TY - JOUR 
A1 - Yvert, Thomas Paul
AU - Iana, C. I.
AU - Rubio Alonso, Margarita
AU - Gómez Gallego, Félix
AU - Santiago Dorrego, Catalina
T1 - Is the PPARGC1A RS 8192678 polymorphism, a genetic marker of physical performance and fitness, a risk factor for the colorectal cancer development in women?
Y1 - 2018
UR - http://hdl.handle.net/11268/9184
AB - INTRODUCTION: Exercise is one of the main mitochondrial regulation factors. The number of mitochondria can increase by 50-100%
depending on the training program, improving the energy production capacity of the organism, thus, improving global health. Besides,
several genetic polymorphisms in the nuclear genes related to the PPARGC1A-NRF-TFAM mitochondrial biogenesis pathway have been
found to correlate with the elite athlete status and with other markers of physical performance and fitness. In addition, several authors have shown that alterations in mitochondrial biogenesis of tumor cells could be risk factors for cancer progression. Thus, the aim of this study is to analyze the frequency of the main genetic polymorphisms involved in these mitochondrial biogenesis pathways in samples of healthy women and women with colorectal cancer.
METHODS: We analyzed 84 DNA samples from tumors of women with colorectal cancer (group 1) and 449 DNA samples from peripheral
blood of healthy women as control group (group 2) paired by age with group 1. All the samples were ceded by the Spanish National DNA
Bank Carlos III (BNADN) and donated voluntarily after informed consent signature. The genetic polymorphisms rs2267668, rs8192678,
rs6949152, rs12594956 and rs1937 of the genes PPARD, PPARGC1A, NRF1, NRF2 y TFAM, respectively, were analyzed by Q-PCR with a StepOne equipment (Life Technologies) with Taqman probes pre-designed for Life Technologies.
RESULTS: All the genetic polymorphisms (rs2267668, rs8192678, rs6949152, rs12594956 and rs1937) satisfied the Hardy-Weinberg equilibrium (p>0,05), except for the NRF-1 rs6949152 polymorphism in colorectal cancer (p=0.044). No significant differences were found between the genotypic frequencies of the control group and the colorectal cancer group, except for PPARGC1A and NRF-1 (p=0.035 and p=0.023, respectively). Furthermore, comparing the two groups for the TT genotype frequencies vs. CT and CC genotypes  requencies of the PPARGC1A rs8192678 polymorphism, we found that having the TT genotype increase 1.9 times the probability to develop colorectal cancer (OR 95% CI=1.905; 3.598-1.008).
CONCLUSION: The presence of the T allele in homozygosis of the PPARGC1A rs8192678 polymorphism may represent a risk factor for the
colorectal cancer development. Our results highlight the possible important role of the mitochondrial biogenesis in the development of
this kind of cancer. Taking into account that mitochondrial biogenesis is strongly increased by physical exercise, we suggest that it is necessary to further study: i) the role of mitochondrial biogenesis in cancer development and ii) the protective role that physical exercise may play against cancer through the stimulation of mitochondrial activity.
KW - Cáncer
KW - Mujeres
KW - Fisiología humana
KW - Cáncer
KW - Mujer
KW - Fisiología humana
LA - eng
PB - European College of Sport Science
ER -