Dataset Information

Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer.

ABSTRACT:

Purpose

We hypothesized that adverse prognostic associations of specific tumor molecular factors vary by patient age at colorectal cancer diagnosis.

Experimental design

We examined the prognostic associations and interactions by age at colorectal cancer diagnosis (<60 vs. 60-74 vs. ≥75 years old) of key molecular factors-CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and PIK3CA mutations, and nuclear CTNNB1 expression status-on colorectal cancer-specific survival (CSS) and overall survival (OS), using 1,280 incident colorectal cancer cases (median age, 69 years; range, 38-91 years) within the Nurses' Health Study and Health Professionals Follow-up Study cohorts.

Results

MSI-high was associated with better survival, whereas BRAF mutation was associated with worse survival, but these associations did not appreciably differ by age group. Status of CIMP, KRAS mutation, or PIK3CA mutation was not associated with prognosis regardless of age. Nuclear CTNNB1 expression was associated with a trend toward worse prognosis among older adults [age ≥ 75 years; multivariate HR, 1.67; 95% confidence interval (CI), 0.89-3.13 (for CSS); multivariate HR, 1.44; 95% CI, 0.93-2.24 (for OS)] but not among younger patients, and there was a statistically significant interaction by age (Pinteraction = 0.03 for CSS; Pinteraction = 0.007 for OS).

Conclusions

Tumor nuclear CTNNB1 expression may be associated with higher mortality among older patients with colorectal cancer but not among younger patients. Our findings need to be confirmed in independent datasets. Detailed exploration of tumor molecular signatures in older patients with colorectal cancer in large populations is warranted.

SUBMITTER: McCleary NJ

PROVIDER: S-EPMC4888056 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Publications

Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer.

McCleary Nadine J NJ Sato Kaori K Nishihara Reiko R Inamura Kentaro K Morikawa Teppei T Zhang Xuehong X Wu Kana K Yamauchi Mai M Kim Sun A SA Sukawa Yasutaka Y Mima Kosuke K Qian Zhi Rong ZR Fuchs Charles S CS Ogino Shuji S Meyerhardt Jeffrey A JA

Clinical cancer research : an official journal of the American Association for Cancer Research 20151021 6

<h4>Purpose</h4>We hypothesized that adverse prognostic associations of specific tumor molecular factors vary by patient age at colorectal cancer diagnosis.<h4>Experimental design</h4>We examined the prognostic associations and interactions by age at colorectal cancer diagnosis (<60 vs. 60-74 vs. ≥75 years old) of key molecular factors-CpG island methylator phenotype (CIMP), microsatellite instability (MSI), KRAS, BRAF, and PIK3CA mutations, and nuclear CTNNB1 expression status-on colorectal can ...[more]

PMID: 26490308

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Project description:BackgroundColorectal cancer (CRC) is one of the most common cancers in the world. The number of elderly patients with CRC increases due to aging of the population. There are few studies that examined chemotherapy and prognostic factors in metastatic colorectal cancer (mCRC) patients aged ≥ 80 years. We assessed the efficacy of chemotherapy and prognostic factors among patients with mCRC aged ≥ 80 years.MethodsWe retrospectively analyzed clinical and laboratory findings of 987 patients newly diagnosed with CRC at Asahi General Hospital (Chiba, Japan) between January 2012 and December 2016. The Kaplan-Meier method was used for the overall survival (OS) and the log-rank test was used to identify difference between patients. A multivariate Cox proportional hazard regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs) of prognostic factors among super-elderly patients.ResultsIn total, 260 patients were diagnosed with mCRC (super-elderly group: n = 43, aged ≥ 80 years and younger group, n = 217, aged < 80 years). The performance status and nutritional status were worse in the super-elderly group than in the younger group. The OS of super-elderly patients who received chemotherapy was worse than that of younger patients (18.5 vs. 28.8 months; P = 0.052), although the difference was not significant. The OS of patients who received chemotherapy tended to be longer than that of those who did not; however, there were no significant differences in OS in the super-elderly group (18.5 vs. 8.4 months P = 0.33). Multivariate analysis revealed that carcinoembryonic antigen levels ≥ 5 ng/mL (hazard ratio: 2.27; 95% CI 1.09-4.74; P = 0.03) and prognostic nutritional index ≤ 35 (hazard ratio: 8.57; 95% CI 2.63-27.9; P = 0.0003) were independently associated with poor OS in the super-elderly group.ConclusionsPatients with mCRC aged ≥ 80 years had lower OS than younger patients even though they received chemotherapy. Carcinoembryonic antigen and prognostic nutritional index were independent prognostic factors in super-elderly patients with mCRC, but chemotherapy was not.Trial registrationretrospectively registered.

Project description:BackgroundColorectal cancer defined as cancer of the colon or rectum, is the third most frequently diagnosed cancer in men and the second in women, and, according to the World Health Organization database GLOBOCAN, it accounts for nearly 1.4 million new cases annually worldwide. The occurrence of colorectal cancer is associated with nonmodifiable risk factors, including age and hereditary factors, as well as with modifiable environmental and lifestyle factors.MethodsThe study included 800 patients, 400 diagnosed with colorectal cancer and 400 within the control group, who gave their written informed consent to participate in the study. Patients with cancer other than colorectal cancer were randomly selected for control group I, and patients with no cancer diagnosis were selected for control group II. The method used was a case-control study - an observational and analytical study with a control group, conducted among patients of the Clinical Oncology Centre and the Provincial Hospital in the years 2019-2020. The study comparing the exposure was carried out in a group of people who developed the endpoint, that is colorectal cancer, with the exposure in a well-matched group of controls who did not reach the endpoint. Assessment of activity and BMI was used according to WHO recommendations, as well as the expert system. The data were tested for the distribution and the homogeneity of variance was validated before applying the parameter tests. Comparison of quantitative variables between groups was performed using ANOVA.ResultsThe mean age of the patients was 64.53 ± 8.86 years, of the control group I - 59.64 ± 9.33 and the control group II - 57.5 (7.83). There was a strong positive association between the incidence of ulcerative colitis and the risk of colorectal cancer (P < .01). Among obese subjects, the risk of developing colorectal cancer was 1.27 (95% CI, 1.06-1.53) compared with nonobese subjects. A strong positive relationship was found between low physical activity converted to metabolic equivalent of MET effort per week and the risk of colorectal cancer (P < .001). The relative risk for current smokers was 2.17 (95% CI 1.79-2.66). There was an association between higher fat consumption and higher red meat consumption and the risk of developing colorectal cancer (P < .01).ConclusionsObesity, low physical activity, active and passive smoking and high salt and red meat consumption have been associated with an increased risk of colorectal cancer. These findings provide further evidence of the importance of maintaining a healthy lifestyle.

Dataset Information

Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer.

Purpose

Experimental design

Results

Conclusions

Publications

Prognostic Utility of Molecular Factors by Age at Diagnosis of Colorectal Cancer.

Similar Datasets

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