RESUMO
Introduction: Diverting ostomy is a commonly perfomed procedure but may be associated to its own morbidity (early or late complications). Colostomy-related evisceration is a rare but potentially life threatening condition (requiring emergency surgery), relatively undocumented for its mechanisms. Case report: A male aged 84 was admited for chronic low digestive occlusion due to a locally advanced, stenosing, rectal adenocarcinoma. Prior to neoadjuvant therapy, a loop sigmoidostomy was indicated using a left iliac open aproach, with no preparation of the colic content. The sigmoid was loaded with hard stools. The parietal breach was reaproximated by 2 monofilament nylon sutures, fascial and colocutaneus fixation. Colostomy was opened two days later, but was not functional (postoperative paralytic ileus). Parastomal evisceration of ileum in day 3, dehiscence of parietal suture. Emergency operation, using the same aproach. Results: Favourable outcome. Thoraco-abdominal CT scan: N0,M0. Pelvic MRI: proliferative mass of inferior and middle rectum, involving mesorectum fascia, levator ani and a few regional lymphatic nodes. Radio-chemotherapy and abdomino-perineal resection. Pathologic result: colorectal adenocarcinoma, G2, ypT1ypN0, ICD-O: 8140/3. Conclusions: We rewiewed 8 case reports published since 2011, equally distributed as late or early complications. There was no connection with the princeps indication (colorectal cancer in half of cases); neither related to topography (transverse or sigmoid) or type of colostomy (loop or end). Occurence of the complication is not time-dependent (5 to18 months in late, 3 to 12 days for early eviscerations). The main premise is colostomy itself (a place of reduced parieto-abdominal resistence), stressed by increassed intra-abdominal pressure (eg. bronchopulmonary disease, digestive obstruction). Predisposing factors for late evisceration seems to be related to spontaneous rupture of parastomal hernia/colostomy prolapse. As for early evisceration, both technical details and surgical strategy must be considered (indequate fixation; creation of a larger than necessary colostomy aperture).
Assuntos
Adenocarcinoma/cirurgia , Colostomia/efeitos adversos , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Obstrução Intestinal/cirurgia , Neoplasias Retais/cirurgia , Adenocarcinoma/complicações , Adenocarcinoma/diagnóstico por imagem , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante , Hérnia Ventral/etiologia , Humanos , Hérnia Incisional/etiologia , Obstrução Intestinal/etiologia , Pseudo-Obstrução Intestinal/etiologia , Masculino , Protectomia , Neoplasias Retais/complicações , Neoplasias Retais/diagnóstico por imagem , Deiscência da Ferida Operatória/etiologia , Deiscência da Ferida Operatória/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).
Assuntos
Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA/genética , Predisposição Genética para Doença , Polipose Adenomatosa do Colo/epidemiologia , Polipose Adenomatosa do Colo/patologia , Adulto , Idoso , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , DNA Glicosilases/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Mutação , Fatores de Risco , Romênia/epidemiologiaRESUMO
High-risk mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas cutaneous types (e.g. HPV8 and 77) are suspected to be involved in non-melanoma skin cancer. The antibody response to HPVs is a key determinant of protective immunity, but not all infected individuals seroconvert. Genetic variability of the host may have large impact on seroconversion. A previous genome-wide association study (GWAS) has identified a susceptibility locus (rs41270488) for HPV8 seropositivity within the major histocompatibility complex (MHC) region. To further study this locus, we imputed alleles at classical leukocyte antigen (HLA) loci using HLA*IMP:02 with a reference panel from the HapMap Project and the 1958 Birth Cohort, and conducted an integrated analysis among 4811 central European subjects to assess the contribution of classical HLA alleles and gene copy number variation (CNV) at the hypervariable DRB locus within the MHC region to HPV seropositivity at both the individual HPV type level and the phylogenetic species level. Our study provides evidence that the association noted between rs41270488 and HPV8 seropositivity is driven by two independent variants, namely DQB1*0301 [odds ratio (OR) = 1.51, 95% confidence interval (CI) = 1.36-1.68, P = 1.0 × 10(-14)] and DRB1*1101 (OR = 1.89, 95%CI = 1.57-2.28, P = 1.5 × 10(-11)) within the HLA class II region. Additionally, we identified two correlated alleles DRB1*0701 (OR = 1.67, 95%CI = 1.41-1.98, P = 2.6 × 10(-9)) and DQA1*0201 (OR = 1.67, 95%CI = 1.38-1.93, P = 1.7 × 10(-8)), to be associated with HPV77 seropositivity. Comparable results were observed through imputation using SNP2HLA with another reference panel from the Type 1 diabetes Genetics Consortium. This study provides support for an important role of HLA class II alleles in antibody response to HPV infection.
