 1991-1993. Cases (n = 459) had a first-time diagnosis of histologically confirmed adenomas detected by flexible sigmoidoscopy. Controls (n = 507) had no polyp detected. Subjects had a 45-min in-person interview for information on various risk factors and basic demographic data and completed a 126-item, semiquantitative food frequency questionnaire. Blood samples were used for GSTM1 genotyping. Subjects with the highest quartile of broccoli intake (an average of 3.7 servings per week) had an odds ratio of 0.47 (95% confidence interval, 0.30-0.73) for colorectal adenomas, compared with subjects who reportedly never ate broccoli. When stratified by GSTM1 genotype, a protective effect of broccoli was observed only among subjects with the GSTM1 null genotype (P for trend, 0.001; P for interaction, 0.01). The observed broccoli-GSTM1 interaction is compatible with an isothiocyanate mechanism.

Adenoma↗

PubMed1997

A sigmoidoscopy-based case-control study of polyps: macronutrients, fiber and meat consumption.

We conducted a large, sigmoidoscopy-based case-control study to examine the relation of intake of macronutrients, meat, and fiber to occurrence of adenomas of the large bowel. Cases were subjects diagnosed for the first time with one or more histologically confirmed adenomas. Controls had no polyps of any type at sigmoidoscopy, had no history of polyps, and were individually matched to cases by gender, age, date of sigmoidoscopy, and Kaiser Center. The response rate was 84% for cases and 82% for controls. Complete dietary data for 488 matched pairs were available. All odds ratios are from matched analyses adjusted for energy. We observed positive associations with risk of adenomas for calories, animal fat, saturated fat, red meat, and the ratio of red meat to poultry and fish. Protective effects were observed for vegetable protein, carbohydrates, and dietary fiber. The fiber effects diminished after adjusting for fruits and vegetables. Results after mutually adjusting for the effects of saturated fat, fiber and the ratio of red meat to chicken and fish suggest that each of these variables has an effect on risk of adenomas that is independent of the other 2 exposures.

Aged↗

PubMed1997

Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women?

We conducted a study to determine whether the risk of breast cancer associated with oral contraceptive (OC) use is higher in women with BRCA1/BRCA2 mutations than in other women by examining whether breast cancer patients with these mutations were more likely than breast cancer patients without mutations in BRCA1/BRCA2 to have used OCs. We tested for BRCA1 185delAG and 5382insC and BRCA2 6174delT mutations in a population-based sample of 50 young Ashkenazi Jewish breast cancer patients. Nine patients (18%) had a BRCA1 mutation, and five patients (10%) had a BRCA2 mutation. Long-term OC use (>48 months) before a first full-term pregnancy was associated with an elevated risk of being classified as a mutBRCA carrier (odds ratio, 7.8; trend, P = 0.004). The results suggest that OC use may increase the risk of breast cancer more in mutBRCA carriers than in noncarriers; however, they must be interpreted with caution given the small sample size.

Adult↗

PubMed1997

Plasma carotenoids and the prevalence of adenomatous polyps of the distal colon and rectum.

In a case-control study, the authors investigated relations between plasma carotenoid concentrations and the prevalence of colorectal adenomatous polyps (precursors to colorectal cancer) in residents of Los Angeles County and Orange County, California, from 1991 through 1993. Plasma concentrations of six carotenoids were compared in 472 asymptomatic cases with a first-time diagnosis of at least one adenomatous polyp of the distal colon or rectum and 502 matched controls. Odds ratios adjusted for age, sex, smoking, alcohol intake, and energy, saturated fat, and fruit and vegetable intake revealed no associations between any of the individual carotenoids and polyp prevalence or between total carotenoids and polyp prevalence.

Adenomatous Polyps↗

PubMed1997

Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor.

