Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.

PURPOSES: Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants. METHODS: Genomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing. RESULTS: The T allele is more frequent in controls than in patients (P < 0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P = 0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P = 0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P = 0.001). CONCLUSIONS: The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.

Predictive factors of years of potential life lost by colorectal cancer.

OBJECTIVE: To evaluate the impact of colorectal cancer (CRC) by estimating the years of potential life lost (YPLL) by this neoplasm in a cohort of patients, as well as to define the predictive factors of YPLL. METHODS: A descriptive cross-sectional study of 980 consecutive patients diagnosed and treated because of CRC in our institution between 1985 and 2002 was carried out. Demographic, clinical, pathological, surgical, hospital stay, complications, and mortality variables were recorded. The primary endpoint of this study was to calculate individual YPLL. Univariate analysis was performed to compare each independent variable with the variable YPLL. All clinically relevant variables significantly associated with YPLL were included in an ordinal regression model to identify independent factors prognostic of YPLL. RESULTS: The final study sample was 794 patients, 413 (52%) men and 381 (48%) women, mean age 65.3 years [confidence interval (CI) 95%: 64.4-66.2 years; SD: 12.8]. The mean global YPLL for the 351 patients who died of CRC was 15.2 years (SD: 10.7; CI 95%: 14.1-16.3). Lower age [odds ratio (OR)=0.98; CI 95%: 0.97-0.98], male sex (OR=1.19; CI 95%: 1.00-1.43), lower tumor, nodes, metastasis (TNM) stage (OR=0.29; CI 95%: 0.24-0.35), and rectum localization of the tumor (OR=1.37; CI 95%: 1.14-1.64) were independent prognostic factors for YPLL. CONCLUSION: In our community, the mean number of YPLL by CRC exceeds 15 years. Lower age, male sex, higher TNM stage, and rectum localization are negative predictors of YPLL.

Can early diagnosis of symptomatic colorectal cancer improve the prognosis?

Patients with colorectal cancer continue to present with relatively advanced tumors. Delay in diagnosis is often believed to have been a contributing factor, and the validity of this hypothesis has seldom been questioned. The aim of this study was to establish whether a delay in diagnosis is related to long-term survival and if the most frequent symptoms were related to the stage or time at which the carcinoma was diagnosed. Data from 660 patients surgically treated for uncomplicated colorectal carcinoma in our institution between 1985 and 2000 were analyzed retrospectively. Age, sex, initial symptoms, duration of symptoms, neoplasm location, curative surgery, TNM stage, and survival time were the variables recorded. Patients were classified into two groups according to symptom duration: < 3 months versus >/= 3 months. Comparative statistical analysis was performed for the two groups as well as the initial symptom, TNM stage, and survival time. Also, the initial symptoms most frequently reported were compared with the TNM stage. The two groups were found to be equal with regard to distribution of age, gender, location of the neoplasm, type of surgery performed, and TNM stage. We found that symptom duration was shortened in the presence of abdominal pain ( p = 0.002) [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.35-0.80] and was delayed in the presence of an anemic syndrome ( p = 0.006) (OR 2.4; 95% CI 1.27-4.56). Also, the stage of the neoplasm was related to rectal bleeding ( p < 0.001) and abdominal pain ( p = 0.008). The log-rank test indicated that duration of symptoms was not related to long-term survival ( p = 0.90). We concluded that the duration of colorectal cancer symptoms is not related to the stage or prognosis of tumors.