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1.
Endocrinol Metab Clin North Am ; 52(4): 705-717, 2023 12.
Article in English | MEDLINE | ID: mdl-37865483

ABSTRACT

Pituitary adenomas have been increasingly detected in recent years, especially in the older population. Black patients have a higher incidence than other racial groups. In patients with functioning tumors, presentation and comorbidities are influenced by age and sex, whereas the impact of ethnoracial background is unclear. Active surveillance recommendation and surgery refusal disproportionally affect Black and older patients. The likelihood of surgery at high-volume centers is lower for patients of Black or Hispanic background, uninsured or with lower socioeconomic status. Multicentric studies are necessary to delineate the influence of sociodemographic factors according to the adenoma type and to address the causes of health care disparities.


Subject(s)
Adenoma , Pituitary Neoplasms , Humans , Adenoma/diagnosis , Adenoma/epidemiology , Adenoma/ethnology , Adenoma/surgery , Hispanic or Latino/statistics & numerical data , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/ethnology , Pituitary Neoplasms/surgery , Sociodemographic Factors , Black or African American/statistics & numerical data , Medically Uninsured/statistics & numerical data , Low Socioeconomic Status
2.
Int J Cancer ; 153(12): 1978-1987, 2023 12 15.
Article in English | MEDLINE | ID: mdl-37555819

ABSTRACT

Evidence suggests that aspirin use reduces the occurrence of colorectal neoplasia. Few studies have investigated the association among Black Americans, who are disproportionately burdened by the disease. We assessed aspirin use in relation to colorectal adenoma among Black women. The Black Women's Health Study is a prospective cohort of self-identified Black American women established in 1995. Participants reported regular aspirin use on baseline and follow-up questionnaires. Beginning in 1999, participants reported undergoing a colonoscopy or sigmoidoscopy, the only procedures through which colorectal adenomas can be diagnosed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between aspirin use and colorectal adenoma among 34 397 women who reported at least 1 colonoscopy or sigmoidoscopy. From 1997 through 2018, 1913 women were diagnosed with an adenoma. Compared to nonaspirin users, regular users had 14% (OR = 0.86, 95% CI: 0.78-0.95) lower odds of adenoma. The odds of adenoma decreased with increasing duration of aspirin use (≥10 years: OR = 0.80, 95% CI: 0.66-0.96). Initiating aspirin at a younger age was associated with a reduced adenoma occurrence (age < 40 years at initiation: OR = 0.69, 95% CI: 0.55-0.86). Regular aspirin use was associated with a decreased odds of colorectal adenoma in our study of Black women. These findings support evidence demonstrating a chemopreventive impact of aspirin on colorectal neoplasia and suggest that aspirin may be a useful prevention strategy among US Black women.


Subject(s)
Adenoma , Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Black or African American , Colorectal Neoplasms , Adult , Female , Humans , Acetaminophen , Adenoma/epidemiology , Adenoma/ethnology , Adenoma/prevention & control , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/prevention & control , Colorectal Neoplasms/drug therapy , Prospective Studies , United States/epidemiology
3.
Mayo Clin Proc ; 96(5): 1203-1217, 2021 05.
Article in English | MEDLINE | ID: mdl-33840520

ABSTRACT

OBJECTIVE: To estimate the cost-effectiveness of multitarget stool DNA testing (MT-sDNA) compared with colonoscopy and fecal immunochemical testing (FIT) for Alaska Native adults. PATIENTS AND METHODS: A Markov model was used to evaluate the 3 screening test effects over 40 years. Outcomes included colorectal cancer (CRC) incidence and mortality, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The study incorporated updated evidence on screening test performance and adherence and was conducted from December 15, 2016, through November 6, 2019. RESULTS: With perfect adherence, CRC incidence was reduced by 52% (95% CI, 46% to 56%) using colonoscopy, 61% (95% CI, 57% to 64%) using annual FIT, and 66% (95% CI, 63% to 68%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15, 0.17, and 0.19 QALYs per person with colonoscopy, FIT, and MT-sDNA, respectively. Colonoscopy is the most expensive strategy: approximately $110 million more than MT-sDNA and $127 million more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs per person vs 0.05 and 0.06 QALYs per person by FIT and colonoscopy, respectively. Probabilistic sensitivity analyses supported the base-case analysis. Under varied adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs, $1740-$75,868 per QALY saved) compared with FIT and colonoscopy. CONCLUSION: Each strategy reduced costs and increased QALYs compared with no screening. Screening by MT-sDNA results in the largest QALY savings. In Markov model analysis, screening by MT-sDNA in the Alaska Native population was cost-effective compared with screening by colonoscopy and FIT for a wide range of adherence scenarios.


