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Annals of internal medicine 04/2013; 158(8):639. · 16.73 Impact Factor
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Douglas R Morgan,
Javier Torres,
Rachael Sexton,
Rolando Herrero,
Eduardo Salazar-Martínez,
E Robert Greenberg,
Luis Eduardo Bravo,
Ricardo L Dominguez,
Catterina Ferreccio,
Eduardo C Lazcano-Ponce, [......],
Edgar M Peña,
Rodolfo Peña,
Pelayo Correa, María Elena Martínez,
William D Chey,
Manuel Valdivieso,
Garnet L Anderson,
Gary E Goodman,
John J Crowley,
Laurence H Baker
[show abstract]
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ABSTRACT: The long-term effectiveness of Helicobacter pylori eradication programs for preventing gastric cancer will depend on recurrence risk and individual and community factors.
To estimate risk of H. pylori recurrence and assess factors associated with successful eradication 1 year after treatment.
Cohort analysis of 1463 randomized trial participants aged 21 to 65 years from 7 Latin American communities, who were treated for H. pylori and observed between September 2009 and July 2011.
Randomization to 1 of 3 treatment groups: 14-day lansoprazole, amoxicillin, and clarithromycin (triple therapy); 5-day lansoprazole and amoxicillin followed by 5-day lansoprazole, clarithromycin, and metronidazole (sequential); or 5-day lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant). Participants with a positive (13)C-urea breath test (UBT) 6 to 8 weeks posttreatment were offered voluntary re-treatment with 14-day bismuth-based quadruple therapy.
Recurrent infection after a negative posttreatment UBT and factors associated with successful eradication at 1-year follow-up.
Among participants with UBT-negative results who had a 1-year follow-up UBT (n=1091), 125 tested UBT positive, a recurrence risk of 11.5% (95% CI, 9.6%-13.5%). Recurrence was significantly associated with study site (P = .03), nonadherence to initial therapy (adjusted odds ratio [AOR], 2.94; 95% CI, 1.31-6.13; P = .01), and children in the household (AOR, 1.17; 95% CI, 1.01-1.35 per child; P = .03). Of the 281 with positive posttreatment UBT results, 138 completed re-treatment, of whom 93 tested UBT negative at 1 year. Among the 1340 who had a 1-year UBT, 80.4% (95% CI, 76.4%-83.9%), 79.8% (95% CI, 75.8%-83.5%), and 77.8% (95% CI, 73.6%-81.6%) had UBT-negative results in the triple, sequential, and concomitant groups, respectively (P = .61), with 79.3% overall effectiveness (95% CI, 77.1%-81.5%). In a single-treatment course analysis that ignored the effects of re-treatment, the percentage of UBT-negative results at 1 year was 72.4% (95% CI, 69.9%-74.8%) and was significantly associated with study site (P < .001), adherence to initial therapy (AOR, 0.26; 95% CI, 0.15-0.42; P < .001), male sex (AOR, 1.63; 95% CI, 1.25-2.13; P < .001), and age (AOR, 1.14; 95% CI, 1.02-1.27 per decade; P = .02). One-year effectiveness among all 1463 enrolled participants, considering all missing UBT results as positive, was 72.7% (95% CI, 70.3%-74.9%).
One year after treatment for H. pylori infection, recurrence occurred in 11.5% of participants who had negative posttreatment UBT results. Recurrence determinants (ie, nonadherence and demographics) may be as important as specific antibiotic regimen in determining the long-term success of H. pylori eradication interventions. Study findings are relevant to the feasibility of programs for the primary prevention of gastric cancer in high-incidence regions of Latin America.
clinicaltrials.gov Identifier: NCT01061437.
JAMA The Journal of the American Medical Association 02/2013; 309(6):578-86. · 30.03 Impact Factor
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María Elena Martínez,
Patricia Thompson,
Karen Messer,
Erin L Ashbeck,
David A Lieberman,
John A Baron,
Dennis J Ahnen,
Douglas J Robertson,
Elizabeth T Jacobs,
E Robert Greenberg,
Amanda J Cross,
Wendy Atkin
[show abstract]
[hide abstract]
ABSTRACT: Chinese translation
Guidelines from the United Kingdom and the United States on risk stratification after polypectomy differ, as do recommended surveillance intervals.