Assuntos
Alelos , Predisposição Genética para Doença , Variação Genética , Complexo Principal de Histocompatibilidade/genética , Infecções por Papillomavirus/genética , Estudos de Casos e Controles , Feminino , Antígenos HLA/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Razão de Chances , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/genética , Neoplasias da Próstata/genética , Alelos , Estudos de Casos e Controles , Genoma Humano , Estudo de Associação Genômica Ampla , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Fatores de Risco , RomêniaRESUMO
Dedifferentiated liposarcoma is a liposarcoma that contains a well-differentiated liposarcoma component juxtaposed to areas of high-grade non-lipogenic sarcoma and was believed to occur from well-differentiated liposarcoma after several years. Dedifferentiated liposarcoma most commonly occurs in the retroperitoneum, while an intraperitoneal location is extremely rare, only seven cases have been reported in literature. Many pathologists recognize that a large number of intra-abdominal poorly differentiated sarcomas are dedifferentiated liposarcomas. We present the case of a 73 years old patient known with multiple cardiovascular comorbidities, stroke sequelae and a large abdominal mass evolving for 3 years. He was referred to our clinic for abdominal pain and bowel disorders. Instead of all clinical and imagistic aspects suggested a gastrointestinal stromal tumour, the histological exam revealed the diagnosis of a dedifferentiated liposarcoma.
Assuntos
Lipossarcoma/patologia , Neoplasias do Colo Sigmoide/patologia , Idoso , Colectomia , Humanos , Lipossarcoma/cirurgia , Masculino , Fatores de Risco , Neoplasias do Colo Sigmoide/cirurgia , Resultado do TratamentoRESUMO
Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.
Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Fumar/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Adulto JovemRESUMO
High-risk α mucosal types of human papillomavirus (HPV) cause anogenital and oropharyngeal cancers, whereas ß cutaneous HPV types (e.g. HPV8) have been implicated in non-melanoma skin cancer. Although antibodies against the capsid protein L1 of HPV are considered as markers of cumulative exposure, not all infected persons seroconvert. To identify common genetic variants that influence HPV seroconversion, we performed a two-stage genome-wide association study. Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European case-control study of lung, head and neck and kidney cancer that had serology data available on 13 HPV types. Only one association met genome-wide significance criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR) = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 × 10(-10)], a common genetic variant (minor allele frequency=0.33) located within the major histocompatibility complex (MHC) II region at 6p21.32. This association was subsequently replicated in an independent set of 2344 subjects from a Latin American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56, P=2.2 × 10(-5)), yielding P=1.3 × 10(-14) in the combined analysis (P-heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung cancer cases/head and neck cancer cases/kidney cancer cases). This study provides a proof of principle that genetic variation plays a role in antibody reactivity to HPV infection.
