Institute of Cell and Molecular Science

Background: Human papillomavirus (HPV), the causal agent of cervical cancer, appears to be involved in the etiology of cancer of the oral cavity and oropharynx. To investigate these associations, we conducted a multicenter case-control study of cancer of the oral cavity and oropharynx in nine countries. Methods: We recruited 1670 case patients (1415 with cancer of the oral cavity and 255 with cancer of the oropharynx) and 1732 control subjects and obtained an interview, oral exfoliated cells, and blood from all participants and fresh biopsy specimens from case patients. HPV DNA was detected by polymerase chain reaction (PCR). Antibodies against HPV16 L1, E6, and E7 proteins in plasma were detected with enzyme-linked immunosorbent assays. Multivariable models were used for case-control and casecase comparisons. Results: HPV DNA was detected in biopsy specimens of 3.9% (95% confidence interval [CI] ‫؍‬ 2.5% to 5.3%) of 766 cancers of the oral cavity with valid PCR results and 18.3% (95% CI ‫؍‬ 12.0% to 24.7%) of 142 cancers of the oropharynx (oropharynx and tonsil combined) with valid PCR results. HPV DNA in cancer biopsy specimens was detected less frequently among tobacco smokers and paan chewers and more frequently among subjects who reported more than one sexual partner or who practiced oral sex. HPV16 DNA was found in 94.7% of HPV DNA-positive case patients. HPV DNA in exfoliated cells was not associated with cancer risk or with HPV DNA detection in biopsy specimens. Antibodies against HPV16 L1 were associated with risk for cancers of the oral cavity (odds ratio [OR] ‫؍‬ 1.5, 95% CI ‫؍‬ 1.1 to 2.1) and the oropharynx (OR ‫؍‬ 3.5, 95% CI ‫؍‬ 2.1 to 5.9). Antibodies against HPV16 E6 or E7 were also associated with risk for cancers of the oral cavity (OR ‫؍‬ 2.9, 95% CI ‫؍‬ 1.7 to 4.8) and the oropharynx (OR ‫؍‬ 9.2, 95% CI ‫؍‬ 4.8 to 17.7). Conclusions: HPV appears to play an etiologic role in many cancers of the oropharynx and possibly a small subgroup of cancers of the oral cavity. The most common HPV type in genital cancers (HPV16) was also the most common in these tumors. The mechanism of transmission of HPV to the oral cavity warrants further investigation. [J Natl Cancer Inst 2003;95:

Context: Vitamin D deficiency, common in South Asians, is a risk factor for metabolic syndrome, type 2 diabetes, and ischemic heart disease. Vitamin D receptor (VDR) activation depends on activated vitamin D [1,25-dihydroxyvitamin D (1,25(OH) 2 D)] concentration, reflecting opposing actions of 25-hydroxyvitamin D-1␣-hydroxylase [1-␣(OH)ase] for formation and 25(OH)D-24-hydroxylase [24(OH)ase] for catabolism. We previously reported that circulating 1,25(OH) 2 D contributed to determination of VDR-protein levels and VDR genotype was a determinant of both VDR mRNA and VDR-protein in South Asians.

Background Several Type 1 diabetes susceptibility loci have been located to chromosome 2q12±21. However, results have not always been consistent and this may re¯ect study design and the population analysed. We have used a family-based design to look for an association between Type 1 diabetes and markers located to 2q12±21.

When a nerve axon is cut or crushed, the nerve fibers in the distal part of the axon, separated from the cell body, undergo a form of spontaneous degeneration, known as Wallerian degeneration. A substrain of the mouse inbred strain C57BL, known as C57BL/Ola, carries a mutant form of a gene involved in Wallerian degeneration in the peripheral and central nervous systems, and in retrograde degeneration of retinal ganglion cells. Wallerian degeneration in this substrain is abnormally slow. Previously the defect had been shown to be due to an autosomal dominant gene. The locus has been given the name and symbol Wallerian degeneration Wld, with the mutant allele WldS (Wallerian degeneration-slow). The Wld locus has now been mapped, by using conventional and molecular markers, to the distal end of chromosome 4, near the locus of pronatriodilatin (Pnd). The order of loci (with recombination distances in centimorgans, cM) is cen-D4Mitl-8.9 ± 1.7 cM-Fuca-2.5 ± 0.93 cM-Akp-2-3.2 ± 1.1 cM-WMit48-3.5 ± 1.1 cM-(Wld, Pnd, D4Mi49)-0.71 ± 0.50 cM-4Eno-1,

We report genetic aberrations that activate the ERK/MAP kinase pathway in 100% of posterior fossa pilocytic astrocytomas, with a high frequency of gene fusions between KIAA1549 and BRAF among these tumours. These fusions were identified from analysis of focal copy number gains at 7q34, detected using Affymetrix 250K and 6.0 SNP arrays. PCR and sequencing confirmed the presence of five KIAA1549–BRAF fusion variants, along with a single fusion between SRGAP3 and RAF1. The resulting fusion genes lack the auto-inhibitory domains of BRAF and RAF1, which are replaced in-frame by the beginning of KIAA1549 and SRGAP3, respectively, conferring constitutive kinase activity. An activating mutation of KRAS was identified in the single pilocytic astrocytoma without a BRAF or RAF1 fusion. Further fusions and activating mutations in BRAF were identified in 28% of grade II astrocytomas, highlighting the importance of the ERK/MAP kinase pathway in the development of paediatric low-grade gliomas. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The purpose of this study was to evaluate COX-2 mRNA expression with known clinical prognostic features of breast cancer, oestrogen/progesterone receptor status, tumour size and grade.Total RNA was extracted from 45 frozen breast tumour (invasive) and 22 normal breast tissue samples. COX-2 mRNA transcription was quantified using a real time RT-PCR assay and expressed as copy number/μg total RNA. All specimens were assessed for tumour grade, size, nodal status and presence of vascular invasion and oestrogen and progesterone receptor status.COX-2 mRNA was detected in all samples with a median copy number of 1.15 × 107 for tumours and 6.5 × 106 for normal samples. Expression was significantly higher in oestrogen receptor negative tumours compared to the receptor positive group. There was no correlation between COX-2 mRNA levels and tumour size, grade, nodal status and presence of vascular invasion.COX-2 mRNA expression is increased in oestrogen and progesterone receptor negative breast cancers.