BACKGROUND: Prostate cancer is an increasingly common disease for which there are few well-established risk factors. Family history data suggest a genetic component; however, the majority of prostate cancer cases cannot be explained by a single-gene model. Prostate cell division is influenced by two steroid hormones, testosterone and vitamin D, the action of each being mediated by its respective receptor. The genes for the two receptors are candidates in a multigenic model for prostate cancer susceptibility. PURPOSE: We examined genetic polymorphisms in two steroid receptors, the androgen receptor (AR) and the vitamin D receptor (VDR), in a case-control pilot study of prostate cancer. METHODS: Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene. To compare genotypes with respect to prostate cancer risk, we estimated odds ratios (ORs) by using logistic regression. ORs were also estimated separately for advanced and localized cases of disease. All P values resulted from two-sided tests. RESULTS: Both the AR and the VDR polymorphisms were associated, individually and after mutual adjustment, with prostate cancer. Adjusted ORs (95% confidence intervals [CIs]) for prostate cancer were 2.10 (95% CI = 1.11-3.99) for individuals carrying an AR CAG allele with fewer than 20 repeats versus an allele with 20 or more repeats and 4.61 (95% CI = 1.34-15.82) for individuals carrying at least one long (A18 to A22) VDR poly-A allele versus two short (A14 to A17) poly-A alleles. For both the AR and VDR genes, the at-risk genotypes were more strongly associated with advanced disease than with localized disease. CONCLUSIONS: In this pilot study, genetic variation in both the VDR and the AR genes was associated with prostate cancer, and both genes appear to preferentially confer risk for advanced disease. These two genetic risk factors, if confirmed, are among the strongest risk factors yet identified for prostate cancer. IMPLICATIONS: These results are consistent with a multigenic model of prostate cancer susceptibility. On the basis of the joint effect of several genetic loci, one might ultimately be able to construct a risk profile to predict advanced disease, so that men whose disease is unlikely to progress to an advanced stage can possibly be spared aggressive treatment.

Alleles↗

PubMed1997

Diet and premenopausal bilateral breast cancer: a case-control study.

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.

Adult↗

PubMed1997

Meat preparation and colorectal adenomas in a large sigmoidoscopy-based case-control study in California (United States).

The often observed association between red meat and colorectal cancer could be due in part to mutagens, such as heterocyclic amines (HCA), that are present in cooked meat. HCAs are highly mutagenic and cause intestinal tumors in animals. The hypothesis that HCAs are also carcinogenic to humans remains to be substantiated in epidemiologic studies. We determined the associations of meat preparation and frequency of intake (proxy variables for HCA exposure, since HCA concentration depends on the type of meat and the way it is cooked) with the prevalence of distal colorectal adenomas in a sigmoidoscopy-based case-control study of 488 matched pairs of subjects from two California (United States) Kaiser Permanente Medical Centers. A more than twofold difference in adenoma prevalence between subjects at extreme ends of estimated HCA intake was observed. For subjects who ate red meat more than once per week, fried it more than 10 percent of the time, and ate it with a darkly browned surface, compared with subjects who ate red meat one time or less per week, fried it 10 or less percent of the time, and ate it with a lightly browned surface, the odds ratio was 2.2 (95 percent confidence interval = 1.1-4.3). Adenoma prevalence also increased with frequency of frying red meat (P trend = 0.004). These results are consistent with a carcinogenic effect of HCA.

Adenoma↗

PubMed1997

Recent and past physical activity and prevalence of colorectal adenomas.

Epidemiological evidence has generally supported a protective association of physical activity with large-bowel adenomas, but whether the protective effects are restricted to recent or past activity is uncertain. We determined whether recent and past recreational or total daily activity was associated with prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, aged 50-74 years, completed a 126-item semiquantitative food frequency questionnaire and were also interviewed regarding non-dietary risk factors in 1991-93. In the univariate analysis, all measures of recent recreational physical activity were associated with reduced prevalence of polyps. After adjustment for body mass index, smoking status, daily servings of fruit and vegetables, use of non-steroidal anti-inflammatory agents and intakes of calories, saturated fat and alcohol, the associations were weakened. For subjects engaging in high-intensity activities compared with subjects not engaging in vigorous activities, the multivariate odds ratio (OR) for recent recreational activity was 0.7 [95% confidence interval (CI) 0.4-1.1, trend P = 0.08]. Past recreational activity and past or recent total daily activity were not associated with prevalence of adenomas. These results support a modest association of recent recreational physical activity with prevalence of colorectal adenomas.

Adenoma↗

PubMed1997

Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies.

Phenolphthalein, the active ingredient in many laxatives, was recently found to be a carcinogen in animal models. Human data suggest a laxative-colon cancer association, but few data specifically address the effects of phenolthalein-containing laxatives. We examined use of phenolphtalein-containing laxatives in relation to occurrence of adenomatous colorectal polyps in data from three case-control studies. The study conducted in Los Angeles, California (1991-1993), and the two studies conducted in North Carolina (1988-1990 and 1992-1995) altogether included 866 cases and 1,066 controls. The prevalence of using phenolphthalein-containing laxatives at least once a week in the recent past, however, was less than 5% among these subjects. The multivariate-adjusted odds ratios associated with recent use of phenolphthalein-containing laxatives once a week or more were 1.8 -95% confidence interval (CI), 0.5-6.2] in Los Angeles, 1.0 (CI, 0.4-2.2) in North Carolina (1988-1990), and 1.1 (CI, 0.2-5.7) in North Carolina (1992-1995). For use of other types of laxatives, the corresponding odds ratios were 1.3 (CI, 0.9-1.9) in Los Angeles, 1.0 (CI, 0.5-1.7) in North Carolina (1988-1990), and 0.9 (CI, 0.4-1.8) in North Carolina (1992-1995). Although the low prevalence of frequent use made for relatively wide confidence intervals, overall these data suggest that use of phenolphthalein-containing laxatives does not increase risk of adenomatous colorectal polyps.