Assuntos
Estudo de Associação Genômica Ampla , Soropositividade para HIV/genética , Anticorpos Anti-HIV/imunologia , Soropositividade para HIV/imunologia , Humanos , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , População Branca/genéticaRESUMO
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. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Índice de Massa Corporal , Neoplasias Laríngeas/etiologia , Neoplasias Bucais/etiologia , Neoplasias Faríngeas/etiologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Humanos , Razão de Chances , Fatores de RiscoRESUMO
Although cigarette smoking and alcohol consumption increase risk for head and neck cancers, there have been few attempts to model risks quantitatively and to formally evaluate cancer site-specific risks. The authors pooled data from 15 case-control studies and modeled the excess odds ratio (EOR) to assess risk by total exposure (pack-years and drink-years) and its modification by exposure rate (cigarettes/day and drinks/day). The smoking analysis included 1,761 laryngeal, 2,453 pharyngeal, and 1,990 oral cavity cancers, and the alcohol analysis included 2,551 laryngeal, 3,693 pharyngeal, and 3,116 oval cavity cancers, with over 8,000 controls. Above 15 cigarettes/day, the EOR/pack-year decreased with increasing cigarettes/day, suggesting that greater cigarettes/day for a shorter duration was less deleterious than fewer cigarettes/day for a longer duration. Estimates of EOR/pack-year were homogeneous across sites, while the effects of cigarettes/day varied, indicating that the greater laryngeal cancer risk derived from differential cigarettes/day effects and not pack-years. EOR/drink-year estimates increased through 10 drinks/day, suggesting that greater drinks/day for a shorter duration was more deleterious than fewer drinks/day for a longer duration. Above 10 drinks/day, data were limited. EOR/drink-year estimates varied by site, while drinks/day effects were homogeneous, indicating that the greater pharyngeal/oral cavity cancer risk with alcohol consumption derived from the differential effects of drink-years and not drinks/day.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Neoplasias de Cabeça e Pescoço/etiologia , Fumar/efeitos adversos , Estudos de Casos e Controles , Humanos , Neoplasias Laríngeas/etiologia , Neoplasias Bucais/etiologia , Razão de Chances , Neoplasias Faríngeas/etiologia , Fatores de RiscoRESUMO
The authors pooled data from 15 case-control studies of head and neck cancer (9,107 cases, 14,219 controls) to investigate the independent associations with consumption of beer, wine, and liquor. In particular, they calculated associations with different measures of beverage consumption separately for subjects who drank beer only (858 cases, 986 controls), for liquor-only drinkers (499 cases, 527 controls), and for wine-only drinkers (1,021 cases, 2,460 controls), with alcohol never drinkers (1,124 cases, 3,487 controls) used as a common reference group. The authors observed similar associations with ethanol-standardized consumption frequency for beer-only drinkers (odds ratios (ORs) = 1.6, 1.9, 2.2, and 5.4 for < or =5, 6-15, 16-30, and >30 drinks per week, respectively; P(trend) < 0.0001) and liquor-only drinkers (ORs = 1.6, 1.5, 2.3, and 3.6; P < 0.0001). Among wine-only drinkers, the odds ratios for moderate levels of consumption frequency approached the null, whereas those for higher consumption levels were comparable to those of drinkers of other beverage types (ORs = 1.1, 1.2, 1.9, and 6.3; P < 0.0001). Study findings suggest that the relative risks of head and neck cancer for beer and liquor are comparable. The authors observed weaker associations with moderate wine consumption, although they cannot rule out confounding from diet and other lifestyle factors as an explanation for this finding. Given the presence of heterogeneity in study-specific results, their findings should be interpreted with caution.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Bebidas Alcoólicas/efeitos adversos , Etanol/efeitos adversos , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Cerveja/efeitos adversos , Estudos de Casos e Controles , Neoplasias de Cabeça e Pescoço/induzido quimicamente , Humanos , Razão de Chances , Medição de Risco , Fatores de Risco , Vinho/efeitos adversosRESUMO
With the aim to dissect the effect of adult height on head and neck cancer (HNC), we use the Mendelian randomization (MR) approach to test the association between genetic instruments for height and the risk of HNC. 599 single nucleotide polymorphisms (SNPs) were identified as genetic instruments for height, accounting for 16% of the phenotypic variation. Genetic data concerning HNC cases and controls were obtained from a genome-wide association study. Summary statistics for genetic association were used in complementary MR approaches: the weighted genetic risk score (GRS) and the inverse-variance weighted (IVW). MR-Egger regression was used for sensitivity analysis and pleiotropy evaluation. From the GRS analysis, one standard deviation (SD) higher height (6.9 cm; due to genetic predisposition across 599 SNPs) raised the risk for HNC (Odds ratio (OR), 1.14; 95% Confidence Interval (95%CI), 0.99-1.32). The association analyses with potential confounders revealed that the GRS was associated with tobacco smoking (OR = 0.80, 95% CI (0.69-0.93)). MR-Egger regression did not provide evidence of overall directional pleiotropy. Our study indicates that height is potentially associated with HNC risk. However, the reported risk could be underestimated since, at the genetic level, height emerged to be inversely associated with smoking.
