Correlation between rubella antibody levels and cytokine measures of cell-mediated immunity.

Despite a safe and effective vaccine, endemic rubella remains a problem in developing countries. Isolated cases and outbreaks can occur in areas with high vaccine coverage. Individuals, especially pregnant women who remain unimmunized or do not seroconvert, are susceptible to infection and their infants are at risk for congenital rubella syndrome (CRS).

Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes.

Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11-19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers.

Effect of human leukocyte antigen homozygosity on rubella vaccine-induced humoral and cell-mediated immune responses.

Human leukocyte antigen (HLA) genes play a critical role in host immunity, including vaccine responses. HLA molecules present antigenic peptides to T cells and provide inhibitory signals to NK cells, and polymorphisms within HLA genes allow binding and presentation of a diverse array of self and foreign peptides. Heterozygosity across HLA alleles has been found to play a positive role in host defense for a variety of infections.

Novel breast tissue feature strongly associated with risk of breast cancer.

Purpose: Accurate, individualized risk prediction for breast cancer is lacking. Tissue-based features may help to stratify women into different risk levels. Breast lobules are the anatomic sites of origin of breast cancer.

Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia.

Uncontrolled proliferation is a defining feature of the malignant phenotype. Ki67 is a marker for proliferating cells and is overexpressed in many breast cancers. Atypical hyperplasia is a premalignant lesion of the breast (relative risk approximately 4.

Replication of rubella vaccine population genetic studies: validation of HLA genotype and humoral response associations.

Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12-18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11-19 years (2nd cohort), all having had two doses of a rubella-containing vaccine.

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.

Background: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide.

Methods: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay.

Antioxidant intake from fruits, vegetables and other sources and risk of non-Hodgkin's lymphoma: the Iowa Women's Health Study.

Antioxidant nutrients found in fruits, vegetables and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of non-Hodgkin's lymphoma (NHL) overall and for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55-69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semiquantitative food frequency questionnaire.

A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs.

Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer.

Background: The nuclear factor-kappaB (NF-kappaB) family is a set of transcription factors with key roles in the induction of the inflammatory response and may be the link between inflammation and cancer development. This pathway has been shown to influence ovarian epithelial tissue repair. Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded.

Polymorphisms in the FGF2 gene and risk of serous ovarian cancer: results from the ovarian cancer association consortium.

Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumor progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesized that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analyzed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia.

Genetic variation in the chromosome 17q23 amplicon and breast cancer risk.

Background: Gene amplification leading to overexpression is a common event in breast tumors that is linked to tumor development and progression. The 17q23 region is amplified in >40% of breast tumors and contains several candidate oncogenes. Because common genetic variation in several oncogenes has been associated with cancer risk, we assessed the relevance of common variants in the 17q23 candidate oncogenes to breast cancer.

Polymorphisms in TCEAL7 and risk of epithelial ovarian cancer.

Objective: We have previously shown that TCEAL7 (transcription elongation factor A (SII)-like 7) is epigenetically down-regulated in the majority of epithelial ovarian cancers. We now examine the hypothesis that inherited alterations in TCEAL7 play a role in the etiology of ovarian cancer.

Methods: A two-site case-control study of 930 cases of ovarian cancer and 1037 controls, frequency-matched on residence, age and race, was conducted.

Association of genetic variation in mitotic kinases with breast cancer risk.

An RNAi-based functional screening of mitotic kinases in Drosophila recently identified a number of members of the kinome that are required for normal cell division. Depletion of these kinases resulted in a number of different mitotic abnormalities including spindle malformation, chromosome mis-segregation, centrosome amplification and failure of cytokinesis (Bettencourt-Dias et al. in Nature 432:980-987, 2004).

Variation in genes required for normal mitosis and risk of breast cancer.

The down-regulation of genes involved in normal cell division can cause aberrant mitoses and increased cell death. Surviving cells exhibit aneuploidy and/or polyploidy. Since mitotic disruption has been linked with tumor development and progression, alterations in the expression or activity of these mitotic regulators may contribute to breast tumor formation.

Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study.

Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer.

The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC).

Racial differences in primary central nervous system lymphoma incidence and survival rates.

To determine racial and ethnic differences in incidence and survival in patients with primary central nervous system lymphoma (PCNSL), NCI Surveillance, Epidemiology, and End Results (SEER) program data from 1992 to 2002 were queried. Data were substratified by age (20-49 years vs. 50 or above) and race (White, Black, Asian/Pacific Islander [A/PI], American Indian/Alaskan Native [AI/AN]).

Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk.

Polymorphisms in genes critical to cell cycle control are outstanding candidates for association with ovarian cancer risk; numerous genes have been interrogated by multiple research groups using differing tagging single-nucleotide polymorphism (SNP) sets. To maximize information gleaned from existing genotype data, we conducted a combined analysis of five independent studies of invasive epithelial ovarian cancer. Up to 2,120 cases and 3,382 controls were genotyped in the course of two collaborations at a variety of SNPs in 11 cell cycle genes (CDKN2C, CDKN1A, CCND3, CCND1, CCND2, CDKN1B, CDK2, CDK4, RB1, CDKN2D, and CCNE1) and one gene region (CDKN2A-CDKN2B).

Influence of host genetic variation on rubella-specific T cell cytokine responses following rubella vaccination.

The variability of immune response modulated by immune response gene polymorphisms is a significant factor in the protective effect of vaccines. We studied the association between cellular (cytokine) immunity and HLA genes among 738 schoolchildren (396 males and 342 females) between the ages of 11 and 19 years, who received two doses of rubella vaccine (Merck). Cytokine secretion levels in response to rubella virus stimulation were determined in PBMC cultures by ELISA.

HLA haplotype and supertype associations with cellular immune responses and cytokine production in healthy children after rubella vaccine.

Secreted rubella virus-specific cytokines reflect the immunologic mechanisms underlying adoptive immune responses and are significant markers of immunity to rubella. We studied the association between measures of cellular (cytokine and frequency of cytokine-secreted cells) immune responses and HLA haplotypes (with frequencies of > or =1%) and supertypes among 738 healthy children following two doses of rubella vaccine. Haplotype effects were estimated while accounting for linkage phase ambiguity via an expectation maximization algorithm.

Gender effects on humoral immune responses to smallpox vaccine.

There are no data currently available on gender and racial variation in smallpox vaccine immune responses. We recruited 1076 healthy adults 18-40 years old who received one dose of the US-licensed smallpox vaccine (Dryvax). Vaccinia neutralizing antibody titers in each subject's serum were determined using a high throughput neutralization assay based on a recombinant, beta-gal expressing vaccinia virus.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.

Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women.

Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.