To compare risk for advanced colorectal neoplasia at 1-year colonoscopy among patients cross-classified by U.S. and U.K. surveillance guidelines.
Pooled analysis of 4 prospective studies between 1984 and 1998.
Academic and private clinics in the United States.
3226 postpolypectomy patients with 6- to 18-month follow-up colonoscopy.
Rates of advanced neoplasia (an adenoma ≥1 cm, high-grade dysplasia, >25% villous architecture, or invasive cancer) at 1 year, compared across U.S. and U.K. risk categories.
Advanced neoplasia was detected 1 year after polypectomy in 3.8% (95% CI, 2.7% to 4.9%) of lower-risk patients and 11.2% (CI, 9.8% to 12.6%) of higher-risk patients by U.S. criteria. According to U.K. criteria, 4.4% (CI, 3.3% to 5.4%) of low-risk patients, 9.9% (CI, 8.3% to 11.5%) of intermediate-risk patients, and 18.7% (CI, 14.8% to 22.5%) of high-risk patients presented with advanced neoplasia; U.K. high-risk patients comprised 12.1% of all patients. All U.S. lower-risk patients were low-risk by U.K. criteria; however, more patients were classified as low-risk, because the U.K. guidelines do not consider histologic features. Higher-risk U.S. patients were distributed across the 3 U.K. categories. Among all patients with advanced neoplasia, 26.3% were reclassified by the U.K. criteria to a higher-risk category and 7.0% to a lower-risk category, with a net 19.0% benefiting from detection 2 years earlier. Overall, substitution of U.K. for U.S. guidelines resulted in an estimated 0.03 additional colonoscopy every 5 years per patient.
Patients were enrolled 15 to 20 years ago, and quality measures for colonoscopy were unavailable. Patients lacking follow-up colonoscopy or with surveillance colonoscopy after 6 to 18 months and those with cancer or insufficient baseline adenoma characteristics were excluded (2076 of 5302).
Application of the U.K. guidelines in the United States could identify a subset of high-risk patients who may warrant a 1-year clearing colonoscopy without substantially increasing rates of colonoscopy.
European Union Public Health Programme.
Annals of internal medicine 12/2012; 157(12):856-64. · 16.73 Impact Factor
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Giovanna I Cruz, María Elena Martínez,
Loki Natarajan,
Betsy C Wertheim,
Manuela Gago-Dominguez,
Melissa Bondy,
Adrian Daneri-Navarro,
María Mercedes Meza-Montenegro,
Luis Enrique Gutierrez-Millan,
Abenaa Brewster,
Pepper Schedin,
Ian K Komenaka,
J Esteban Castelao,
Angel Carracedo,
Carmen M Redondo,
Patricia A Thompson
[show abstract]
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ABSTRACT: Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (≤10 or >10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies ≥1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of ≤10 years (OR = 1.68; 95 % CI, 1.12-2.52). The effect was present across all source populations and independent of the HR status of the HER2+ tumor. Adjusting for age at diagnosis (≤45 or >45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors.
Breast Cancer Research and Treatment 11/2012; · 4.43 Impact Factor
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María Elena Martínez,
Erika Pond,
Betsy C Wertheim,
Jesse N Nodora,
Elizabeth T Jacobs,
Melissa Bondy,
Adrian Daneri-Navarro,
Maria Mercedes Meza-Montenegro,
Luis Enrique Gutierrez-Millan,
Abenaa Brewster,
Ian K Komenaka,
Patricia Thompson
[show abstract]
[hide abstract]
ABSTRACT: Obesity at diagnosis of breast cancer is associated with higher all-cause mortality and treatment-associated toxicities. We evaluated the association between parity and obesity in the Ella study, a population of Mexican and Mexican-American breast cancer patients with high parity. Obesity outcomes included body mass index (BMI) ≥30 kg/m(2), waist circumference (WC) ≥35 in (88 cm), and waist-to-hip-ratio (WHR) ≥0.85. Prevalence of obesity ([BMI] ≥ 30 kg/m(2)) was 38.9 %. For WC, the multivariate odds ratio (OR) (95 % confidence interval [CI]) for having WC ≥ 35 inches in women with ≥4 pregnancies relative to those with 1-2 pregnancies was 1.59 (1.01-2.47). Higher parity (≥4 pregnancies) was non-significantly associated with high BMI (OR = 1.10; 95 % CI 0.73-1.67). No positive association was observed for WHR. Our results suggest WC is independently associated with high parity in Hispanic women and may be an optimal target for post-partum weight loss interventions.
