Use of false cell lines remains a major problem in biological research. Short tandem repeat (STR) profiling represents the gold standard technique for cell line authentication. However, mismatch repair (MMR) deficient cell lines are characterized by microsatellite instability, which could force allelic drifts in combination with a selective outgrowth of otherwise persisting side lines, and thus, are likely to be misclassified by STR-profiling. Based on the high-throughput Luminex platform, we developed a 24-plex SNP-profiling assay, called Multiplex Cell Authentication (MCA), for determining authentication of human cell lines. MCA was evaluated by analysing a collection of 436 human cell lines from the DSMZ, previously characterised by eight loci STR profiling. Both assays showed a very high degree of concordance and similar average matching probabilities (~1 × 10−8 for STR-profiling and ~1 × 10−9 for MCA). MCA enabled the detection of less than 3% contaminating human cells. Analysing MMR deficient cell lines, evidence was obtained for a higher robustness of the MCA compared to STR profiling. In conclusion, MCA could complement routine cell line authentication and replace the standard authentication STR technique in case of MSI cell lines.

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

Gallstones and cholecystectomy may be related to digestive system cancer through inflammation, altered bile flux, and changes in metabolic hormone levels. Although gallstones are recognized causes of gallbladder cancer, associations with other cancers of the digestive system are poorly established. We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1992-2005), which includes 17 cancer registries that cover approximately 26% of the US population, to identify first primary cancers (n = 236,850) occurring in persons aged ≥66 years and 100,000 cancer-free population-based controls frequency-matched by calendar year, age, and gender. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis, adjusting for the matching factors. Gallstones and cholecystectomy were associated with increased risk of noncardia gastric cancer (odds ratio (OR) = 1.21 (95% confidence interval (CI): 1.11, 1.32) and OR = 1.26 (95% CI: 1.13, 1.40), respectively), small-intestine carcinoid (OR = 1.27 (95% CI: 1.01, 1.60) and OR = 1.78 (95% CI: 1.41, 2.25)), liver cancer (OR = 2.35 (95% CI: 2.18, 2.54) and OR = 1.26 (95% CI: 1.12, 1.41)), and pancreatic cancer (OR = 1.24 (95% CI: 1.16, 1.31) and OR = 1.23 (95% CI: 1.15, 1.33)). Colorectal cancer risk associated with gallstones and cholecystectomy decreased with increasing distance from the common bile duct (P-trend < 0.001). Hence, gallstones and cholecystectomy are associated with the risk of cancers occurring throughout the digestive tract.

Supplemental Digital Content is available in the text

No abstract

We evaluated incidence patterns of biliary tract cancers (gallbladder, extrahepatic bile duct, ampulla of Vater, and not otherwise specified) to provide potential insight into the etiology of these cancers. Data were obtained from the population-based Surveillance, Epidemiology, and End Results (SEER) program. Rates for cases diagnosed during 1992–2009 were calculated by racial/ethnic, gender, and age groups. Temporal trends during 1974–2009 and annual percentage changes (APC) during 1992–2009 were estimated. Age-adjusted rates by site were higher among American Indian/Alaska Natives, Hispanics (white) and Asian/Pacific Islanders (Asian/PI) and lower among whites and blacks. Gallbladder cancer was more common among women in all ethnic groups (female-to-male incidence rate ratio [IRR] ranged from 1.24 to 2.86), but bile duct and ampulla of Vater cancers were more common among men (female-to-male IRR 0.57 to 0.82). Gallbladder cancer rates declined among all racial/ethnic and gender groups except blacks (APC −0.4% to −3.9%). In contrast, extrahepatic bile duct cancer rates rose significantly in most female racial/ethnic groups; the APCs among whites were 0.8 among females and 1.3 among males, both significant. Rates for ampulla of Vater cancer decreased among Asian/PI females (APC −2.7%) but remained stable for the other groups. In addition to confirming that biliary tract cancer incidence patterns differ by gender and site, and that the gallbladder cancer incidence rates have been declining, this study provides novel evidence that extrahepatic bile duct cancer rates are rising. These observations may help guide future etiologic studies.

Numerous studies have found the presence of viral DNA in colorectal tumor tissues. However, whether viral infections contribute to the risk of colorectal cancer (CRC) is still under debate. We aimed to provide an overview of published epidemiological studies on the association between viral infections and CRC. A systematic literature search was performed in PubMed to find relevant studies published until 8 May 2014. Information collected included study population, sample type, laboratory method and prevalence of viral infection in cancer or precancer patients and controls. We found 41 studies that fulfilled the selection criteria, all of which had cross-sectional or case-control designs, and most of which were of small to moderate size. Viral infections included human papillomaviruses (HPV), human polyomaviruses, human herpesviruses, human bocavirus and InoueMelnick virus. Inconsistent results were observed across studies. Many studies reported higher viral DNA prevalence in tumor tissues than in normal noncancerous tissues either in the same patients or in CRC-free controls. However, potential contamination or temporal sequence of the infection and cancer development were often unclear. Seroprevalence studies assessing antibody titers indicative of viral infections did not find statistically significant differences between CRC cases and healthy controls. Overall published evidence on the role of viral infections in CRC etiology remains limited. Given the potential importance of viral infections and their implication for prevention, there is a strong need for large, methodologically rigorous epidemiological studies.

ObjectivesTo assess the association of H. pylori and chronic atrophic gastritis (AG) with colonic, pancreatic and gastric cancer in a population-based prospective cohort.MethodsSerum antibodies against H. pylori in general and specific to cytotoxin-associated gene A (CagA), as well as serum pepsinogen I and II were analyzed in 9,506 men and women, aged 50–75 years in a cohort study from Saarland, Germany. Incident cases of colonic, pancreatic and gastric cancer were ascertained by record linkage with data from the Saarland Cancer Registry.ResultsDuring an average follow-up of 10.6 years, 108 colonic, 46 pancreatic and 27 gastric incident cancers were recorded. There was no association between H. pylori infection and colonic cancer (HR = 1.07; 95% CI 0.73–1.56) or pancreatic cancer (HR = 1.32; 0.73–2.39), regardless of either CagA seropositivity or AG status. In contrast, CagA+ infection was associated with a strongly increased risk of gastric cancer, especially non-cardia gastric cancer, and this association was particularly pronounced in the presence of AG. Compared to people without AG and without CagA+ infection, people with both risk factors had a significantly increased risk of non-cardia gastric cancer (HR = 32.4; 7.6–137.6).ConclusionsThis large cohort study did not observe an association of H. pylori infection or AG with colonic or pancreatic cancer, but underlines that the vast majority of non-cardia gastric cancers arise from AG and infection with CagA+ H. pylori strains.