Assuntos
Estatura/genética , Neoplasias de Cabeça e Pescoço/genética , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.
Assuntos
Proteína BRCA2/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
Genetic variants located within the 12p13.33/RAD52 locus have been associated with lung squamous cell carcinoma (LUSC). Here, within 5,947 UADT cancers and 7,789 controls from 9 different studies, we found rs10849605, a common intronic variant in RAD52, to be also associated with upper aerodigestive tract (UADT) squamous cell carcinoma cases (OR = 1.09, 95% CI: 1.04-1.15, p = 6x10(-4)). We additionally identified rs10849605 as a RAD52 cis-eQTL inUADT(p = 1x10(-3)) and LUSC (p = 9x10(-4)) tumours, with the UADT/LUSC risk allele correlated with increased RAD52 expression levels. The 12p13.33 locus, encompassing rs10849605/RAD52, was identified as a significant somatic focal copy number amplification in UADT(n = 374, q-value = 0.075) and LUSC (n = 464, q-value = 0.007) tumors and correlated with higher RAD52 tumor expression levels (p = 6x10(-48) and p = 3x10(-29) in UADT and LUSC, respectively). In combination, these results implicate increased RAD52 expression in both genetic susceptibility and tumorigenesis of UADT and LUSC tumors.
Assuntos
Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 12/genética , Loci Gênicos , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/genética , Proteína Rad52 de Recombinação e Reparo de DNA/genética , Estudos de Casos e Controles , Simulação por Computador , Demografia , Feminino , Células Germinativas , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mapeamento Físico do Cromossomo , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Fatores de RiscoRESUMO
BACKGROUND AND AIM: Colon tumor carcinogenesis and rectal tumor carcinogenesis have each been associated with different genetic features, but data are still controversial and are insufficient to support their distinct molecular biology. Recently, genome-wide association studies (GWAS) have also found heterogeneity in colorectal cancer (CRC) risks based on population ethnicity and tumor features. Several single nucleotide polymorphism (SNP) markers are described in the literature as having site and/or stage specificity, including rs10795668, rs3802842, rs6983267, and rs4939827. Replication of initial findings in different ethnic groups by independent studies is required to unravel the population-specific differences in risk. METHODS: We examined whether inherited risk variants at rs10795668, rs3802842, rs6983267, and rs4939827 exerted a differential effect on colon and rectal cancers in a Romanian hospital based series of 153 CRC cases and 182 non-affected control subjects prospectively recruited between 2007 and 2010. RESULTS: Rectal tumors were significantly associated with rs4939827 (OR = 4.85, P = 0.002) and rs6983267 (OR = 3.00, P = 0.036), suggesting that carriers of risk alleles at these loci had increased susceptibility to development of rectal cancer rather than colon cancer. Carrying the C allele at rs3802842 appeared to be associated with a lower risk for rectal tumors in our dataset. We found no association between genotypes and tumor aggressiveness as reflected by TNM staging. CONCLUSIONS: The associations between SNPs, and tumor site and staging remain to be further clarified. Our results should be considered cautiously, but may be taken into account in future, larger epidemiological studies.
