Elucidating the role of 8q24 in colorectal cancer

All patients were newly diagnosed (within 1 year of diagnosis before enrollment in this study) and histologically confirmed colorectal adenocarcinoma patients who were recruited from the University of Texas MD Anderson Cancer Center between January 1990 and June 2008.

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Kaplan–Meier analysis showed that there was a significant trend for shorter median survival time with increasing number of risk alleles for the survival in patients with stage III CRC receiving 5-FU-based adjuvant chemotherapy (log-rank test In this study, we found that GWAS-identified CRC susceptibility SNPs may individually or jointly affect clinical outcomes for CRC patients.

To the best of our knowledge, this is the first study to report the association of CRC susceptibility loci with clinical outcomes.

However, 5-FU alone will only result in an absolute benefit in overall survival of are all components of transforming growth factor-β (TGF-β) pathway, suggesting that perturbation in TGF-β signaling pathway plays an important role in CRC susceptibility (7).

TGF-β pathway is also involved in the prognosis of the CRC (8), and overexpression of TGF-β signaling genes has been known to play a vital role in the progression of CRC (9).

There were no recruitment restrictions on age, gender, race, type of chemotherapy administered or cancer stage.

Demographic and epidemiologic data were collected using a structured self-administered questionnaire.Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of colorectal cancer (CRC).However, whether these loci affect clinical outcomes of CRC is not clear.The Cox proportional hazard model was used to assess the effect of individual SNPs on overall survival and recurrence-free survival, defined as the time from the date of surgical resection to the date of death/recurrence or last follow-up.Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting the Cox model while adjusting for age, gender, race, tumor location and histology grade.In this study, we genotyped 26 single nucleotide polymorphisms (SNPs) in 10 GWAS-identified CRC susceptibility regions and evaluated their associations with survival and recurrence in 285 stage II and III patients receiving fluorouracil-based adjuvant chemotherapy.

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