Journal of Immigrant and Minority Health 05/2012; · 1.16 Impact Factor
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[show abstract]
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ABSTRACT: Nutritional supplementation is now a multibillion-dollar industry, and about half of all US adults take supplements. Supplement use is fueled in part by the belief that nutritional supplements can ward off chronic disease, including cancer, although several expert committees and organizations have concluded that there is little to no scientific evidence that supplements reduce cancer risk. To the contrary, there is now evidence that high doses of some supplements increase cancer risk. Despite this evidence, marketing claims by the supplement industry continue to imply anticancer benefits. Insufficient government regulation of the marketing of dietary supplement products may continue to result in unsound advice to consumers. Both the scientific community and government regulators need to provide clear guidance to the public about the use of dietary supplements to lower cancer risk.
CancerSpectrum Knowledge Environment 04/2012; 104(10):732-9. · 14.07 Impact Factor
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Carmen M Redondo,
Manuela Gago-Domínguez,
Sara Miranda Ponte,
Manuel Enguix Castelo,
Xuejuan Jiang,
Ana Alonso García,
Maite Peña Fernández,
María Ausencia Tomé,
Máximo Fraga,
Francisco Gude, María Elena Martínez,
Víctor Muñoz Garzón,
Ángel Carracedo,
J Esteban Castelao
[show abstract]
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ABSTRACT: BACKGROUND: Differences in the incidence and outcome of breast cancer among Hispanic women compared with white women are well documented and are likely explained by ethnic differences in genetic composition, lifestyle, or environmental exposures. METHODOLGY/PRINCIPAL FINDINGS: A population-based study was conducted in Galicia, Spain. A total of 510 women diagnosed with operable invasive breast cancer between 1997 and 2010 participated in the study. Data on demographics, breast cancer risk factors, and clinico-pathological characteristics were collected. The different breast cancer tumor subtypes were compared on their clinico-pathological characteristics and risk factor profiles, particularly reproductive variables and breastfeeding. Among the 501 breast cancer patients (with known ER and PR receptors), 85% were ER+/PR+ and 15% were ER-&PR-. Among the 405 breast cancer with known ER, PR and HER2 status, 71% were ER+/PR+/HER2- (luminal A), 14% were ER+/PR+/HER2+ (luminal B), 10% were ER-/PR-/HER2- (triple negative breast cancer, TNBC), and 5% were ER-/PR-/HER2+ (non-luminal). A lifetime breastfeeding period equal to or longer than 7 months was less frequent in case patients with TNBC (OR = 0.25, 95% CI = 0.08-0.68) compared to luminal A breast cancers. Both a low (2 or fewer pregnancies) and a high (3-4 pregnancies) number of pregnancies combined with a long breastfeeding period were associated with reduced odds of TNBC compared with luminal A breast cancer, although the association seemed to be slightly more pronounced among women with a low number of pregnancies (OR = 0.09, 95% CI = 0.005-0.54). CONCLUSIONS/SIGNIFICANCE: In case-case analyses with the luminal A cases as the reference group, we observed a lower proportion of TNBC among women who breastfed 7 or more months. The combination of longer breastfeeding duration and lower parity seemed to further reduce the odds of having a TNBC compared to a luminal A breast cancer.