Subject(s)
Adenoma/diagnosis , Colonoscopy/economics , Colorectal Neoplasms/diagnosis , Cost-Benefit Analysis , DNA/analysis , Early Detection of Cancer/methods , Occult Blood , Adenoma/economics , Adenoma/ethnology , Adenoma/metabolism , Adult , Aged , Alaska/epidemiology , Biomarkers/analysis , Biomarkers/metabolism , Colorectal Neoplasms/economics , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/metabolism , Computer Simulation , Early Detection of Cancer/economics , Feces/chemistry , Female , Humans , Incidence , Male , Markov Chains , Middle Aged , Models, Economic , Patient Compliance/statistics & numerical data , Quality-Adjusted Life Years
4.
Fam Cancer ; 20(2): 111-116, 2021 04.
Article in English | MEDLINE | ID: mdl-32743790

ABSTRACT

Germline variants in the APC and MUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence of APC, monoallelic MUTYH and biallelic MUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germline APC and MUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate analysis to compare the frequency of APC and MUTYH variants between AJ and OA, and examined APC p.I1307K and monoallelic MUTYH carrier phenotypes using logistic regression. Pathogenic APC variants occurred in 38/285 AJ (13%) and 1342/6940 OA (19%; P = 0.09); biallelic MUTYH variants in 2/285 (1%) AJ and 399/6940 (6%) OA (P < 0.0001); APC p.I1307K in 35/285 (12%) AJ and 29/6940 (1%) OA (P < 0.0001); and monoallelic MUTYH in 2/285 (1%) AJ and 133/6940 (2%) OA (P = 0.06). Monoallelic MUTYH variants were significantly associated with having a personal history of CRC, regardless of ancestry (OR 1.78; 95% CI 1.21-2.49; P < 0.01), but no significant association was found between APC p.I1307K variants and personal history of CRC (OR 1.38; 95% CI 0.79-2.44; P = 0.26). Ashkenazim with colorectal adenomas rarely have monoallelic or biallelic MUTYH variants, suggesting different genetic etiologies for polyposis in AJ compared to OA individuals. AJ ancestry assessment may be important in clinical evaluation for polyposis.


Subject(s)
Adenoma/genetics , Colorectal Neoplasms/genetics , DNA Glycosylases/genetics , Genes, APC , Germ-Line Mutation/genetics , Jews/genetics , Adenoma/ethnology , Cohort Studies , Colorectal Neoplasms/ethnology , Female , Gene Frequency , Genetic Testing , Humans , Male , Middle Aged , Odds Ratio , Phenotype
5.
Cancer Epidemiol Biomarkers Prev ; 30(1): 3-12, 2021 01.
Article in English | MEDLINE | ID: mdl-33144285

ABSTRACT

Racial disparities in colorectal cancer incidence are widely documented. There are two potential mechanisms for these disparities: differences in access to screening, including screening follow-up, and differences in underlying risk of colorectal cancer. We reviewed the literature for evidence of these two mechanisms. We show that higher colorectal cancer incidence in blacks relative to whites emerged only after the dissemination of screening and describe evidence of racial disparities in screening rates. In contrast to the strong evidence for differences in colorectal cancer screening utilization, there is limited evidence for racial differences in adenoma prevalence. In general, black and white patients who are screened have similar adenoma prevalence, though there is some evidence that advanced adenomas and adenomas in the proximal colon are somewhat more likely in black than white patients. We conclude that higher rates of colorectal cancer incidence among black patients are primarily driven by lower rates of colorectal cancer screening. Our findings highlight the need to increase black patients' access to quality screening to reduce colorectal cancer incidence and mortality.