Adenomatous Polyps↗

PubMed1997

Strength of linkage disequilibrium between two vitamin D receptor markers in five ethnic groups: implications for association studies.

Markers in the 3' end of the vitamin D receptor gene have recently been associated with prostate cancer risk. To evaluate the adequacy of the commonly used BsmI restriction fragment length polymorphism as a marker of this locus, we genotyped 627 individuals from five ethnic groups for this marker, as well as for a polymorphic site in the 3' untranslated region of this gene. At the latter site, we identified 12 alleles, A13 to A24, of a poly(A) microsatellite. Allele size followed a bimodal distribution with distinct short (A13-A17) and long (A18-A24) allele populations. Poly(A) allele frequency differed by ethnicity, with the frequency of short alleles being highest in non-Hispanic whites (41%), intermediate in Hispanics and African-Americans (31 and 29%, respectively), and lowest in Japanese-Americans and Chinese (8 and 9%, respectively). In each of the ethnic groups, some degree of coupling was observed between BsmI B and short poly(A) alleles and between BsmI b and long poly(A) alleles. However, the strength of the linkage disequilibrium varied by ethnicity, with departures from complete disequilibrium producing disagreement between the BsmI and poly(A) genotypes. Genotypic disagreement was lowest in Japanese-Americans and non-Hispanic whites (6 and 7%, respectively), intermediate in Chinese and Hispanics (11 and 19%, respectively), and highest among African-Americans (37%), indicating that BsmI is not a good marker for the vitamin D receptor 3' untranslated region genotype in all populations. This finding may explain contradictory results from recent association studies using the BsmI marker.

Asian↗

PubMed1997

Hierarchical modeling of gene-environment interactions: estimating NAT2 genotype-specific dietary effects on adenomatous polyps.

Data sparseness currently limits gene-environment interaction estimation. To improve effect estimates of gene-environment interactions, we give an overview of one approach, hierarchical modeling, and propose a two-stage hierarchical model. The first stage is a logistic model for the joint effects of the genetic and environmental factors. The second stage regresses the joint effects on genotype-specific enzymatic activity of the environmentally derived substrate. The model is illustrated using a case-control study of adenomas of the large bowel, for which NAT2 genotype and dietary data were collected. The first-stage interactions of dietary components and genotype were regressed on initial conversion rates of dietary heterocyclic amines to aryl nitrenium ions. We fit the hierarchical model by penalized likelihood. Compared to effect estimates from maximum-likelihood logistic regression, hierarchical results are more reasonable and precise. These results lend further support to previous observations that hierarchical regression is preferable to ordinary logistic regression when multiple factors and their interactions are being studied. We propose that hierarchical modeling can act as a bridge between molecular epidemiology studies and laboratory data, combining both efficiently.

Adenomatous Polyps↗

PubMed1997

Dietary iron and recurrence of colorectal adenomas.

Previous research suggests that iron acts as a prooxidant to increase the risk of colorectal neoplasia. This study examined effects of dietary intake of iron on colorectal adenoma recurrence using data from an antioxidant clinical trial. All subjects were free of polyps at study entry but had at least one adenoma removed within the 3 months before enrollment. Follow-up colonoscopies were conducted after 1 and 4 years. Patients who developed one or more adenomatous polyps between years 1 and 4 were classified as cases; all others were controls. Dietary iron intake at baseline and at the end of the study was estimated from self-administered food frequency questionnaires and averaged together for each subject, energy-adjusted, and categorized into quartiles. Odds ratios were adjusted for age, center, sex, calories, treatment group, and alcohol, fiber, folate, and fat intakes in unconditional logistic regression analysis. Dietary iron was inversely associated with adenoma risk, although risk did not decrease monotonically with increasing intake. Odds ratios comparing second, third, and fourth quartiles to the lowest quartile were 0.61 [95% confidence interval (CI), 0.37-1.02], 0.80 (95% CI, 0.45-1.44), and 0.37 (95% CI, 0.19-0.73), respectively. A limited examination showed no clear evidence that use of iron supplements affected risk of recurrence in this study population. This study provides evidence against the hypothesis that recent dietary intake of iron increases risk for colorectal adenomas. However, these results may reflect the presence of other dietary factors found in combination with iron.

Adenoma↗