High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study.

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.

Detection of DNA damage in peripheral blood mononuclear cells from pancreatic cancer patients.

DNA repair is a key mechanism in maintaining genomic stability: repair deficiencies increase DNA damage and mutations that lead to several diseases, including cancer. We extracted DNA from peripheral blood mononuclear cells (PBMCs) of 48 pancreatic adenocarcinoma cases and 48 healthy controls to determine relative levels of nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage by QPCR. All participants were never smokers and between the ages of 60 and 69. Average levels among cases were compared to controls using a rank sum test, and logistic regression adjusted for potential confounding factors (age, sex, and diabetes mellitus). Cases had less DNA damage, with a significant decrease in mtDNA damage (P-value = 0.03) and a borderline significant decrease in nDNA damage (P = 0.08). Across samples, we found mtDNA abundance was higher among non-diabetics compared to diabetics (P = 0.04). Our results suggest that patients with pancreatic adenocarcinoma have less DNA damage in their PBMCs, and that having diabetes, a known pancreatic cancer risk factor, is associated with lower levels of mtDNA abundance.

Requirement of the Saccharomyces cerevisiae APN1 gene for the repair of mitochondrial DNA alkylation damage.

The Saccharomyces cerevisiae APN1 gene that participates in base excision repair has been localized both in the nucleus and the mitochondria. APN1 deficient cells (apn1 Delta) show increased mutation frequencies in mitochondrial DNA (mtDNA) suggesting that APN1 is also important for mtDNA stability. To understand APN1-dependent mtDNA repair processes we studied the formation and repair of mtDNA lesions in cells exposed to methyl methanesulfonate (MMS). We show that MMS induces mtDNA damage in a dose-dependent fashion and that deletion of the APN1 gene enhances the susceptibility of mtDNA to MMS. Repair kinetic experiments demonstrate that in wild-type cells (WT) it takes 4 hr to repair the damage induced by 0.1% MMS, whereas in the apn1 Delta strain there is a lag in mtDNA repair that results in significant differences in the repair capacity between the two yeast strains. Analysis of lesions in nuclear DNA (nDNA) after treatment with 0.1% MMS shows a significant difference in the amount of nDNA lesions between WT and apn1 Delta cells. Interestingly, comparisons between nDNA and mtDNA damage show that nDNA is more sensitive to the effects of MMS treatment. However, both strains are able to repair the nDNA lesions, contrary to mtDNA repair, which is compromised in the apn1 Delta mutant strain. Therefore, although nDNA is more sensitive than mtDNA to the effects of MMS, deletion of APN1 has a stronger phenotype in mtDNA repair than in nDNA. These results highlight the prominent role of APN1 in the repair of environmentally induced mtDNA damage.