Subject(s)
Adenoma/ethnology , Colorectal Neoplasms/ethnology , Health Status Disparities , Mass Screening/statistics & numerical data , Adenoma/prevention & control , Black or African American/statistics & numerical data , Colorectal Neoplasms/prevention & control , Humans , Incidence , Outcome Assessment, Health Care/statistics & numerical data , Risk Factors , United States/epidemiology , White People/statistics & numerical data
6.
Signal Transduct Target Ther ; 5(1): 121, 2020 07 08.
Article in English | MEDLINE | ID: mdl-32641705
7.
Cancer Causes Control ; 31(4): 291-302, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32124186

ABSTRACT

PURPOSE: Evidence for the association of anthropometrics with colorectal neoplasms is limited for African Americans. METHODS: We examined anthropometric measures with both colorectal adenoma and colorectal cancer (CRC) risk in the ongoing Black Women's Health Study. In a nested case-control analysis, 954 cases of colorectal adenoma were compared with 3,816 polyp-free controls, matched on age and follow-up time. For the CRC analyses, 413 incident CRC cases were identified over a 16-year follow-up (802,783 person-years). Adenoma cases and CRC were verified by medical record review. We used multivariable conditional logistic regression analyses (for adenoma) and Cox proportional hazards analyses (for CRC) that included anthropometric exposures and selected confounders. RESULTS: Overall body mass index (BMI) and other anthropometric factors were not associated with colorectal adenoma or cancer risk in Black women. However, increased risk of adenoma (but not CRC) was observed among especially related to adenomas in the proximal colon. Among women ≥ 50 years of age, risk of proximal adenoma increased 14% (95% CI 1.00, 1.31), 35% (95% CI 1.12, 1.63), and 25% (0.93, 1.68) with each standard deviation increase in BMI, waist circumference, and waist-to-hip ratio, respectively. None of the anthropometric factors were associated with young onset CRC or adenoma risk. CONCLUSION: Our results suggest that obesity might be an initiator for colon adenomas but not a promoter for colorectal cancer among Black women.


Subject(s)
Adenoma/epidemiology , Black or African American/statistics & numerical data , Colorectal Neoplasms/epidemiology , Obesity/epidemiology , Adenoma/ethnology , Adenoma/etiology , Adult , Anthropometry/methods , Body Mass Index , Case-Control Studies , Cohort Studies , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/etiology , Female , Humans , Incidence , Logistic Models , Male , Obesity/complications , Proportional Hazards Models , Prospective Studies , Risk Factors , Women's Health
8.
Dig Dis Sci ; 65(8): 2412-2418, 2020 08.
Article in English | MEDLINE | ID: mdl-31745688

ABSTRACT

BACKGROUND/AIMS: The black population in the USA is a heterogeneous group composed of smaller subgroups from different origins. The definition of black in many colorectal cancer (CRC) risk studies is vague, and differences in CRC risk comparing black subpopulations have not been evaluated. The aim of the study is to compare advanced colorectal neoplasia (ACN) between two subgroups of black populations: African-American (AA) and Afro-Caribbean (AC). A secondary aim was to determine whether there are differences in prevalence of adenomas. METHODS: This was a retrospective study of 3797 AA and AC patients undergoing first time screening colonoscopy in two different institutions in the USA. RESULTS: Overall adenoma prevalence was 29.3% for the entire population with 29.5% in AAs and 29.0% in AC with no statistically significant difference between the study groups (AOR: 1.02; 95% CI 0.88-1.18, P = 0.751). However, ACN was significantly higher in the AA group (11.8%) compared to AC (9.0%) (AOR: 1.30, 95% CI 1.02-1.66, P = 0.034). It was observed that AAs had ACN at a higher BMI than AC. After adjusting for BMI/ethnicity interactions, the difference in ACN between both groups became more significant (AOR: 1.93, 95% CI 1.16-3.23, P = 0.012). CONCLUSIONS: AAs have a higher risk of ACN than AC. Current recommendations to start screening in average-risk AAs at an earlier age may not apply to other black subgroups.


Subject(s)
Adenoma/ethnology , Black or African American/statistics & numerical data , Colonic Neoplasms/ethnology , Aged , Caribbean Region/ethnology , Female , Florida/epidemiology , Humans , Male , Middle Aged , Ohio/epidemiology , Prevalence , Retrospective Studies
9.
Clin Lab ; 64(9): 1573-1579, 2018 Sep 01.
Article in English | MEDLINE | ID: mdl-30273999

