Interactions of platelets with obesity in relation to lung cancer risk in the UK Biobank cohort

Abstract

Background Platelet count (PLT) is associated positively with lung cancer risk but has a more complex association with body mass index (BMI), positive only in women (mainly never smokers) and inverse in men (mainly ever smokers), raising the question whether platelets interact with obesity in relation to lung cancer risk. Prospective associations of platelet size (an index of platelet maturity and activity) with lung cancer risk are unclear. Methods We examined the associations of PLT, mean platelet volume (MPV), and platelet distribution width (PDW) (each individually, per one standard deviation increase) with lung cancer risk in UK Biobank men and women using multivariable Cox proportional hazards models adjusted for BMI and covariates. We calculated Relative Excess Risk from Interaction (RERI) with obese (BMI ≥ 30 kg/m2), dichotomising platelet parameters at ≥ median (sex-specific), and multiplicative interactions with BMI (continuous scale). We examined heterogeneity according to smoking status (never, former, current smoker) and antiaggregant/anticoagulant use (no/yes). Results During a mean follow-up of 10.4 years, 1620 lung cancers were ascertained in 192,355 men and 1495 lung cancers in 218,761 women. PLT was associated positively with lung cancer risk in men (hazard ratio HR = 1.14; 95% confidence interval (CI): 1.09–1.20) and women (HR = 1.09; 95%CI: 1.03–1.15) but interacted inversely with BMI only in men (RERI = − 0.53; 95%CI: − 0.80 to − 0.26 for high-PLT-obese; HR = 0.92; 95%CI = 0.88–0.96 for PLT*BMI). Only in men, MPV was associated inversely with lung cancer risk (HR = 0.95; 95%CI: 0.90–0.99) and interacted positively with BMI (RERI = 0.27; 95%CI = 0.09–0.45 for high-MPV-obese; HR = 1.08; 95%CI = 1.04–1.13 for MPV*BMI), while PDW was associated positively (HR = 1.05; 95%CI: 1.00–1.10), with no evidence for interactions. The associations with PLT were consistent by smoking status, but MPV was associated inversely only in current smokers and PDW positively only in never/former smokers. The interactions with BMI were retained for at least eight years of follow-up and were consistent by smoking status but were attenuated in antiaggregant/anticoagulant users. Conclusions In men, PLT was associated positively and MPV inversely with lung cancer risk and these associations appeared hindered by obesity. In women, only PLT was associated positively, with little evidence for interaction with obesity.

Prospective associations of leucocyte subtypes and obesity with the risk of developing cutaneous malignant melanoma in the UK Biobank cohort

“…Menopausal status (pre-menopausal, post-menopausal, unknown) and hormone replacement therapy (HRT) use (never, past, current) were defined similarly to [ 12 ]. Detailed categories for smoking status and intensity were defined according to [ 13 ]: never smoked; just tried; former occasional smoker; former regular quit ≥ 20 years; former regular quit ≥ 10 years; former regular quit < 10 years; current occasional smoker; current regular ≤ 10 cigarettes/day; current regular > 10 cigarettes/day. The following covariates were defined as previously described in [ 8 ]: time of blood collection (< 12:00; 12:00 to < 16:00; ≥16:00), fasting time (0–2 h; 3–4 h; ≥5 h), self-reported diabetes (no/yes, including all participants reporting use of anti-diabetic drugs and assuming that all participants with self-reported diabetes were treated), use of lipid lowering drugs (additionally including cholestyramine products), and antihypertensive drugs.…”

“…The following covariates were defined as previously described in [ 8 ]: time of blood collection (< 12:00; 12:00 to < 16:00; ≥16:00), fasting time (0–2 h; 3–4 h; ≥5 h), self-reported diabetes (no/yes, including all participants reporting use of anti-diabetic drugs and assuming that all participants with self-reported diabetes were treated), use of lipid lowering drugs (additionally including cholestyramine products), and antihypertensive drugs. Use of non-steroidal anti-inflammatory drugs (NSAID) and antiaggregant/anticoagulants was defined according to [ 13 ]. Use of any medication within the corresponding category was coded as yes, such that all variables of drug use were binary (no/yes).…”