PLoS ONE 01/2012; 7(7):e40543. · 4.09 Impact Factor
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Rachel Zenuk Garcia,
Scott C Carvajal,
Anna V Wilkinson,
Patricia A Thompson,
Jesse N Nodora,
Ian K Komenaka,
Abenaa Brewster,
Giovanna I Cruz,
Betsy C Wertheim,
Melissa L Bondy, María Elena Martínez
[show abstract]
[hide abstract]
ABSTRACT: This study examined factors that influence mammography use and breast cancer detection, including education, health insurance, and acculturation, among Mexican-American (MA) and African-American (AA) women.
The study included 670 breast cancer cases (388 MAs and 282 AAs), aged 40-86 years at diagnosis. Data on mammography use, detection, and delay in seeking care were collected via questionnaires and medical records. Using a language-based bidimensional acculturation measure, MAs were classified as English-dominant (n = 67), bilingual (n = 173), and Spanish-dominant (n = 148). Mammography prior to diagnosis was assessed by racial/ethnic acculturation subgroup using logistic regression.
In age-adjusted models, mammography use was non-significantly lower among English-dominant (OR = 0.84; 95% CI: 0.45-1.59) and bilingual (OR = 0.86; 95% CI: 0.55-1.35) MAs and significantly lower among Spanish-dominant MAs (OR = 0.53; 95% CI: 0.34-0.83) than among AA women. After adjustment for education or insurance, there was no difference in mammography use by race/ethnicity and acculturation subgroup. Despite high self-reported mammography use (75%), a large proportion of cases reported self-detection (59%) and delay in seeking care >90 days (17%).
These findings favor promoting culturally appropriate messaging about the benefits and limitations of mammography, education about breast awareness, and prompt reporting of findings to a health professional.
Cancer Causes and Control 11/2011; 23(1):165-73. · 2.88 Impact Factor
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E Robert Greenberg,
Garnet L Anderson,
Douglas R Morgan,
Javier Torres,
William D Chey,
Luis Eduardo Bravo,
Ricardo L Dominguez,
Catterina Ferreccio,
Rolando Herrero,
Eduardo C Lazcano-Ponce,
María Mercedes Meza-Montenegro,
Rodolfo Peña,
Edgar M Peña,
Eduardo Salazar-Martínez,
Pelayo Correa, María Elena Martínez,
Manuel Valdivieso,
Gary E Goodman,
John J Crowley,
Laurence H Baker
[show abstract]
[hide abstract]
ABSTRACT: Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.
Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437.
1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites.
Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations.
Bill & Melinda Gates Foundation, US National Institutes of Health.
The Lancet 08/2011; 378(9790):507-14. · 38.28 Impact Factor
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ABSTRACT: To assess self-reported compliance to colorectal cancer (CRC) screening guidelines among primary care physicians (PCPs) and to assess physician and practice characteristics associated with reported compliance.
Survey data from 984 PCPs in Arizona were used. Self-reported CRC screening practices, recommendations, and compliance with guidelines were assessed. Physician and practice characteristics associated with guideline compliance were also evaluated.
While 77.5% of physicians reported using national screening guidelines, only 51.7% reported recommendations consistent with the guidelines. Younger physicians were significantly more likely to report compliance with screening guidelines (OR = 1.50, 95% CI = 1.07-2.10) as were female clinicians (OR = 1.46, 95% CI = 1.11-1.92). Physicians practicing in solo (OR = 0.33, 95% CI = 0.19-0.58), group (OR = 0.36, 95% CI = 0.21-0.62), or community health centers (OR = 0.37, 95% CI = 0.17-0.81) were significantly less likely to report following guidelines as compared to those in academic practice. Guideline compliance was higher for fecal occult blood test (FOBT) (65.0%) than colonoscopy (56.7%); overuse of screening for these modalities was reported among 34.4% of physicians.
PCPs are not adequately following CRC screening guidelines. Further studies are needed to clarify the reasons for this lack of compliance, especially as guidelines become more complex.
