Lung cancer and smoking: molecular aspects

Lung cancer (LC) is characterized as one of the most common and lethal types of cancers worldwide, with approximately 230.000 new cases each year in the US and 160.000 deaths are estimated for 2012. In Brazil, the outlook is also bleak, with 27,320 new cases expected in 2012, according to the Brazilian National Cancer Institute (INCA). LC is classified into two major histological types: small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). In addition to sizable mortality and incidence, LC has low 5-year survival rates when compared to other types of common cancers such as breast and prostate, even with recent diagnostic and therapeutic advances. For the survival rate of patients with LC to increase, a greater understanding of the molecular events that lead to the emergence of this malignancy is necessary in order to identify genetic markers involved in tumor progression, and thus enable early detection and to develop new specific therapeutic strategies, allowing for a more individualized treatment in patients with LC. Different situations are classified as risk factors for the development of LC, but unquestionably, the most responsible risk factor for the high incidence of LC in the world population by far is smoking.

Evaluation of PvuII and XbaI polymorphisms in the estrogen receptor alpha gene (ESR1) in relation to menstrual cycle timing and reproductive parameters in post-menopausal women.

OBJECTIVE: To evaluate the association of -397T>C and -351A>G single nucleotide polymorphisms (SNPs) - also called PvuII and XbaI, respectively - located on estrogen receptor alpha (ERS1) gene with age at menarche, menopause onset, fertility and miscarriage in a population of post-menopausal women. STUDY DESIGN: Cross-sectional study with 273 healthy, high miscegenated, post-menopausal women (mean age of 63.1±9.7 years old). Subjects were genotyped for PvuII and XbaI SNPs by PCR-RFLP and confirmed by automatic sequencing. Reproduction informations (age at menarche, age at menopause, number of pregnancies, fertility rate and miscarriages) were obtained by retrospective study using a questionnaire. RESULT(S): Age at menarche, menopause onset, number of pregnancies, total fertility rate, and parity did not seem to be influenced by any of the studied genotypes (chi-square, p>0.05). However, women carrying the xx genotype showed a 44% higher chance of miscarriage, whereas this value did not trespass 16% for any other genotype analyzed. It has been also observed a higher occurrence of miscarriage in association with combined xxpp genotype of ERS1 gene (chi-square, p<0.01). CONCLUSION(S): The present data indicate that the studied SNPs on ERS1 gene do not influence the menstrual cycle timing and parity but there is a strong relationship between the xx ERS1 SNP genotype and the incidence of miscarriage in the post-menopausal population analyzed.

The Cotransporter NaPi-IIb: characteristics, regulation and its role in carcinogenesis

Inorganic phosphate (Pi) presents a crucial role in cellular metabolism, with the kidney and intestine as the principal regulating organs of the homeostasis of this nutrient. Maintaining phosphate balance results from the activity of different subtype of transporters of sodium-dependent phosphate that use the electrochemical gradient of sodium ions to carry out cotransport. Several diseases have been related to dysfunctions of phosphate cotransporters, including in the area of oncology. A study using the SAGE technique pointed to a possible role of the type IIb sodium-phosphate cotransporter (NaPi-IIb), encoded by the SLC34A2 gene, in ovarian carcinogenesis. More recently, such protein was associated with the development of other carcinomas and some of the components that regulate its function were determined. It is believed that in the future, the analysis of SLC34A2 expression in tumor samples will help in the choice of treatment, evaluation of prognosis and be a possible target for new therapeutic strategies.