FoR at modest intensity is experienced by most long-term cancer survivors. Future studies should address determinants and consequences of FoR in more detail. Validated instruments providing cut-offs for severity/clinical significance of FoR should be developed and utilized. Efficient interventions should be implemented to reduce detrimental effects of FoR.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1 . In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P <5×10 −8 , bringing the number of known independent signals for CRC to approximately 100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs, somatic drivers, and support a role of immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of underlying biology, and impact personalized screening strategies and drug development.

Deficits in emotional and social functioning and specific limitations like fatigue, dyspnea, insomnia, constipation, diarrhea, and financial difficulties are main factors hampering the QOL among colorectal cancer patients and seem to affect predominantly younger patients.

Opinion statementCancer-related fatigue (CRF) is a problem for a significant proportion of cancer survivors during and after active cancer treatment. However, CRF is underdiagnosed and undertreated. Interventions are available for CRF although there is no gold standard. Based on current level of evidence, exercise seems to be most effective in preventing or ameliorating CRF during the active- and posttreatment phases.

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

There is some variation regarding age at initiation of screening for colorectal cancer (CRC) between countries, but the same age of initiation is generally recommended for women and men within countries, despite important gender differences in the epidemiology of CRC. We have explored whether, and to what extent, these differences would be relevant regarding age at initiation of CRC screening. Using population-based cancer registry data from the US and national mortality statistics from different countries, we looked at cumulative 10-year incidence and mortality of CRC reached among men at ages 50, 55, and 60, and found that women mainly reached equivalent levels when 4 to 8 years older. The gender differences were remarkably constant across populations and over time. These patterns suggest that gender differentiation of age at initiation may be worthwhile to utilise CRC-screening resources more efficiently. With more than one million new cases and more than 500 000 deaths per year, colorectal cancer (CRC) is the third commonest cancer and the fourth commonest cancer cause of death worldwide (Parkin et al, 2005). Owing to its typically slow development, there is a large potential for reducing the burden of the disease by early detection and removal of precancerous lesions or early cancer stages. Various screening examinations, including faecal occult blood testing (FOBT), sigmoidoscopy, and colonoscopy have meanwhile been recommended by expert committees and implemented in screening offers in a number of countries (e.g. Winawer et al, 2003;Schmiegel et al, 2004;Malila et al, 2005;Smith et al, 2006). Regarding the age at initiation of screening, which is a crucial parameter for the effectiveness and cost-effectiveness of screening programmes (Vijan et al, 2001), there is some variation between countries (typically ranging from 50 to 60 years for the population at average risk). However, within countries, the same age of initiation is generally recommended for women and men, despite important gender differences in the epidemiology of CRC. In particular, age-specific CRC incidence and mortality are lower in women than in men, which implies that women reach comparable levels of CRC incidence and mortality at higher ages than men. This paper aims to address the question whether and to what extent these epidemiological differences might be relevant for defining age at initiation of CRC screening among women and men. METHODS Outcome measureWhen attempting to translate the gender differences in the epidemiology of CRC into gender-specific ages at initiation of screening, it is first necessary to define an appropriate outcome measure. In a screening programme that primarily aims at the early detection of CRC, as applies to FOBT-based screening, (cumulative) age-and sex-specific CRC incidence appears to be a natural choice. In a screening programme that aims to detect both CRC and its precursors (adenomas), as applies to endoscopy-based screening, the epidemiology of adenomas might also be considered. However, if the time...

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