Lifestyle, Diet, and Colorectal Cancer Risk According to (Epi)genetic Instability: Current Evidence and Future Directions of Molecular Pathological Epidemiology.

Purpose Of Review: In this review, we describe molecular pathological epidemiology (MPE) studies from around the world that have studied diet and/or lifestyle factors in relation to molecular markers of (epi)genetic pathways in colorectal cancer (CRC), and explore future perspectives in this realm of research. The main focus of this review is diet and lifestyle factors for which there is evidence for an association with CRC as identified by the World Cancer Research Fund reports. In addition, we review promising hypotheses, that warrant consideration in future studies.

The CpG island methylator phenotype: what's in a name?

Although the CpG island methylator phenotype (CIMP) was first identified and has been most extensively studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to describe CpG island promoter methylation in other tumor types, including bladder, breast, endometrial, gastric, glioblastoma (gliomas), hepatocellular, lung, ovarian, pancreatic, renal cell, and prostate cancers, as well as for leukemia, melanoma, duodenal adenocarninomas, adrenocortical carcinomas, and neuroblastomas. CIMP has been reported to be useful for predicting prognosis and response to treatment in a variety of tumor types, but it remains unclear whether or not CIMP is a universal phenomenon across human neoplasia or if there should be cancer-specific definitions of the phenotype. Recently, it was shown that somatic isocitrate dehydrogenase-1 (IDH1) mutations, frequently observed in gliomas, establish CIMP in primary human astrocytes by remodeling the methylome.

Physical activity, occupational sitting time, and colorectal cancer risk in the Netherlands cohort study.

We investigated occupational energy expenditure and sitting time in the longest held job (in men only), nonoccupational physical activity, and former sports participation in relation to colorectal cancer endpoints. The Netherlands Cohort Study includes 120,852 participants who completed a self-administered questionnaire in 1986 when they were aged 55-69 years. By 2002, 1,819 male and 1,366 female colorectal cancer cases were available for case-cohort analyses.

The mTOR Pathway and the Role of Energy Balance Throughout Life in Colorectal Cancer Etiology and Prognosis: Unravelling Mechanisms Through a Multidimensional Molecular Epidemiologic Approach.

Timing of exposure to lifestyle factors that influence energy balance may differentially affect colorectal cancer (CRC) risk and prognosis. Caloric restriction in youth and short stature, as markers of early-life exposures, have shown to decrease CRC risk, whereas large body size and low physical activity levels in adulthood are established risk factors for CRC. Regarding prognosis, overweight, sarcopenia, and their co-occurrence (sarcopenic obesity) may negatively influence the health and quality of life of CRC survivors.

Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysis.

Background: How body size influences risk of molecular subtypes of colorectal cancer (CRC) is unclear. We investigated whether measures of anthropometry differentially influence risk of tumours according to BRAF c.1799T>A p.

Longitudinal changes in BMI in older adults are associated with meat consumption differentially, by type of meat consumed.

Hypotheses regarding the role of meat consumption in body weight modulation are contradictory. Prospective studies on an association between meat consumption and BMI change are limited. We assessed the association between meat consumption and change in BMI over time in 3902 men and women aged 55-69 y from the Netherlands Cohort Study.

The CpG island methylator phenotype in colorectal cancer: progress and problems.

In recent years, attention has focused on the biology and potential clinical importance of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). While it is generally well accepted that etiologically and clinically distinct subgroups exist in this disease, a precise definition of CIMP remains to be established. Here, we summarize existing literature that documents the prevalence of CIMP in CRC, with particular attention to the various methods and definitions used to classify a tumor as CIMP positive.

Body size and colorectal cancer risk after 16.3 years of follow-up: an analysis from the Netherlands Cohort Study.

A large body size may differentially influence risk of colorectal cancer (CRC) by anatomic location. The Netherlands Cohort Study includes 120,852 men and women aged 55-69 years who self-reported weight, height, and trouser/skirt size at baseline (1986), as well as weight at age 20 years. Derived variables included body mass index (BMI; weight (kg)/height (m)(2)), BMI at age 20 years, and BMI change.

Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP).

Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC).

Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.

Childhood and adolescent energy restriction and subsequent colorectal cancer risk: results from the Netherlands Cohort Study.

Background: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study.

Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n = 120 852).

Dietary flavonol, flavone and catechin intake and risk of colorectal cancer in the Netherlands Cohort Study.

Dietary flavonoids are hypothesized to be protective against colorectal cancer, yet findings have been inconsistent. We examined the association of dietary flavonol, flavone and catechin intake with colorectal cancer endpoints within the Netherlands Cohort Study (NLCS). In addition, we explored whether body mass index (BMI) may be an effect modifier of this association.

Self-reported clothing size as a proxy measure for body size.

Background: Few studies have considered the potential utility of clothing size as a predictor of diseases associated with body weight.

Methods: We used data on weight-stable men and women from a subcohort of the Netherlands Cohort Study to assess the correlation of clothing size with other anthropometric variables. Cox regression using the case-cohort approach was performed to establish whether clothing size can predict cancer risk after 13.

Pharmacoepigenomics in colorectal cancer: a step forward in predicting prognosis and treatment response.

Despite therapeutic innovations and increasing education on lifestyle to prevent colorectal cancer, it is still one of the most common cancer types, and for men the second cause of cancer-related death. Lately, much attention has been given to identify molecular markers involved in colorectal cancer prognosis and treatment with the aim to develop a more accurate classification system based on (epi)genetic alterations and, in addition, find markers that could potentially enhance management of colorectal cancer by predicting treatment response in advance. Although many genetic markers have been claimed to have prognostic or predictive influence, results are often inconclusive and, with some exception, they are not used in standard practice.

Higher dietary flavone, flavonol, and catechin intakes are associated with less of an increase in BMI over time in women: a longitudinal analysis from the Netherlands Cohort Study.

Background: Dietary flavonoids are suggested to have antiobesity effects. Prospective evidence of an association between flavonoids and body mass index (BMI) is lacking in general populations.

Objective: We assessed this association between 3 flavonoid subgroups and BMI over a 14-y period in 4280 men and women aged 55-69 y at baseline from the Netherlands Cohort Study.