ABSTRACT

BACKGROUND: This study aimed to investigate the detection of methylated Septin 9 (mSEPT9) in Korean patients with colorectal cancer (CRC) and compare the results with those of previous studies. METHODS: A total of 127 plasma samples (111 patients with untreated CRC, 5 patients with adenomas, and 11 CRC patients treated with concurrent chemoradiotherapy before surgery) were collected. mSEPT9 was measured qualitatively with the Abbott RealTime ms9 Colorectal Cancer Assay. RESULTS: mSEPT9 was detected in 44 of 111 (39.6%) cases of untreated CRC but was not detected in the adenoma cases. The difference in the sensitivity of mSEPT9 among patients with adenomas and those with each stage of untreated CRC was statistically significant (Dukes' staging, p = 0.002 and TNM staging, p = 0.008). The sensitivity of mSEPT9 for each of the stages (I - IV) of untreated CRC patients were 20.7%, 54.1%, 36.6%, and 75.0%, respectively. The positive mSEPT9 results in untreated CRC patients reverted to negative in 19 of 21 patients (90.5%) after treatment. CONCLUSIONS: Compared to previous studies, the overall sensitivity of mSEPT9 was lower, but similar patterns were found in the sensitivities for each stage. Additionally, mSEPT9 appeared to have potential as a monitoring tool for CRC.


Subject(s)
Adenoma/genetics , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , DNA Methylation , Septins/genetics , Adenoma/ethnology , Adenoma/pathology , Adenoma/therapy , Adult , Aged , Aged, 80 and over , Asian People/genetics , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/therapy , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Neoplasm Staging , Phenotype , Predictive Value of Tests , Prospective Studies , Real-Time Polymerase Chain Reaction , Republic of Korea/epidemiology
10.
BMC Med Genet ; 19(1): 182, 2018 10 05.
Article in English | MEDLINE | ID: mdl-30290787

ABSTRACT

BACKGROUND: It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the -202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly. METHODS: The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes. RESULTS: The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388-0.909), as well as with the female (OR 0.385, 95% CI 0.206-0.72), macroadenoma (OR 0.557, 95% CI 0.347-0.893) and monotherapy (OR 0.512, 95% CI 0.316-0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331). CONCLUSION: This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.


Subject(s)
Acromegaly/genetics , Adenoma/genetics , Insulin-Like Growth Factor Binding Protein 3/genetics , Pituitary Neoplasms/genetics , Polymorphism, Single Nucleotide , 5' Untranslated Regions , Acromegaly/blood , Acromegaly/complications , Acromegaly/ethnology , Adenoma/blood , Adenoma/complications , Adenoma/ethnology , Adult , Alleles , Asian People , Case-Control Studies , Female , Gene Expression , Gene Frequency , Genotype , Humans , Insulin-Like Growth Factor Binding Protein 3/blood , Male , Middle Aged , Odds Ratio , Pituitary Neoplasms/blood , Pituitary Neoplasms/complications , Pituitary Neoplasms/ethnology , Risk Factors , Sex Factors
11.
Cancer ; 124(19): 3876-3880, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30193399

ABSTRACT

BACKGROUND: Multitarget stool DNA (mt-sDNA) is an approved method for colon cancer screening that is especially relevant for patients who cannot undergo colonoscopy. Although the test performance has been evaluated in a large clinical trial, it was limited to a predominantly white population. Given differences in the epidemiology and biology of colon cancer in African American individuals, the authors sought to compare the performance of mt-sDNA between racial groups. METHODS: The authors prospectively identified patients aged ≥40 years who were referred for colonoscopy at an academic medical center and 2 satellite facilities. Prior to the colonoscopy, the authors collected stool for mt-sDNA and fecal immunochemical testing (FIT). They compared the sensitivity, specificity, and receiver operating characteristic curve between African American and white patients for the detection of advanced lesions or any adenoma. RESULTS: A total of 760 patients were included, 34.9% of whom were African American. The prevalence of any adenoma (38.9% for African American patients and 33.9% for white patients) and that for advanced lesions (6.8% and 6.7%, respectively) were similar between groups. The overall sensitivities of mt-sDNA for the detection of advanced lesions and any adenoma were 43% and 19%, respectively, and the specificities were 91% and 93%, respectively. In general, mt-sDNA was more sensitive and less specific than FIT. When stratified by race, the sensitivity, specificity, and receiver operating characteristic curve area were similar between African American and white patients for both mt-sDNA and FIT. CONCLUSIONS: Test performance characteristics of mt-sDNA were comparable in African American and white patients. Given the lower uptake of colonoscopy in African American individuals, mt-sDNA may offer a promising screening alternative in this patient population.


