ABSTRACT
In contrast to studies focused on cigarette smoking and risk of breast cancer occurrence, this study explored the influence of smoking on breast cancer recurrence and progression. The goal was to evaluate the interaction between smoking history and gene expression levels on recurrence and overall survival of breast cancer patients. Multivariable Cox proportional hazards models were fitted for 48 cigarette smokers, 50 non-smokers, and the total population separately to determine which gene expressions and gene expression/cigarette usage interaction terms were significant in predicting overall and disease-free survival in breast cancer patients. Using methods similar to Andres et al. (BMC Cancer 13:326, 2013a; Horm Cancer 4:208-221, 2013b), multivariable analyses revealed CENPN, CETN1, CYP1A1, IRF2, LECT2, and NCOA1 to be important predictors for both breast carcinoma recurrence and mortality among smokers. Additionally, COMT was important for recurrence, and NAT1 and RIPK1 were important for mortality. In contrast, only IRF2, CETN1, and CYP1A1 were significant for disease recurrence and mortality among non-smokers, with NAT2 additionally significant for survival. Analysis of interaction between smoking status and gene expression values using the combined samples revealed significant interactions between smoking status and CYP1A1, LECT2, and CETN1. Signatures consisting of 7-8 genes were highly predictive for breast cancer recurrence and overall survival among smokers, with median C-index values of 0.8 and 0.73 for overall survival and recurrence, respectively. In contrast, median C-index values for non-smokers was only 0.59. Hence, significant interactions between gene expression and smoking status can play a key role in predicting breast cancer patient outcomes.
Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/mortality , Gene Expression Regulation, Neoplastic , Smoking/adverse effects , Adult , Aged , Disease-Free Survival , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/genetics , Proportional Hazards Models , Smoking/genetics , Survival AnalysisABSTRACT
Adipokines are important for regulation body metabolism and immune response. Many studies have shown that variants in adipokines genes play a role in age-associated diseases. In this study, we investigated the contribution of rs266729 (-11377G/C), rs2241766 (+45T/G), and rs1501299 (+276 G/T) SNPs of adiponectin gene (ADIPQO) and rs7799039 (-2548C/A) SNP of leptin (LEP) gene to human longevity phenotype in Jordanian population. Polymorphisms were genotyped in 110 randomly selected elderly subjects (>85 years old) with mean age of 90.2 years, and 120 young control subjects (range from 20 to 50 years) with mean age of 32.0 years. No significant differences were detected in the genotype and allele frequencies of examined gene variants between the two groups (p > 0.05). However, when gender was considered, genotypes and alleles frequencies of rs1501299 SNP in ADIPOQ gene and rs7799039 in LEP gene were significantly associated with longevity in men (p < 0.02) but not in women (p > 0.05). Thus, ADIPOQ and LEP genes polymorphisms might play a gender-specific role in the pathway to men's longevity.
