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Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Multivariable hazard ratios and 95% confidence intervals (CIs) were calculated for the association between MO3PUFA and disease-free survival (DFS) and overall survival according to KRAS and BRAFV600E mutations and DNA mismatch repair (MMR) status. Higher MO3PUFA intake was associated with improved 3-year DFS for KRAS wild-type tumors (77% vs. 73%; HR: 0.84; 95% CI: 0.67-1.05) but not KRAS-mutant tumors (64% vs. 70%; HR: 1.30; 95% CI: 0.97-1.73; Pinteraction = 0.02). Similar heterogeneity was found by MMR (Pinteraction = 0.14): higher MO3PUFA was associated with better 3-year DFS for tumors with deficient MMR (72% vs. 67%) but not proficient MMR (72% vs. 72%). No heterogeneity was found by BRAFV600E mutation. Similar findings were obtained for overall survival. In conclusion, we found a suggestive beneficial association between higher MO3PUFA intake and improved survival among stage III colon cancer patients with wild-type KRAS and deficient MMR. Given the relatively small number of cases with tumor molecular assessments, further studies, preferably through pooled analyses of multiples cohorts, are needed to validate our findings.

Prostate cancer has high heritability. Healthy lifestyle has been associated with lower lethal prostate cancer risk among men at increased genetic susceptibility, but the role of healthy dietary patterns remains unknown. We prospectively followed 10,269 genotyped men in the Health Professionals Follow‐up Study (1993–2019). Genetic risk was quantified using an established polygenic risk score (PRS). Five dietary patterns were investigated: healthy eating index, Mediterranean, diabetes risk‐reducing, hyperinsulinemic and inflammatory diet. Overall and lethal prostate cancer rates (metastatic disease/prostate cancer‐specific death) were analyzed using multivariable Cox proportional hazards models. During 26 years of follow‐up, 2133 overall and 253 lethal prostate cancer events were documented. In the highest PRS quartile, higher adherence to a diabetes risk‐reducing diet was associated with lower rates of overall (top vs. bottom quintile HR [95% CI], 0.74 [0.58–0.94]) and lethal prostate cancer (0.43 [0.21–0.88]). A low insulinemic diet was associated with similar lower rates (overall, 0.76 [0.60–0.95]; lethal, 0.46 [0.23–0.94]). Other dietary patterns showed weaker, but similar associations. In the highest PRS quartile, men with healthy lifestyles based on body weight, physical activity, and low insulinemic diet had a substantially lower rate (0.26 [0.13–0.49]) of lethal prostate cancer compared with men with unhealthy lifestyles, translating to a lifetime risk of 3.4% (95% CI, 2.3%–5.0%) among those with healthy lifestyles and 9.5% (5.3%–16.7%) among those with unhealthy lifestyles. Our findings indicate that lifestyle modifications lowering insulin resistance and chronic hyperinsulinemia could be relevant in preventing aggressive prostate cancer among men genetically predisposed to prostate cancer. [ABSTRACT FROM AUTHOR]

Serrated polyps (SPs) are precursors to one‐third of colorectal cancers (CRCs), with histological subtypes: hyperplastic polyps (HPs), sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). The incidence of early‐onset CRC before the age of 50 is increasing, with limited understanding of SPs in younger cohorts. Using a large colonoscopy‐based cohort, we characterized epidemiologic profiles of SP subtypes, compared to conventional adenomas, with secondary analysis on early‐onset polyps. Ninety‐four thousand four hundred and twenty‐seven patients underwent screening colonoscopies between 2010 and 2018. Demographic, endoscopic and histopathologic characteristics of each polyp subtype were described. High‐risk polyps included SSLs ≥10 mm/with dysplasia and conventional adenomas ≥10 mm/with tubulovillous/villous histology/high‐grade dysplasia. We examined polyp prevalence with age and compared early‐ (age < 50) and late‐onset polyps (age ≥ 50). Eighteen thousand one hundred and twenty‐five patients had SPs (4357 SSLs, 15 415 HPs, 120 TSAs) and 26 699 had conventional adenomas. High‐risk SSLs were enriched in the ascending colon (44.1% vs 2.6‐35.8% for other locations; P <.003). Early‐ and late‐onset SPs had similar subsite distribution. Early‐onset conventional adenomas were more enriched in the distal colon/rectum (51.8% vs 43.4%, P <.001). Multiple conventional adenomas were more represented in late‐onset groups (40.8% vs 33.8%, P <.001), with no difference in SSLs. The prevalence of conventional adenomas/high‐risk conventional adenomas increased continuously with age, whereas the prevalence of SSLs/high‐risk SSLs was stable from age 40 years onwards. A higher proportion of women were diagnosed with early‐onset than late‐onset SSLs (62.9% vs 57.6%, P =.03). Conventional adenomas, SSLs, early‐ and late‐onset polyps have distinct epidemiology. The findings have implications for improved colonoscopy screening and surveillance and understanding the etiologic heterogeneity of CRC. [ABSTRACT FROM AUTHOR]