Assuntos
Neoplasias Colorretais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Técnicas de Genotipagem , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Risco , RomêniaRESUMO
BACKGROUND: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. METHODS: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest--the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. RESULTS: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)]â=â2.5×10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. CONCLUSION: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).
Assuntos
Cromossomos Humanos Par 4 , Biologia Computacional/métodos , Estudo de Associação Genômica Ampla , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Teorema de Bayes , Predisposição Genética para Doença , Humanos , Internet , Neoplasias Pulmonares/genética , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Quitting tobacco or alcohol use has been reported to reduce the head and neck cancer risk in previous studies. However, it is unclear how many years must pass following cessation of these habits before the risk is reduced, and whether the risk ultimately declines to the level of never smokers or never drinkers. METHODS: We pooled individual-level data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium. Data were available from 13 studies on drinking cessation (9167 cases and 12 593 controls), and from 17 studies on smoking cessation (12 040 cases and 16 884 controls). We estimated the effect of quitting smoking and drinking on the risk of head and neck cancer and its subsites, by calculating odds ratios (ORs) using logistic regression models. RESULTS: Quitting tobacco smoking for 1-4 years resulted in a head and neck cancer risk reduction [OR 0.70, confidence interval (CI) 0.61-0.81 compared with current smoking], with the risk reduction due to smoking cessation after > or =20 years (OR 0.23, CI 0.18-0.31), reaching the level of never smokers. For alcohol use, a beneficial effect on the risk of head and neck cancer was only observed after > or =20 years of quitting (OR 0.60, CI 0.40-0.89 compared with current drinking), reaching the level of never drinkers. CONCLUSIONS: Our results support that cessation of tobacco smoking and cessation of alcohol drinking protect against the development of head and neck cancer.
Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Comportamento de Redução do Risco , Fatores Sexuais , Fatores Socioeconômicos , Fatores de TempoRESUMO
Alcohol is an important risk factor for upper aerodigestive cancers and is principally metabolized by alcohol dehydrogenase (ADH) enzymes. We have investigated six ADH genetic variants in over 3,800 aerodigestive cancer cases and 5,200 controls from three individual studies. Gene variants rs1229984 (ADH1B) and rs1573496 (ADH7) were significantly protective against aerodigestive cancer in each individual study and overall (P = 10(-10) and 10(-9), respectively). These effects became more apparent with increasing alcohol consumption (P for trend = 0.0002 and 0.065, respectively). Both gene effects were independent of each other, implying that multiple ADH genes may be involved in upper aerodigestive cancer etiology.
Assuntos
Álcool Desidrogenase/genética , Transtornos Induzidos por Álcool/genética , Neoplasias Esofágicas/genética , Neoplasias Laríngeas/genética , Neoplasias Orofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Distribuição por Idade , Consumo de Bebidas Alcoólicas , Transtornos Induzidos por Álcool/epidemiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Laríngeas/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Orofaríngeas/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: The purpose of this study was to investigate the role of polymorphisms of genes involved in inflammation in the risk of cancers of the upper aerodigestive tract (UADT). METHODS: We have evaluated the role of polymorphisms in key genes related to inflammation, namely IL1B (rs1143627), COX2/PTGS2 (rs5275), and IL8 (rs4073) in a large case-control study comprising 811 UADT cancer cases and 1,083 controls. RESULTS: An association was observed for squamous cell carcinoma of the pharynx for a polymorphism in the promoter of the IL1B gene, with an OR of 2.39 (95% CI = 1.19-4.81) for the homozygotes for the minor allele A promoter polymorphism of IL8 was associated with decreased risk of laryngeal cancer, with an OR of 0.70 (95% CI = 0.50-0.98) for carriers of the minor allele. CONCLUSIONS: To our knowledge, this is the first report on the role of these polymorphisms with respect to UADT carcinogenesis. Our results suggest that inflammation-related polymorphisms play a role, albeit minor, in the risk of developing cancers of the upper aerodigestive tract.