Subject(s)
Adenoma/diagnosis , Black or African American , Colonic Polyps/diagnosis , Colorectal Neoplasms/diagnosis , DNA, Neoplasm/analysis , Early Detection of Cancer/methods , Occult Blood , Adenoma/ethnology , Adenoma/genetics , Adult , Black or African American/statistics & numerical data , Aged , Aged, 80 and over , Colonic Polyps/ethnology , Colonic Polyps/genetics , Colonoscopy/statistics & numerical data , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/genetics , Early Detection of Cancer/statistics & numerical data , Female , Humans , Male , Mass Screening/methods , Mass Screening/statistics & numerical data , Middle Aged , Sensitivity and Specificity
12.
Clin Lab ; 64(7): 1163-1170, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-30146828

ABSTRACT

BACKGROUND: H. pylori infection has been reported as a risk factor for colorectal adenoma (CRA); however, the clinical results were controversial. Therefore, we performed a meta-analysis to evaluate the association of H. pylori infection and CRA risk. METHODS: A comprehensive literature search for relevant studies published up to November 2017 was performed using Medline and Embase, and the statistical analysis was conducted using Stata software. RESULTS: A total of twenty-five studies including 8,675 cases and 15,275 controls were included in the analysis. The pooled analysis showed that H. pylori infection was associated with an increased risk of CRA (OR = 1.86, 95% CI = 1.55 - 2.23). Subgroup analyses according to the ethnicity, study type, and H. pylori detection method were further conducted. The results showed that H. pylori infection was associated with an increased risk of CRA both in Caucasian (OR = 2.23, 95% CI = 1.36 - 3.66) and Asian population (OR = 1.58, 95% CI = 1.36 - 1.82). Both the case-control studies and cross sectional studies suggested the H. pylori infection could promote the risk of CRA (case control: OR was 2.00, 95% CI = 1.22 - 3.28; cross-sectional: OR was 1.68, 95% CI = 1.43 - 1.99). For H. pylori infection detection methods, there is significant association between H. pylori infection and CRA risk using the serum IgG method and RUT, but not with the UBT and IHC method. CONCLUSIONS: This analysis suggests that H. pylori infection may be a risk factor for CRA.


Subject(s)
Adenoma/diagnosis , Colorectal Neoplasms/diagnosis , Helicobacter Infections/complications , Helicobacter pylori/isolation & purification , Adenoma/chemically induced , Adenoma/ethnology , Asian People/statistics & numerical data , Case-Control Studies , Colorectal Neoplasms/complications , Colorectal Neoplasms/ethnology , Cross-Sectional Studies , Helicobacter Infections/ethnology , Helicobacter Infections/virology , Helicobacter pylori/physiology , Humans , Risk Factors , White People/statistics & numerical data
13.
Dis Colon Rectum ; 61(9): 1073-1079, 2018 09.
Article in English | MEDLINE | ID: mdl-30086056

ABSTRACT

BACKGROUND: Germline mutations in the DNA polymerase genes POLD1 and POLE confer high risk for multiple colorectal adenomas and colorectal cancer. However, prevalence and the clinical phenotype of mutation carriers are still not fully characterized. OBJECTIVE: The purpose of this study was to assess the prevalence of germline mutations and to describe the genotype-phenotype correlation in POLD1 and POLE genes in Jewish subjects with multiple colorectal adenomas and/or early-onset mismatch repair proficient colorectal cancers. DESIGN: This study is a comparison of genetic and clinical data from affected and control groups. SETTINGS: The study was conducted at a high-volume tertiary referral center. PATIENTS: The study cohort included 132 subjects: 68 with multiple colorectal adenomas and 64 with early-onset mismatch repair proficient colorectal cancers. The control group included 5685 individuals having no colorectal cancer or colorectal adenomas. MAIN OUTCOME MEASURES: Study and control subjects were tested for POLD1 and POLE mutations and a clinical correlation was assessed. RESULTS: Eleven of the 132 study subjects (8.3%) carried either a POLD1 or a POLE mutation: 7 of 68 (10.3%) subjects with multiple colorectal adenomas and 4 of 64 (6.2%) subjects with early-onset mismatch repair proficient colorectal cancer. Three mutations were detected, showing statistical significance in frequency between study and control groups (p < 0.001). Eight of the 11 mutation carriers were Ashkenazi Jews carrying the same POLD1 mutation (V759I), implicating it as a possible low-to-moderate risk founder mutation. Phenotype of mutation carriers was notable for age under 50 at diagnosis, a propensity toward left-sided colorectal cancer, and extracolonic tumors (64%, 100%, and 27% of cases). LIMITATIONS: The study cohort was limited by its relatively small size. CONCLUSIONS: Germline mutations in POLD1 and POLE were found to be relatively frequent in our Jewish cohorts. Further studies are needed to clarify the importance of POLD1 and POLE mutations and to define the most suitable surveillance program for Jewish and other POLD1 and POLE mutation carriers. See Video Abstract at http://links.lww.com/DCR/A658.


