External validation of the colorectal cancer risk score LiFeCRC using food frequency questions in the HUNT study.

PURPOSE: To mitigate the increasing colorectal cancer (CRC) incidence globally and prevent CRC at the individual level, individual lifestyle information needs to be easily translated into CRC risk assessment. Several CRC risk prediction models exist and their clinical usefulness depends on their ease of use. Our objectives were to assess and externally validate the LiFeCRC score in our independent, unselected population and to investigate the use of simpler food frequency measurements in the score. METHODS: Incidental colon and rectal cancer cases were compared to the general population among 78,580 individuals participating in a longitudinal health study in Norway (HUNT). Vegetable, dairy product, processed meat and sugar/confectionary consumption was scored based on food frequency. The LiFeCRC risk score was calculated for each individual. RESULTS: Over a median of 10 years following participation in HUNT, colon cancer was diagnosed in 1355 patients and rectal cancer was diagnosed in 473 patients. The LiFeCRC score using food frequencies demonstrated good discrimination in CRC overall (AUC 0.77) and in sex-specific models (AUC men 0.76 and women 0.77) in this population also including individuals ≥ 70 years and patients with diabetes. It performed somewhat better in colon (AUC 0.80) than in rectal cancer (AUC 0.72) and worked best for female colon cancer (AUC 0.81). CONCLUSION: Readily available clinical variables and food frequency questions in a modified LiFeCRC score can identify patients at risk of CRC and may improve primary prevention by motivating to lifestyle change or participation in the CRC screening programme.

Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study.

BACKGROUND: Colorectal cancer (CRC) is often diagnosed in advanced stages. Circulating tumour DNA (ctDNA) has been proposed as an early diagnostic biomarker. However, as a screening tool, ctDNA has mainly been studied in selected populations at the time of clinical diagnosis. The aim of this study was to detect CRC by known ctDNA markers up to 2 years prior to clinical diagnosis. METHODS: In this case-control study, methylated ctDNA markers were detected in plasma samples from 106 healthy controls and 106 individuals diagnosed with CRC within 24 months following participation in The Trøndelag Health Study. RESULTS: The most specific single markers were BMP3, FLI1, IKZF1, SFRP1, SFRP2, NPTX2, SLC8A1 and VIM (specificity >70%). When combining these into a panel, the CRC sensitivity was 43% (95% CI 42.7-43.4) and the CRC specificity was 86% (95% CI 85.7-86.2). The findings were reproduced in an independent validation set of samples. CONCLUSIONS: Detection of known methylated ctDNA markers of CRC is possible up to 2 years prior to the clinical diagnosis in an unselected population resembling the screening setting. This study supports the hypothesis that some patients could be diagnosed earlier, if ctDNA detection was part of the CRC screening programme.

Risk factors for right colon, left colon and rectal cancers differ between men and women: the population-based HUNT study in Norway.

AIM: The aim of this study was to assess established risk factors for colorectal cancer (CRC) separately for right colon, left colon and rectal cancer in men and women. METHOD: This was a prospective cohort study comparing incidental CRC cases and the general population participating in a longitudinal health study in Norway (the HUNT study). RESULTS: Among 78 580 participants (36 825 men and 41 754 women), 1827 incidental CRCs were registered (931 men and 896 women). Among men, the risk of cancer at all locations increased with age [HR 1.46 (1.40-1.51), HR 1.32 (1.27-1.36), HR 1.30 (1.25-1.34) per 5 years for right colon, left colon and rectal cancer, respectively] and the risk of left colon cancer increased with higher body mass index [HR 1.28 (1.12-1.46) per 5 kg/m2 ]. The risk of right colon cancer (RCC) increased with smoking [HR 1.07 (1.04-1.10) per 5 pack years]. Among women, the risk of cancer at all locations increased with age [HR 1.38 (1.34-1.43), HR 1.23 (1.19-1.27), HR 1.20 (1.16-1.24) per 5 years] and smoking [HR 1.07 (1.02-1.12), HR 1.07 (1.02-1.12), HR 1.10 (1.05-1.17) per 5 pack years] for right colon, left colon and rectal cancer, respectively. The risk of RCC increased with night shift work [HR 1.93 (1.22-3.05)]. CONCLUSION: The risk factors for developing CRC differ by anatomical location and sex. The relationship between risk factors and CRC may be more nuanced than previously known.