Browsing by Author "Sandler, Robert S"

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    Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa.
    (BMC Cancer, 2012-09-05) Vidal, Adriana C; Lund, Pauline Kay; Hoyo, Cathrine; Galanko, Joseph; Burcal, Lauren; Holston, Rachel; Massa, Berri; Omofoye, Oluwaseun; Sandler, Robert S; Keku, Temitope O
    BACKGROUND: Lower concentrations of the insulin-like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC. METHODS: Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models. RESULTS: Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1(st) Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0). CONCLUSIONS: Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender.
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    Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.
    (Clinical epidemiology, 2018-01) Kappelman, Michael D; Lange, Aksel; Randell, Rachel L; Basta, Patricia V; Sandler, Robert S; Laugesen, Kristina; Byrjalsen, Anna; Christensen, Tina; Frøslev, Trine; Erichsen, Rune

    Background

    Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls.

    Subjects and methods

    Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs).

    Results

    A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls.

    Conclusion

    This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.
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    Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites.
    (Cancer Causes Control, 2012-07) Keku, Temitope O; Vidal, Adriana; Oliver, Shannon; Hoyo, Catherine; Hall, Ingrid J; Omofoye, Oluwaseun; McDoom, Maya; Worley, Kendra; Galanko, Joseph; Sandler, Robert S; Millikan, Robert
    PURPOSE: Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)( n ) repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor-binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study. METHODS: Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5'-exonuclease (Taqman) assay. The IGF-I (CA)(n) repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression. RESULTS: The IGF-I (CA)( 19 ) repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)(19) repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15-2.73), but not African Americans (OR = 0.73, 95 % CI 0.50-1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28-0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05). CONCLUSIONS: These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.
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    In Memoriam: Dawn Tranchino Provenzale, MD, MS (August 18, 1955-April 20, 2021).
    (Gastroenterology, 2021-12-22) Dominitz, Jason A; Fisher, Deborah A; Garman, Katherine S; Hunt, Christine M; Lieberman, David; Muir, Andrew J; Onken, Jane E; Robertson, Douglas J; Sandler, Robert S; Sultan, Shahnaz
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    Variation Among Patients With Crohn's Disease in Benefit vs Risk Preferences and Remission Time Equivalents.
    (Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2019-05-14) Bewtra, Meenakshi; Reed, Shelby D; Johnson, F Reed; Scott, Frank I; Gilroy, Erin; Sandler, Robert S; Chen, Wenli; Lewis, James D
    BACKGROUND & AIMS:Patients with Crohn's disease (CD) must make decisions about their treatment. We aimed to quantify patients' preferences for different treatment outcomes and adverse events. We also evaluated the effects of latent class heterogeneity on these preferences. METHODS:An online stated-preference survey was completed by 812 individuals with CD in the Crohn's and Colitis Foundation Partners cohort (IBD Partners). Patients were given information on symptoms and severity of active disease; duration of therapy with corticosteroids; and risks of serious infection, cancer and surgery. Patients were asked to assume that their treatment was not working and to choose an alternative therapy. The primary outcome was remission-time equivalents (RTE) of a given duration of symptom severity or treatment-related risk. Latent class choice models identified groups of patients with dominant treatment-outcome preferences and associated patient characteristics with these groups. RESULTS:Latent class analysis demonstrated 3 distinct groups of survey responders whose choices were strongly influenced by avoidance of active symptoms (61%), avoidance of corticosteroid use (25%), or avoidance of risks of cancer, infection or surgery (14%) when choosing a therapy. Class membership was correlated with age, sex, mean short CD activity index score and corticosteroid avoidance. RTEs in each latent class differed significantly from the mean RTEs for the overall sample, although the symptom-avoidant class most closely approximated the overall sample. CONCLUSIONS:In an online survey of patients with CD, we found substantial heterogeneity in preference for medication efficacy and risk of harm. Physicians and regulators should therefore not assume that all patients have mean-value preferences-this could result in significant differences in health-technology assessment models.
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    Variation in use of surveillance colonoscopy among colorectal cancer survivors in the United States.
    (BMC Health Serv Res, 2010-09-01) Salz, Talya; Weinberger, Morris; Ayanian, John Z; Brewer, Noel T; Earle, Craig C; Elston Lafata, Jennifer; Fisher, Deborah A; Weiner, Bryan J; Sandler, Robert S
    BACKGROUND: Clinical practice guidelines recommend colonoscopies at regular intervals for colorectal cancer (CRC) survivors. Using data from a large, multi-regional, population-based cohort, we describe the rate of surveillance colonoscopy and its association with geographic, sociodemographic, clinical, and health services characteristics. METHODS: We studied CRC survivors enrolled in the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Eligible survivors were diagnosed between 2003 and 2005, had curative surgery for CRC, and were alive without recurrences 14 months after surgery with curative intent. Data came from patient interviews and medical record abstraction. We used a multivariate logit model to identify predictors of colonoscopy use. RESULTS: Despite guidelines recommending surveillance, only 49% of the 1423 eligible survivors received a colonoscopy within 14 months after surgery. We observed large regional differences (38% to 57%) across regions. Survivors who received screening colonoscopy were more likely to: have colon cancer than rectal cancer (OR = 1.41, 95% CI: 1.05-1.90); have visited a primary care physician (OR = 1.44, 95% CI: 1.14-1.82); and received adjuvant chemotherapy (OR = 1.75, 95% CI: 1.27-2.41). Compared to survivors with no comorbidities, survivors with moderate or severe comorbidities were less likely to receive surveillance colonoscopy (OR = 0.69, 95% CI: 0.49-0.98 and OR = 0.44, 95% CI: 0.29-0.66, respectively). CONCLUSIONS: Despite guidelines, more than half of CRC survivors did not receive surveillance colonoscopy within 14 months of surgery, with substantial variation by site of care. The association of primary care visits and adjuvant chemotherapy use suggests that access to care following surgery affects cancer surveillance.