Cancer Causes and Control 06/2011; 22(9):1277-87. · 2.88 Impact Factor
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[show abstract]
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ABSTRACT: The field of vitamin D and cancer research has been moving forward quickly. However, some challenges remain regarding the interpretation and integration of data collected from epidemiological investigations and laboratory experiments. These include consideration of vitamin D biology, a better understanding of characteristics that affect concentrations of the biomarker of vitamin D status, 25(OH)D, and elucidation of variation in response to vitamin D supplementation. To further the field of vitamin D and cancer prevention, future studies will need to bridge the gap between the epidemiology and molecular biology of vitamin D activity in carcinogenesis.
Cancer Epidemiology Biomarkers & Prevention 04/2011; 20(4):585-90. · 4.12 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Insulin and insulin-like growth factor (IGF) genes are implicated in colorectal carcinogenesis. Gene-by-gene interactions that influence the insulin/IGF pathways were hypothesized as modifiers of colorectal neoplasia risk. We built a classification tree to detect interactions in 18 IGF and insulin pathway-related genes and metachronous colorectal neoplasia among 1,439 subjects pooled from two chemoprevention trials. The probability of colorectal neoplasia was greatest (71.8%) among carriers of any A allele for rs7166348 (IGF1R) and AA genotype for rs1823023 (PIK3R1). In contrast, carriers of any A at rs7166348 (IGF1R), any G for the PIK3R1 variant, and AA for rs10426094 (INSR) had the lowest probability (14.3%). Logistic regression modeling showed that any A at rs7166348 (IGF1R) with the AA genotype at rs1823023 (PIK3R1) conferred the highest odds of colorectal neoplasia (OR 3.7; 95% CI 2.2-6.5), compared with carriage of GG at rs7166348 (IGF1R). Conversely, any A at rs7166348 (IGFR1), any G allele at rs1823023 (PIK3R1), and the AA genotype at rs10426094 (INSR) conferred the lowest odds (OR 0.22; 95% CI 0.07-0.66). Stratifying the analysis by parent study and intervention arm showed highly consistent trends in direction and magnitude of associations, with preliminary evidence of genotype effects on measured IGF-1 levels in a subgroup of subjects. These results were compared to those from multifactor dimensionality reduction, which identified different single nucleotide polymorphisms in the same genes (INSR and IGF1R) as effect modifiers for colorectal neoplasia. These results support a role for genetic interactions in the insulin/IGF pathway genes in colorectal neoplasia risk.
Human Genetics 01/2011; 129(5):503-12. · 5.07 Impact Factor
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Cancer Epidemiology Biomarkers & Prevention 11/2010; 19(11):2710-4. · 4.12 Impact Factor
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CancerSpectrum Knowledge Environment 06/2010; 102(11):749-51. · 14.07 Impact Factor
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Peter T Campbell,
Elizabeth T Jacobs,
Cornelia M Ulrich,
Jane C Figueiredo,
Jenny N Poynter,
John R McLaughlin,
Robert W Haile,
Eric J Jacobs,
Polly A Newcomb,
John D Potter, [......],
H Banfield Younghusband,
Michelle Cotterchio,
Steven Gallinger,
Mark A Jenkins,
John L Hopper,
John A Baron,
Stephen N Thibodeau,
Noralane M Lindor,
Paul J Limburg, María Elena Martínez
[show abstract]
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ABSTRACT: Being overweight or obese is an established risk factor for colorectal cancer, more so for men than for women. Approximately 10%-20% of colorectal tumors display microsatellite instability (MSI), defined as the expansion or contraction of small repeated sequences in the DNA of tumor tissue relative to nearby normal tissue. We evaluated associations between overweight or obesity and colorectal cancer risk, overall and by tumor MSI status.
The study included 1794 case subjects with incident colorectal cancer who were identified through population-based cancer registries and 2684 of their unaffected sex-matched siblings as control subjects. Recent body mass index (BMI), BMI at age 20 years, and adult weight change were derived from self-reports of height and weight. Tumor MSI status, assessed at as many as 10 markers, was obtained for 69.7% of the case subjects and classified as microsatellite (MS)-stable (0% of markers unstable; n = 913), MSI-low (>0% but <30% of markers unstable; n = 149), or MSI-high (> or =30% of markers unstable; n = 188). Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided.
