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Systemic inflammation markers and cancer incidence in the UK Biobank.

ABSTRACT: Systemic inflammation markers have been linked to increased cancer risk and mortality in a number of studies. However, few studies have estimated pre-diagnostic associations of systemic inflammation markers and cancer risk. Such markers could serve as biomarkers of cancer risk and aid in earlier identification of the disease. This study estimated associations between pre-diagnostic systemic inflammation markers and cancer risk in the prospective UK Biobank cohort of approximately 440,000 participants recruited between 2006 and 2010. We assessed associations between four immune-related markers based on blood cell counts: systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and risk for 17 cancer sites by estimating hazard ratios (HR) using flexible parametric survival models. We observed positive associations with risk for seven out of 17 cancers with SII, NLR, PLR, and negative associations with LMR. The strongest associations were observed for SII for colorectal and lung cancer risk, with associations increasing in magnitude for cases diagnosed within one year of recruitment. For instance, the HR for colorectal cancer per standard deviation increment in SII was estimated at 1.09 (95% CI 1.02-1.16) in blood drawn five years prior to diagnosis and 1.50 (95% CI 1.24-1.80) in blood drawn one month prior to diagnosis. We observed associations between systemic inflammation markers and risk for several cancers. The increase in risk the last year prior to diagnosis may reflect a systemic immune response to an already present, yet clinically undetected cancer. Blood cell ratios could serve as biomarkers of cancer incidence risk with potential for early identification of disease in the last year prior to clinical diagnosis.

SUBMITTER: Nost TH

PROVIDER: S-EPMC8416852 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceVigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity (PA) for cancer prevention, although structured longer bouts of VPA (via traditional exercise) are unappealing or inaccessible to many individuals.ObjectivesTo evaluate the dose-response association of device-measured daily vigorous intermittent lifestyle physical activity (VILPA) with incident cancer, and to estimate the minimal dose required for a risk reduction of 50% of the maximum reduction.Design, setting, and participantsThis was a prospective cohort analysis of 22 398 self-reported nonexercising adults from the UK Biobank accelerometry subsample. Participants were followed up through October 30, 2021 (mortality and hospitalizations), or June 30, 2021 (cancer registrations).ExposuresDaily VILPA of up to 1 and up to 2 minutes, assessed by accelerometers worn on participants' dominant wrist.Main outcomes and measuresIncidence of total cancer and PA-related cancer (a composite outcome of 13 cancer sites associated with low PA levels). Hazard ratios and 95% CIs were estimated using cubic splines adjusted for age, sex, education level, smoking status, alcohol consumption, sleep duration, fruit and vegetable consumption, parental cancer history, light- and moderate-intensity PA, and VPA from bouts of more than 1 or 2 minute(s), as appropriate.ResultsThe study sample comprised 22 398 participants (mean [SD] age, 62.0 [7.6] years; 10 122 [45.2%] men and 12 276 [54.8%] women; 21 509 [96.0%] White individuals). During a mean (SD) follow-up of 6.7 (1.2) years (149 650 person-years), 2356 total incident cancer events occurred, 1084 owing to PA-related cancer. Almost all (92.3%) of VILPA was accrued in bouts of up to 1 minute. Daily VILPA duration was associated with outcomes in a near-linear manner, with steeper dose-response curves for PA-related cancer than total cancer incidence. Compared with no VILPA, the median daily VILPA duration of bouts up to 1 minute (4.5 minutes per day) was associated with an HR of 0.80 (95% CI, 0.69-0.92) for total cancer and 0.69 (95% CI, 0.55-0.86) for PA-related cancer. The minimal dose was 3.4 minutes per day for total (HR, 0.83; 95% CI, 0.73-0.93) and 3.7 minutes for PA-related (HR, 0.72; 95% CI, 0.59-0.88) cancer incidence. Findings were similar for VILPA bout of up to 2 minutes.Conclusions and relevanceThe findings of this prospective cohort study indicate that small amounts of VILPA were associated with lower incident cancer risk. Daily VILPA may be a promising intervention for cancer prevention in populations not able or motivated to exercise in leisure time.

Project description:BackgroundAdiposity is a strong risk factor for cancer incidence and mortality. However, most of the evidence available has focused on body mass index (BMI) as a marker of adiposity. There is limited evidence on relationships of cancer with other adiposity markers, and if these associations are linear or not. The aim of this study was to investigate the associations of six adiposity markers with incidence and mortality from 24 cancers by accounting for potential non-linear associations.MethodsA total of 437,393 participants (53.8% women; mean age 56.3 years) from the UK Biobank prospective cohort study were included in this study. The median follow-up was 8.8 years (interquartile range 7.9 to 9.6) for mortality and 9.3 years (IQR 8.6 to 9.9) for cancer incidence. Adiposity-related exposures were BMI, body fat percentage, waist-hip ratio, waist-height ratio, and waist and hip circumference. Incidence and mortality of 24 cancers sites were the outcomes. Cox proportional hazard models were used with each of the exposure variables fitted separately on penalised cubic splines.ResultsDuring follow-up, 47,882 individuals developed cancer and 11,265 died due to cancer during the follow-up period. All adiposity markers had similar associations with overall cancer incidence. BMI was associated with a higher incidence of 10 cancers (stomach cardia (hazard ratio per 1 SD increment 1.35, (95% CI 1.23; 1.47)), gallbladder (1.33 (1.12; 1.58)), liver (1.27 (1.19; 1.36)), kidney (1.26 (1.20; 1.33)), pancreas (1.12 (1.06; 1.19)), bladder (1.09 (1.04; 1.14)), colorectal (1.10 (1.06; 1.13)), endometrial (1.73 (1.65; 1.82)), uterine (1.68 (1.60; 1.75)), and breast cancer (1.08 (1.05; 1.11))) and overall cancer (1.03 (1.02; 1.04)). All these associations were linear except for breast cancer in postmenopausal women. Similar results were observed when other markers of central and overall adiposity were used. For mortality, nine cancer sites were linearly associated with BMI and eight with waist circumference and body fat percentage.ConclusionAdiposity, regardless of the marker used, was associated with an increased risk in 10 cancer sites.

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Systemic inflammation markers and cancer incidence in the UK Biobank.

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