Evidence links the liver to development of colorectal cancer (CRC). However, it remains unknown how liver function may influence CRC risk in the general population. We conducted a prospective cohort study in the UK Biobank of 375 693 participants who provided blood samples in 2006 to 2010. Circulating levels of liver function markers (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TBIL], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], total protein [TP] and albumin [ALB]) were measured. Incident cancer cases were identified through linkage to the national cancer registry up to 2019. Repeated biomarker measurements were available from a subset of 11 320 participants who were re‐assessed in 2012 to 2013. After a median follow‐up of 10.0 years, we documented 2662 cases of CRC. Circulating levels of ALT, AST, TBIL, GGT, TP and ALB at baseline were inversely associated with CRC risk (P <.01), with multivariable hazard ratio (95% confidence interval) comparing decile 10 vs 1 of 0.62 (0.51‐0.75), 0.63 (0.53‐0.75), 0.85 (0.72‐1.02), 0.74 (0.61‐0.89), 0.70 (0.59‐0.84) and 0.66 (0.55‐0.79), respectively. Strengthened associations were found after recalibration for repeated measurements. The associations appeared stronger for proximal colon cancer than distal colon cancer and rectal cancer, but consistent for early‐, mid‐ and late‐onset CRC. In a large cohort of general population, the UK Biobank, higher circulating levels of ALT, AST, TBIL, GGT, TP and ALB, largely within the normal range, were associated with a lower risk of CRC. The findings support a link between liver function and CRC, and may spur future research on the gut‐microbiota‐liver axis. What's new? Recent studies have reported a possible relationship between circulating liver metabolites and colorectal cancer (CRC) risk, but nothing has been proven conclusively. Here, the authors examined the relationship between various circulating liver function markers and CRC risk, using data from the UK Biobank. Over 10 years of follow up, they documented 2,662 cases of CRC. They tested levels of 7 different circulating liver function markers. For 6 of the markers, higher circulating levels corresponded to a lower risk of CRC. The work may prompt future investigations into the gut‐microbiota‐liver axis. [ABSTRACT FROM AUTHOR]

The influence of polyunsaturated fatty acids (PUFAs) on risk of colorectal cancer precursors remains largely unknown. We examined the associations of erythrocyte PUFAs, including n−3 and n−6 PUFAs, with risk of colorectal conventional adenomas and serrated polyps in 4517 participants from three US prospective cohorts who had provided a blood sample and undergone at least one endoscopic examination. We calculated the multivariable odds ratios (ORs) per 1 SD increment in individual PUFAs and the ratio of n−6/n−3 PUFAs. We considered P <.005 statistically significant to account for multiple testing. During a median of 20 years of follow‐up, we documented 493 conventional adenomas and 316 serrated polyps. After adjusting for various CRC risk factors, no associations for PUFAs achieved the stringent statistical significance for either conventional adenomas or serrated polyps (ORs per 1 SD ranged from 0.90 to 1.14). Some associations achieved nominal significance (P <.05), including the association of dihomogammalinolenic acid (DGLA) (20:3, n−6) with lower risk of conventional adenomas (OR = 0.91; 95% confidence interval [CI] = 0.83‐1.00), total n−6 PUFAs with higher risk of proximal serrated polyps (OR = 1.32; 95% CI = 1.01‐1.74) and eicosadienoic acid (20:2, n−6) and DGLA with lower risk of advanced adenomas (OR = 0.83; 95% CI = 0.71‐0.97 and OR = 0.84; 95% CI = 0.72‐0.98, respectively). Our findings indicate that erythrocyte PUFAs in a typical American diet are unlikely to have a substantial influence on risk of colorectal cancer precursors. The subgroup associations require further confirmation. What's new? The influence of polyunsaturated fatty acids on risk of colorectal cancer precursors remains largely unknown. Over a median follow‐up duration of 20 years, this prospective study examined the associations of erythrocyte n‐3 and n‐6 polyunsaturated fatty acids with risk of colorectal cancer precursors in three large prospective cohorts in the United States. No statistically significant association was found at α=0.005 level for any of the fatty acids with either conventional adenomas or serrated polyps. The findings indicate that n‐3 and n‐6 polyunsaturated fatty acids in a typical American diet are unlikely to have a substantial impact on colorectal cancer precursors. [ABSTRACT FROM AUTHOR]