Subject(s)
Adenoma/genetics , Colorectal Neoplasms/genetics , DNA Polymerase III/genetics , DNA Polymerase II/genetics , Poly-ADP-Ribose Binding Proteins/genetics , Adenoma/ethnology , Adult , Aged , Colorectal Neoplasms/ethnology , DNA Mismatch Repair , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Jews , Male , Middle Aged , Mutation , Prevalence , Registries
14.
Eur J Epidemiol ; 33(1): 15-26, 2018 01.
Article in English | MEDLINE | ID: mdl-29288474

ABSTRACT

The objective of this meta-analysis is to evaluate the odds of colorectal adenoma (CRA) in colorectal cancer screening participants with different body mass index (BMI) levels, and examine if this association was different according to gender and ethnicity. The EMBASE and MEDLINE were searched to enroll high quality observational studies that examined the association between investigator-measured BMI and colonoscopy-diagnosed CRA. Data were independently extracted by two reviewers. A random-effects meta-analysis was conducted to estimate the summary odds ratio (SOR) for the association between BMI and CRA. The Cochran's Q statistic and I2 analyses were used to assess the heterogeneity. A total of 17 studies (168,201 subjects) were included. When compared with subjects having BMI < 25, individuals with BMI 25-30 had significantly higher risk of CRA (SOR 1.44, 95% CI 1.30-1.61; I2 = 43.0%). Subjects with BMI ≥ 30 had similarly higher risk of CRA (SOR 1.42, 95% CI 1.24-1.63; I2 = 18.5%). The heterogeneity was mild to moderate among studies. The associations were significantly higher than estimates by previous meta-analyses. There was no publication bias detected (Egger's regression test, p = 0.584). Subgroup analysis showed that the magnitude of association was significantly higher in female than male subjects (SOR 1.43, 95% CI 1.30-1.58 vs. SOR 1.16, 95% CI 1.07-1.24; different among different ethnic groups (SOR 1.72, 1.44 and 0.88 in White, Asians and Africans, respectively) being insignificant in Africans; and no difference exists among different study designs. In summary, the risk conferred by BMI for CRA was significantly higher than that reported previously. These findings bear implications in CRA risk estimation.


Subject(s)
Adenoma/etiology , Colorectal Neoplasms/etiology , Obesity/complications , Adenoma/ethnology , Adenoma/pathology , Body Mass Index , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/pathology , Colorectal Neoplasms/prevention & control , Female , Humans , Male , Obesity/diagnosis , Obesity/ethnology , Risk Factors
15.
Dig Dis Sci ; 62(6): 1637-1646, 2017 06.
Article in English | MEDLINE | ID: mdl-27913995

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the second leading malignancy diagnosed among US Latinos. Latinos in the USA represent a heterogeneous amalgam of subgroups varying in genetic background, culture, and socioeconomic status. Little is known about the frequency of CRC precursor lesions found at screening colonoscopy among Latino subgroups. AIM: The aim was to determine the prevalence and distribution of histologically confirmed adenomas found at screening colonoscopy among average-risk, asymptomatic US Latinos according to their subgroup and socio-demographic background. METHODS: Cross-sectional analysis of pathological findings resulting from screening colonoscopy among average-risk, asymptomatic US Latinos aged ≥50 in two prospective randomized controlled trials at an academic medical center. RESULTS: Among the 561 Latinos who completed screening colonoscopy, the two largest subgroups were Puerto Ricans and Dominicans. The findings among both subgroups were: adenomas 30.6%, proximal adenomas 23.5%, advanced adenomas 12.0%, and proximal advanced adenomas 8.9%. These rates are at least as high as those found at screening colonoscopy among US whites. While Puerto Ricans were more likely than Dominicans to be born in the USA, speak English, be acculturated, have a smoking history, and be obese, there were no significant differences in adenoma rates between these subgroups. CONCLUSIONS: The prevalence of adenomas, advanced adenomas, and proximal neoplasia was high among both subgroups. These findings have implications for CRC screening and surveillance among the increasingly growing Latino population in the USA.