Recent BMI, modeled in 5 kg/m(2) increments, was positively associated with risk of colorectal cancer for men and women combined (OR = 1.24; 95% CI = 1.15 to 1.34), for women only (OR = 1.20; 95% CI = 1.10 to 1.32), and for men only (OR = 1.30; 95% CI = 1.15 to 1.47). There was no interaction with sex (P = .22). Recent BMI, per 5 kg/m(2), was positively associated with the risk of MS-stable (OR = 1.38; 95% CI = 1.24 to 1.54) and MSI-low (OR = 1.33; 95% CI = 1.04 to 1.72) colorectal tumors, but not with the risk of MSI-high tumors (OR = 1.05; 95% CI = 0.84 to 1.31).
The increased risk of colorectal cancer associated with a high BMI might be largely restricted to tumors that display the more common MS-stable phenotype, suggesting further that colorectal cancer etiology differs by tumor MSI status.
CancerSpectrum Knowledge Environment 03/2010; 102(6):391-400. · 14.07 Impact Factor
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Jan B Egan,
Patricia A Thompson,
Erin L Ashbeck,
David V Conti,
David Duggan,
Elizabeth Hibler,
Peter W Jurutka,
Elizabeth C Leroy, María Elena Martínez,
David Mount,
Elizabeth T Jacobs
[show abstract]
[hide abstract]
ABSTRACT: Low circulating levels of vitamin D affect colorectal cancer risk. The biological actions of the hormonal form of vitamin D, 1,25(OH)(2)D(3), are mediated by the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptors (RXR). Using a single nucleotide polymorphism (SNP) tagging approach, we assessed the association between genetic variations in RXRA and VDR and odds of recurrent (metachronous) colorectal neoplasia in a pooled population of two studies. A total of 32 tag SNPs in RXRA and 42 in VDR were analyzed in 1,439 participants. A gene-level association was observed for RXRA and any (P = 0.04) or proximal (P = 0.03) metachronous neoplasia. No gene-level associations were observed for VDR, nor was any single SNP in VDR related to any metachronous adenoma after correction for multiple comparisons. In contrast, the association between RXRA SNP rs7861779 and proximal metachronous neoplasia was of borderline statistical significance [odds ratio (OR), 0.68; 95% confidence interval (95% CI), 0.53-0.86; unadjusted P = 0.001; adjusted P = 0.06], including when observed independently in each individual study. Haplotypes within linkage blocks of RXRA support an approximately 30% reduction in odds of metachronous neoplasia arising in the proximal colon among carriers of specific haplotypes, which was strongest (OR(proximal), 0.67; 95% CI, 0.52-0.86) for carriers of a CGGGCA haplotype (rs1805352, rs3132297, rs3132296, rs3118529, rs3118536, and rs7861779). Our results indicate that allelic variation in RXRA affects metachronous colorectal neoplasia, perhaps of particular importance in the development of proximal lesions.
Cancer Research 02/2010; 70(4):1496-504. · 7.86 Impact Factor
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ABSTRACT: Ursodeoxycholic acid (UDCA) was one of the earliest agents investigated as a drug for colorectal cancer prevention. However, UDCA failed to show efficacy to prevent the development of colorectal adenomas in a large, phase III, randomized, placebo-controlled trial. We re-evaluated the effect of UDCA in men and women separately, based on sex-specific differences in bile acid metabolism and suspected variation in etiologic factors contributing to colorectal cancer risk.
We conducted a secondary analysis of the efficacy of UDCA to prevent colorectal adenoma in men (n = 804) and women (n = 388).
We found no reduction in risk of any metachronous adenoma with UDCA treatment in men or women. However, UDCA treatment significantly lowered the odds of advanced lesions [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.43-0.89] in men, but not women. We also observed significantly higher odds of advanced lesions with UDCA treatment in women who were younger (age, <65 years; OR, 3.24; 95% CI, 1.10-9.56), obese (body mass index, > or = 30 kg/m(2); OR, 5.45; 95% CI, 1.42-20.9), or in the highest tertile of total dietary fat (> or = 56.2 g/day; OR, 3.48; 95% CI, 1.35-8.95). In a multivariate model, the interactive effect of fat intake accounted for the modulating effects of age and body mass index in women.
