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Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking.

ABSTRACT: Abstract t(14;18)-positive cells can be detected not only in patients with follicular lymphoma (FL) but also in healthy individuals (HIs). We used epidemiological data and blood samples of the population-based Study of Health in Pomerania (SHIP) to analyze associations of FL risk factors and t(14;18)-positive cells in HIs. Buffy coat samples from 4152 study participants were tested by real-time polymerase chain reaction (PCR) for t(14;18)-positive cells. Of 3966 evaluable subjects, 1526 were t(14;18)-PCR positive [38.5%, median 3.9 t(14;18)-positive per million nucleated cells, range 0.6-9299]. In multivariable analyses, age and sex but not parameters of smoking exposure were significantly associated with t(14;18) prevalence (logistic regression, p < 0.001). Multivariable analyses of t(14;18)-frequency showed a positive association with age but not with sex or smoking. These age and sex associations in HIs require careful control in future studies of t(14;18) as a potential biomarker of lymphoma risk.

SUBMITTER: Hirt C

PROVIDER: S-EPMC4444076 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking.

Hirt Carsten C Weitmann Kerstin K Schüler Frank F Kiefer Thomas T Rabkin Charles S CS Hoffmann Wolfgang W Dölken Gottfried G

Leukemia & lymphoma 20130507 12

Abstract t(14;18)-positive cells can be detected not only in patients with follicular lymphoma (FL) but also in healthy individuals (HIs). We used epidemiological data and blood samples of the population-based Study of Health in Pomerania (SHIP) to analyze associations of FL risk factors and t(14;18)-positive cells in HIs. Buffy coat samples from 4152 study participants were tested by real-time polymerase chain reaction (PCR) for t(14;18)-positive cells. Of 3966 evaluable subjects, 1526 were t(1 ...[more]

PMID: 23527525

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Project description:PurposeThe t(14;18) translocation might represent an intermediate step in the pathogenesis of follicular lymphoma (FL), one of the most common subtypes of non-Hodgkin lymphoma. Circulating t(14;18)-positive cells can also be detected in 30-60 % of healthy individuals at low frequencies. Some studies found a negative association between reproductive factors or use of menopausal hormone therapy (MHT) with FL. The objective of this study was to evaluate whether there is an association between number of frequencies, oral contraceptive (OC) use, menopausal status and MHT, and t(14;18) prevalence and frequency in a representative population analysis based on an epidemiologic study in the northeastern part of Germany.MethodsThe analysis is based on results of buffy coat samples from 1,981 women of the Study of Health in Pomerania (SHIP-0) and data obtained in standardized face-to-face interviews. For prevalence, odds ratios (OR) and 95 % confidence intervals (CI) were calculated using unconditional logistic regression. Frequency data were analyzed using negative binomial regression. The multivariable models included age, number of pregnancies, menopausal status (premenopausal, natural, medical/surgical menopause), OC use and MHT as a measure for exogenous hormone exposure use.ResultsWe found no association between reproductive history and combined exogenous hormone use on the prevalence of circulating t(14;18)-positive cells. Modeling MHT and OC use separately in a sensitivity analysis, the MHT parameter yielded statistical significance [OR 1.37 (95 % CI 1.04;1.81)]. t(14;18) frequency was associated with use of OC [incidence rate ratio (IRR) for ever use 3.18 (95 % CI 1.54;6.54)], current use [IRR 3.86 (1.56;9.54)], >10 years use [IRR 3.93 (1.67;9.23)] and MHT [restricted to postmenopausal women; IRR 2.63 (95 % CI 1.01;6.85)] in bivariate age-adjusted analyses. In the multivariable model, medical/surgical menopause [IRR 2.46 (1.11;5.44)] and the category ever use of OC and MHT were statistically significant [IRR 2.41 (1.09;5.33)].ConclusionsExogenous hormone use might be a risk factor for t(14;18) frequency rather than for t(14;18) prevalence. Further research on healthy individuals carrying a t(14;18) translocation and possible risk factors for malignant lymphoma is necessary to determine the additional molecular or immunological events that have to occur to develop FL.

Project description:BACKGROUND:Circulating FGF21 levels are commonly elevated in disease states. There is limited information regarding concentrations of circulating FGF21 in the absence of disease, as well as age-related differences in body composition that may contribute to FGF21 regulation across groups. OBJECTIVE:The objectives of this study were to assess FGF21 levels across age groups (childhood to elder adulthood), and investigate whether body composition indices are associated with age-related differences in circulating FGF21. MATERIALS AND METHODS:We cross-sectionally analyzed serum concentrations of FGF21 in 184 healthy subjects aged 5-80y (45% male). Multiple linear regression was performed to assess the independent association of categorical age (children: 5-12y, young adults: 20-29y, adults: 30-50y, older adults: 55-64y, elder adults: 65-80y) with FGF21 concentration taking into account DXA-measured body composition indices [bone mineral density (BMD) and percent lean, trunk, and fat mass]. We also stratified analysis by tertile of FGF21. RESULTS:Incremental increases in FGF21 levels were observed across age groups (youngest to highest). Age group was positively associated with FGF21 level independent of body composition indices (age group variable: β=0.25, 0.24, 0.24, 0.23, all P<0.0001, controlling for percent lean, BMD, percent fat, and percent trunk fat, respectively). By FGF21 tertile, age group was associated with FGF21 in the lowest tertile only (β=13.1, 0.19, 0.18, all P≤0.01, accounting for percent lean, fat and trunk fat, respectively), but not when accounting for BMD. CONCLUSIONS:Our findings in a healthy population display an age-related increase in serum FGF21, highlighting a potential age effect in response to metabolic demand over the lifecourse. FGF21 levels increase with age independently of body composition. At lower levels of FGF21, BMD, but not other body composition parameters, attenuates the association between FGF21 level and age, suggesting the metabolic demand of the skeleton may provide a link between FGF21 and energy metabolism.

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Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking.

Publications

Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking.

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