Subject(s)
Adenoma/ethnology , Adenoma/pathology , Colorectal Neoplasms/ethnology , Colorectal Neoplasms/pathology , Hispanic or Latino/statistics & numerical data , Acculturation , Adenoma/diagnostic imaging , Age Factors , Aged , Colonoscopy , Colorectal Neoplasms/diagnostic imaging , Cross-Sectional Studies , Dominican Republic/ethnology , Early Detection of Cancer , Emigration and Immigration , Female , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Puerto Rico/ethnology , Smoking/ethnology , Socioeconomic Factors , United States/epidemiology
16.
Oncotarget ; 7(47): 77651-77663, 2016 Nov 22.
Article in English | MEDLINE | ID: mdl-27769063

ABSTRACT

BACKGROUND: Recent genome-wide association studies (GWAS) identified eighteen single-nucleotide polymorphisms (SNPs) to be significantly associated with the risk of colorectal cancer (CRC). However, overall results of the following replications are inconsistent and little is known about whether these associations also exit in colorectal adenomas (CRA). METHODS: The SNP genotyping was performed using a Sequenom MassARRAY to investigate the association of these eighteen SNPs with colorectal neoplasm in a case-control study consisted of 1049 colorectal cancers, 283 adenomas, and 1030 controls. RESULTS: Two of these SNPs, rs10505477 and rs719725, showed evidence of an association in both CRC and CRA in our study population. Besides, seven SNPs (rs10808555, rs7014346, rs7837328, rs704017, rs11196172, rs4779584, and rs7229639) were significantly associated with CRC, and another one SNP rs11903757 was over-represented in CRA compared with controls. The strongest association was provided by rs11196172 (OR = 2.02, 95% CI = 1.66 - 2.46, P < 0.0001) and rs11903757 (OR = 1.96, 95% CI = 1.28 - 3.00, P = 0.0026). CONCLUSION: These results suggest that some previously reported SNP associations also have impact on CRC and CRA predispositions in the Han Chinese population. A part of genetic risk to CRC is possibly mediated by susceptibility to adenomas.


Subject(s)
Adenoma/genetics , Asian People/genetics , Colorectal Neoplasms/genetics , Genome-Wide Association Study/methods , Polymorphism, Single Nucleotide , Adenoma/ethnology , Aged , Asian People/ethnology , Case-Control Studies , China/ethnology , Colorectal Neoplasms/ethnology , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged
17.
Endocr J ; 63(11): 953-963, 2016 Nov 30.
Article in English | MEDLINE | ID: mdl-27498687

ABSTRACT

Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported. To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history. Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101) mutations. The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics. The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test. In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed. One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled. The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective. These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained. In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations.


Subject(s)
Adenoma/genetics , Adenoma/pathology , Growth Hormone-Secreting Pituitary Adenoma/genetics , Growth Hormone-Secreting Pituitary Adenoma/pathology , Acromegaly/ethnology , Acromegaly/genetics , Acromegaly/pathology , Adenoma/ethnology , Adolescent , Adult , Case-Control Studies , Child , Chromogranins/genetics , DNA Mutational Analysis , Female , GTP-Binding Protein alpha Subunits, Gs/genetics , Genetic Predisposition to Disease , Growth Hormone-Secreting Pituitary Adenoma/ethnology , Humans , Intracellular Signaling Peptides and Proteins/genetics , Japan/ethnology , Male , Middle Aged , Mutation , Young Adult
18.
Cancer Prev Res (Phila) ; 9(11): 844-854, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27549371

