RESUMO
Genetic factors associated with the risk of smoking related cancers have until recently remained elusive. Since the publication of a genome-wide association study (GWAS) on lung cancer new genetic loci have been identified that appear to be associated with disease risk. In this replication study we genotyped 14 single nucleotide polymorphisms (SNPs) located at the 5p12.3-p15.33, 6p21.3-p22.1, 6q23-q27 and 15q25.1 loci in 874 lung, 450 bladder, 418 laryngeal cancer cases and cancer-free controls, matched by year of birth and sex to the cases. Our results revealed that loci in the chromosome region 15q25.1 (rs16969968[A], rs8034191[G]) and 5p15 (rs402710[T]) are associated with lung cancer risk in the Polish population (smoking status adjusted OR = 1.45, 1.35, 0.77; p ≤ 0.0001, 0.0005, 0.002; 95%CI 1.23-1.72, 1.14-1.59, 0.66-0.91 respectively). None of the other regions analyzed herein were implicated in the risk of lung, bladder or laryngeal cancer. This study supports previous findings on lung cancer but fails to show association of SNPs located in 15q25.1 and 5p15 region with other smoking related cancers like bladder and laryngeal cancer.
Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 6 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Laríngeas/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Laríngeas/etiologia , Neoplasias Pulmonares/etiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polônia , Risco , Neoplasias da Bexiga Urinária/etiologiaRESUMO
In this report the contribution of CDKN2A/ARF germline mutations to early-onset cancers of the breast, pancreas and malignant melanoma was examined. We screened 66 women with breast cancer diagnosed at age 30 and below, 72 melanoma patients with the median age at diagnosis < or = 40 years and 51 pancreatic cancer patients diagnosed under the age of 50 years. In the total set of 189 patients we found a novel change Pro48Arg (nt 143 c > g), a novel intronic change IVS1+36 g>c and two common variants A148T and IVS3+29 c>g. The results of this study revealed a paucity of mutations in CDKN2A/ARF suggesting that in the Polish population this gene does not contribute significantly to early-onset breast cancer, pancreatic cancer and malignant melanoma.
Assuntos
Neoplasias da Mama/genética , Genes p16 , Melanoma/genética , Neoplasias Pancreáticas/genética , Adulto , Idade de Início , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/epidemiologia , Polônia/epidemiologia , Polimorfismo de Fragmento de Restrição , PrevalênciaRESUMO
Both breast and lung cancers are common malignancies and within the context of known genetic predispositions to breast cancer, no association has been made in linking the two diseases together. This does not exclude the possibility that such associations may exist that lie outside the known high-risk breast cancer families. To examine the likelihood of common genetic factors that could influence the risk of disease, two sets of consecutively collected tumor groups were examined for the 3020insC mutation in the NOD2/CARD15 gene. A total of 4107 consecutively collected breast cancer patients were assessed for the prevalence of the 3020insC mutation and compared to a consecutively collected series of 389 lung cancer patients and 2068 control samples. The results revealed that a proportion of breast cancer patients who had a first or a second degree relative diagnosed with lung cancer were more likely to harbour a change in NOD2/CARD15 compared to patients who had no relatives affected by lung cancer. Furthermore, this difference appeared to be specific to the breast and lung cancer subgroup since there was no difference in the frequency of the 3020insC allele in the consecutively collected lung cancer patients. In conclusion, it appears that the 3020insC mutation of the NOD2/CARD15 gene may be a genetic predisposing factor for aggregations of breast and lung cancer.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Mutação , Idade de Início , Alelos , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2 , PrevalênciaRESUMO
The population frequencies of the CDKN2A common variants remain undetermined. In Poland, there is a common variant of the CDKN2A: an alanine to threonine substitution (A148T), which has been detected in other populations. We have recently showed that it is significantly overrepresented among Polish melanoma patients when compared to general population. Herein, we ascertained the prevalence of the A148T variant in 3,583 unselected cancer cases and 3,000 random control subjects from the same Polish population. We evaluated eleven different malignancies, representing the majority of all common cancer sites. Positive association with A148T variant was observed for lung cancer (OR, 2.0; p = 0.0052). A similar trend, although nonsignificant after the Bonferroni correction, was observed for colorectal cancer (OR, 1.5; p = 0.5499). These results suggest that A148T variant may be associated with a multi-organ cancer risk in the Polish population.