The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 ± 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 ± 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted.
Lynch syndrome (LS) is an autosomal dominant disorder caused by DNA mismatch repair (MMR) system deficiencies. Women affected by LS present a 40 to 60% lifetime risk of endometrial cancer (EC). Objective This case-case study aims to determine the frequency of the hMLH1, hMSH2, and hMSH6 MMR proteins and the factors (age, family history of cancer [FHC] related to LS, and body mass index [BMI]) associated to their absence in EC patients attending the University District Hospital of San Juan, Puerto Rico. Method/Materials Twenty cases were preliminary evaluated for the MMR protein expression by immunohistochemistry testing and classified as positive-cases (presence of protein) or negative-cases (absence of protein). The statistical analysis was based on the logistic regression model using the Maximum Likelihood estimation (MLE). The Bayesian approach was used to determine the posterior probability {posterior Pr[OR>1]}. Results Results showed absence for at least one MMR protein in 25% of the cases; 15% for hMLH1 and 10% for hMSH2. None of the cases showed an absence for hMSH6. The MLE demonstrated that women diagnosed with EC before the age of 50 (OR: 12.4; 95%CI = 0.5–322.7), having FHC related to LS (OR: 17.7; 95%CI = 0.6–534.6), and having lower BMI (OR: 2.38; 95%CI = 0.39–14.28) present higher odds than their counterparts of lacking an MMR protein, once adjusting for potential predictors (p > .05). The posterior probability that an excess risk of lacking an MMR protein occurs was ≥ 95% for each predictor. Conclusion Our study in this Hispanic population supports previous studies in that younger age, FHC, and lower BMI are associated with increased odds of having an absence of MMR protein expression. Further studies with larger sample sizes should be performed.
Background: In Puerto Rico (PR), colorectal cancer (CRC) represents the second most common cause of cancer in men and women. Incidence and mortality of CRC are increasing in Puerto Rican Hispanics, especially among young individuals. Screening rates for CRC are lower in Hispanic-American individuals compared to non-Hispanic patients. However, there is limited data on genetic epidemiological CRC disparities in Hispanic patients. Objectives: (1) To prospectively identify and recruit 30 probands with a family history of CRC and 15 family-history negative. (2) To prospectively identify and recruit selected relatives from the 45 probands. Methods: Eligible cases are Hispanic patients with incident diagnosis of CRC, ≥ 21 years old. We identified the probands and their selected family members using the Puerto Rico Central Cancer Registry from July 1, 2007 to the present. Preliminary data and recruitment: Seven hundred and fifty-one communications were sent to the physicians, three hundred and seventy-four communications were responded (374/751=49.8%). Three hundred and forty-one communications were sent to the patients, one hundred and forty-seven letters were responded (147/341=43.1%) and 16 refused. One hundred and fifty-nine participants (probands and relatives) were enrolled. One-hundred and two probands (mean age 56.9 ± 13.3 yrs., 54.9% male); 30 with and 72 without family history of CRC. At present, we collected 153 (96.2%) risk factors questionnaires, 135 (84.9%) blood samples and 60 (52.6%) blocks of tissue. Successful implementation of logistics for identification of incident CRC through the PR Central Cancer Registry during a three-year period. We established the first Familial CRC island-wide registry in Puerto Rico through the implementation of a network of community physicians, laboratories and professional societies. We are developing a tissue and blood bank with epidemiological, nutritional, and demographic data that will assist us to understand the genetic epidemiology of CRC in Puerto Ricans. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A68.
Introduction: Approximately 10% to 15% of all sporadic colorectal cancers have microsatellite instability (MSI). MSI has not been well studied in Hispanics, an ethnic minority at high risk for colorectal cancer (CRC). Patients with MSI tumors present with better prognosis, higher 5-year survival and limited response to 5-FU based chemotherapy, compared to microsatellite stable (MSS) tumors. The aim of this study was to define the clinic-pathologic phenotype of Hispanics with sporadic MSI CRC and to evaluate the association of dietary factors and tumor MSI-status. Methods: The case-case study evaluated the MSI status of sporadic CRC diagnosed during the period January 1, 2002 to October 31, 2012. MSI analysis was performed using six markers (BAT26, BAT25, NR21, NR22, NR24 and NR27). Tumors were classified as MSI-high if two or more of the six microsatellite repeats were mutated and MSS if none of the replicates was mutated. Frequency analysis, chi-square, Fisher's exact test and Wilcoxon rank-sum test were used for statistical analysis methods. Unconditional logistic regression was employed to estimate the odds ratio (OR) between exposures and MSI using STATA 10.0. Results: A total of 85 participants (mean age 57.5 ± 12.5 yrs, 51.8% males) were examined. 80 patients had MSS tumors, while 5 (6%) tumors had MSI. The colorectal neoplasia specimens analyzed were mostly adenocarcinomas (96.5%) located in the distal colon (72.0%) with TNM stage III (34.4%). Tumors with MSI did not significantly differ from MSS tumors with regards to gender (p=0.36), age (p=0.66), education (p>0.99), family history of CRC (p=0.58) or obesity (p>0.99). MSI tumors were more likely located in the proximal colon compared to MSS tumors (OR=12.21; 95% CI 1.4-306.6). There were no statistical significant associations between MSI and reported consumption of dark green leaf vegetables (2-4 times/week) (OR=0.77; 95% CI 0.11-6.88), fruits (≥ 7 times/week) (OR=3.54; 95% CI 0.24-108.52) and red meats (once per day) (OR=1.08; 95% CI: 0.04-9.55). Conclusions: We report a lower prevalence of MSI in Hispanics with sporadic CRC than other Western populations. As previously reported in other non-Hispanic populations, MSI tumors were mostly located in the proximal colon. There were no statistical significant associations between sociodemographic, clinical and nutritional characteristics and MSI. Ongoing efforts to continue to examine additional Hispanic patients are underway to determine if dietary patterns in Hispanics are associated with CRC MSI status. Citation Format: Yaritza Diaz-Algorri, Sofia Margarita Lopez-Diaz, Maria del Mar Gonzalez-Pons, Katerina Freyre, Maritere Olascoaga, Sylvia B. Saldaña-Villafañe, Mercedes Y. Lacourt-Ventura, Sharon C. Fonseca-Williams, Raul D. Bernabe-Dones, Xavier LLord, Rosa Xicola, Katherine Tucker, Marcia R. Cruz-Correa. Clinicopathological characterization and nutritional assessment of Hispanics with sporadic microsatellite unstable colorectal cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 109. doi:10.1158/1538-7445.AM2013-109
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