ABSTRACT

Alterations in high order chromatin, with concomitant modulation in gene expression, are one of the earliest events in the development of colorectal cancer. Cohesins are a family of proteins that modulate high-order chromatin, although the role in colorectal cancer remains incompletely understood. We, therefore, assessed the role of cohesin SA1 in colorectal cancer biology and as a biomarker focusing in particular on the increased incidence/mortality of colorectal cancer among African-Americans. Immunohistochemistry on tissue arrays revealed dramatically decreased SA1 expression in both adenomas (62%; P = 0.001) and adenocarcinomas (75%; P = 0.0001). RT-PCR performed in endoscopically normal rectal biopsies (n = 78) revealed a profound decrease in SA1 expression in adenoma-harboring patients (field carcinogenesis) compared with those who were neoplasia-free (47%; P = 0.03). From a racial perspective, colorectal cancer tissues from Caucasians had 56% higher SA1 expression than in African-Americans. This was mirrored in field carcinogenesis where healthy Caucasians expressed more SA1 at baseline compared with matched African-American subjects (73%; P = 0.003). However, as a biomarker for colorectal cancer risk, the diagnostic performance as assessed by area under ROC curve was greater in African-Americans (AUROC = 0.724) than in Caucasians (AUROC = 0.585). From a biologic perspective, SA1 modulation of high-order chromatin was demonstrated with both biophotonic (nanocytology) and chromatin accessibility [micrococcal nuclease (MNase)] assays in SA1-knockdown HT29 colorectal cancer cells. The functional consequences were underscored by increased proliferation (WST-1; P = 0.0002, colony formation; P = 0.001) in the SA1-knockdown HT29 cells. These results provide the first evidence indicating a tumor suppressor role of SA1 in early colon carcinogenesis and as a risk stratification biomarker giving potential insights into biologic basis of racial disparities in colorectal cancer. Cancer Prev Res; 9(11); 844-54. ©2016 AACR.


Subject(s)
Adenocarcinoma/ethnology , Adenoma/ethnology , Biomarkers, Tumor/analysis , Colonic Neoplasms/ethnology , Nuclear Proteins/metabolism , Adenocarcinoma/diagnosis , Adenocarcinoma/metabolism , Adenoma/diagnosis , Adenoma/metabolism , Black or African American , Carcinogenesis , Chromatin , Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , Female , Humans , Incidence , Male , Middle Aged , White People
19.
Ann Surg Oncol ; 23(Suppl 5): 946-953, 2016 12.
Article in English | MEDLINE | ID: mdl-27401449

ABSTRACT

BACKGROUND: Sichuan is a province in the west of China with a population of 81.4 million. This is the first statistical report of central nervous system (CNS) tumors surgically treated and histologically diagnosed in a large Chinese population. METHODS: All the patient data were obtained from 86 medical facilities, which covered the Sichuan province population. Data from patients who underwent surgery between 2008 and 2013 and corresponding histology samples were re-reviewed in the major pathology centers. All the CNS tumors were categorized according to International Classification of Diseases (ICD)-10 and ICD-O-3 classifications and reviewed manually. The tumor distribution was analyzed and stratified by gender, age, race, and tumor sites. Tumors in some ethnic minorities, such as the Tibetan people, also were analyzed. RESULTS: The final analytic dataset included 35,496 records. The top four histologic tumors were meningioma (28.51 %), pituitary adenoma (15.00 %), nerve sheath (13.77 %), and glioblastoma (11.82 %). There was a dramatically high incidence of malignant tumor in males. The median age at diagnosis ranged from 13 years (pineal region tumors) to 56 years (metastatic brain tumors). Most of the tumors in the insular lobe or cerebellum were low grade, whereas those in the thalamus or basal ganglia were likely to be high grade. The incidence of malignant tumors or high-grade gliomas in the Tibetans was significantly lower than in the Chinese Han population. CONCLUSION: This report is a preliminary statistical analysis of brain and spinal tumors in a large Chinese population and may serve as a useful resource for clinicians, researchers, and patients' families.


Subject(s)
Adenoma/epidemiology , Brain Neoplasms/epidemiology , Brain/pathology , Glioblastoma/epidemiology , Meningioma/epidemiology , Nerve Sheath Neoplasms/epidemiology , Spinal Cord Neoplasms/epidemiology , Adenoma/ethnology , Adenoma/pathology , Adolescent , Adult , Age Factors , Brain Neoplasms/ethnology , Brain Neoplasms/pathology , Brain Neoplasms/secondary , Child , Child, Preschool , China/epidemiology , Female , Glioblastoma/ethnology , Glioblastoma/pathology , Humans , Incidence , Infant , Infant, Newborn , Male , Meningioma/ethnology , Meningioma/pathology , Middle Aged , Nerve Sheath Neoplasms/ethnology , Nerve Sheath Neoplasms/pathology , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/pathology , Sex Factors , Spinal Cord Neoplasms/ethnology , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/secondary , Tibet/ethnology , Young Adult
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