Our findings support the use of UDCA for preventing advanced colorectal adenomas in men. The increased odds of adenoma among women with high fat intake suggest a previously unrecognized harm that warrants further study, especially given the chronic exposure to UDCA in patients with primary biliary cirrhosis and the increasing investigational use of UDCA for several other conditions.
Cancer Prevention Research 12/2009; 2(12):1023-30. · 4.91 Impact Factor
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[show abstract]
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ABSTRACT: Physical activity is protective against colon cancer, whereas colonic bile acid exposure is a suspected risk factor. Although likely related, the association between physical activity and bile acid levels has not been well-studied. Furthermore, the effect of triglycerides, which are known to modify bile acid levels, on this relationship has not been investigated. We conducted a cross-sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma formers obtained from participants in a phase III ursodeoxycholic acid chemoprevention trial. Compared with the lowest quartile of recreational physical activity duration, the highest quartile was associated with a 17% lower fecal bile acid concentration, adjusted for age, sex, dietary fiber intake, and body mass index (P = 0.042). Furthermore, consistent with a previously established relationship between serum triglyceride levels and bile acid metabolism, we stratified by triglyceride level and observed a 34% lower fecal bile acid concentration (highest versus lowest quartiles of physical activity) in individuals with low triglycerides (<136 mg/dL; P = 0.002). In contrast, no association between physical activity and fecal bile acid concentration was observed for subjects with high triglycerides (> or =136 mg/dL). Our results suggest that the biological mechanism responsible for the protective effect of physical activity on the incidence of colon cancer may be partially mediated by decreasing colonic bile acid exposure. However, this effect may be limited to individuals with lower triglyceride levels.
Cancer Epidemiology Biomarkers & Prevention 05/2009; 18(5):1591-8. · 4.12 Impact Factor
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[show abstract]
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ABSTRACT: The consistent association between obesity and colorectal cancer is thought to be explained by metabolic disturbances common, but not exclusive, to the obese.
We assessed the relation between metachronous neoplasia and the components of metabolic syndrome (MetS) as defined by the National Cholesterol Education Program's Adult Treatment Panel III in 2,392 participants of two previously conducted chemoprevention trials. Waist circumference, fasting plasma glucose, trigylcerides, high-density lipoprotein, and systolic and diastolic blood pressure were measured at baseline.
MetS classification was associated with increased odds of metachronous neoplasia among women [odds ratio (OR), 1.37; 95% confidence interval (95% CI), 1.01-1.85] but not among men (OR, 0.99; 95% CI, 0.81-1.21). High waist circumference in men (OR, 1.41; 95% CI, 1.15-1.72) and women (OR, 1.41; 95% CI, 1.05-1.90) and elevated fasting glucose in women (OR, 1.46; 95% CI, 1.09-1.96), as defined by Adult Treatment Panel III cutpoints, were associated with increased odds, whereas none of the other criteria were independently associated with metachronous neoplasia. When each trait was evaluated using quartiles, elevated glucose among women and large waist circumference among men were significantly associated with metachronous lesions. Exploratory analysis of waist circumference and fasting glucose suggested an interaction, where only the combination of large waist circumference and elevated glucose conferred significant increased odds of metachronous neoplasia among both men (OR, 1.36; 95% CI, 1.04-1.78; P(interaction) = 0.08) and women (OR, 1.83; 95% CI, 1.26-2.67; P(interaction) = 0.12).
These results suggest that, of the specific components of MetS, those that capture impaired glucose uptake increased the odds of metachronous neoplasia.
Cancer Epidemiology Biomarkers & Prevention 05/2009; 18(4):1134-43. · 4.12 Impact Factor
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Cancer Prevention Research 04/2009; 2(3):197-9. · 4.91 Impact Factor
