Cancer Epidemiol Biomarkers Prev
June 2011
Background: TGF-β acts as a suppressor of primary tumor initiation but has been implicated as a promoter of the later malignant stages. Here associations with risk of invasive breast cancer are assessed for single-nucleotide polymorphisms (SNP) tagging 17 genes in the canonical TGF-β ALK5/SMADs 2&3 and ALK1/SMADs 1&5 signaling pathways: LTBP1, LTBP2, LTBP4, TGFB1, TGFB2, TGFB3, TGFBR1(ALK5), ALK1, TGFBR2, Endoglin, SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6, and SMAD7 [Approved Human Gene Nomenclature Committee gene names: ACVRL1 (for ALK1) and ENG (for Endoglin)].
Methods: Three-hundred-fifty-four tag SNPs (minor allele frequency > 0.
Introduction: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls.
View Article and Find Full Text PDFBackground: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI=1.0-1.
View Article and Find Full Text PDFOverweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2).
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
April 2011
Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.
View Article and Find Full Text PDFIdentification of somatic mutations in cancer is a major goal for understanding and monitoring the events related to cancer initiation and progression. High resolution melting (HRM) curve analysis represents a fast, post-PCR high-throughput method for scanning somatic sequence alterations in target genes. The aim of this study was to assess the sensitivity and specificity of HRM analysis for tumor mutation screening in a range of tumor samples, which included 216 frozen pediatric small rounded blue-cell tumors as well as 180 paraffin-embedded tumors from breast, endometrial and ovarian cancers (60 of each).
View Article and Find Full Text PDFBackground: Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA).
Methods: Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection.
Introduction: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium.
Methods: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314).
Background: Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.
Methods: We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies.
We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance.
View Article and Find Full Text PDFOver recent years, genome-wide association studies have contributed to our understanding of genetic susceptibility to sporadic cancer. In this study, we assessed the association between upper gastrointestinal cancer risk and four genome-wide association studies-identified single nucleotide polymorphisms (SNPs), implicated earlier in prostate and colorectal cancer susceptibility. Genotyping for each SNP was performed in two independent Caucasian population-based case-control studies.
View Article and Find Full Text PDFObjective: We assessed whether common genetic variation in PTEN, PIK3CA, AKT1, MLH1, and MSH2-genes that reportedly are frequently altered in endometrial cancer-was associated with risk of endometrial cancer.
Methods: Using data from a population-based case-control study in Poland (PECS) of 417 cases and 407 matched controls, we genotyped 76 tagging single nucleotide polymorphisms (tagSNPs; located in or within 10 kb upstream or 5 kb downstream of the gene of interest, minor allele frequency >=5% among various ethnic groups, and not already represented by another tagSNP at a LD of r(2) >=0.80) on an Illumina Custom Infinium iSelect assay that included over 29,000 SNPs in 1316 genes.
Objective: To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival.
Methods: The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival.
Background & Aims: An association between gastric cancer and the rs2294008 (C>T) polymorphism in the prostate stem cell antigen (PSCA) gene has been reported for several Asian populations. We set out to determine whether such an association exists in white individuals.
Methods: We genotyped 166 relatives of gastric cancer patients, including 43 Helicobacter pylori-infected subjects with hypochlorhydria and gastric atrophy, 65 infected subjects without these abnormalities, 58 H pylori-negative relatives, and 100 population controls.
Rationale: Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships.
Objectives: Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders.
Epithelial ovarian cancer (EOC) is the leading cause of death from gynecological malignancy in the developed world, accounting for 4% of the deaths from cancer in women. We performed a three-phase genome-wide association study of EOC survival in 8,951 individuals with EOC (cases) with available survival time data and a parallel association analysis of EOC susceptibility. Two SNPs at 19p13.
View Article and Find Full Text PDFOvarian cancer accounts for more deaths than all other gynecological cancers combined. To identify common low-penetrance ovarian cancer susceptibility genes, we conducted a genome-wide association study of 507,094 SNPs in 1,768 individuals with ovarian cancer (cases) and 2,354 controls, with follow up of 21,955 SNPs in 4,162 cases and 4,810 controls, leading to the identification of a confirmed susceptibility locus at 9p22 (in BNC2). Here, we report on nine additional candidate loci (defined as having P ≤ 10⁻⁴) identified after stratifying cases by histology, which we genotyped in an additional 4,353 cases and 6,021 controls.
View Article and Find Full Text PDFBackground: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals.
View Article and Find Full Text PDFBackground: Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A).
Objectives: We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk.
Cancer Epidemiol Biomarkers Prev
September 2010
Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious.
Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.
We hypothesized that variants in genes expressed as a consequence of interactions between ovarian cancer cells and the host micro-environment could contribute to cancer susceptibility. We therefore used a two-stage approach to evaluate common single nucleotide polymorphisms (SNPs) in 173 genes involved in stromal epithelial interactions in the Ovarian Cancer Association Consortium (OCAC). In the discovery stage, cases with epithelial ovarian cancer (n=675) and controls (n=1,162) were genotyped at 1,536 SNPs using an Illumina GoldenGate assay.
View Article and Find Full Text PDFPLoS Med
May 2010
Background: Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate mortality for patients with the major subtypes of breast cancer as classified using five immunohistochemical markers, to investigate patterns of mortality over time, and to test for heterogeneity by subtype.
Methods And Findings: We pooled data from more than 10,000 cases of invasive breast cancer from 12 studies that had collected information on hormone receptor status, human epidermal growth factor receptor-2 (HER2) status, and at least one basal marker (cytokeratin [CK]5/6 or epidermal growth factor receptor [EGFR]) together with survival time data.
Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases.
View Article and Find Full Text PDFBackground: Increased risk of renal cell carcinoma (RCC) with milk consumption has been reported from observational studies. Whether this represents a causal association or is a result of confounding or bias is unclear. We assessed the potential for using genetic variation in lactase persistence as a tool for the study of this relationship.
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