Endocrine Abstracts (2002) 3 P128

Cigarette smoking exposure, serum insulin-like growth factors, and cancer risk: A population-based study

AG Renehan1,2, H Gleeson2, WS Atkin3, ST O'Dwyer1 & SM Shalet2

1Department of Surgery, Christie Hospital NHS Trust, Manchester, UK; 2Department of Endocrinology, Christie Hospital NHS Trust, Manchester, UK; 3ICRF, St Mark's Colorectal Unit, London, UK.

BACKGROUND We examined the relationship between cigarette smoking exposure and serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in a broad-based population, as both smoking and changes in the IGF/IGFBP system have been implicated as risk factors for common epithelial cancers.

METHODS Blood was collected from 442 unselected individuals (M, 232: F, 210) attending the Flexi-Scope colorectal cancer screening trial. All individuals were healthy and aged 55-64 years. Cigarette exposure was determined using a validated questionnaire. Statistical analyses were based on (i) current versus never smokers, and (ii) ex-smokers versus never smokers. Univariate comparisons of means used t-tests and 1-ANOVA. Multivariate models were constructed using general factorial analysis of variance mutually adjusting for IGF-I and IGFBP-3.

RESULTS By univariate and multivariate analyses, there were no significant differences in mean serum IGF-I, IGF-II and IGFBP-2 levels for current smokers versus never smokers, and ex-smokers versus never smokers. By contrast, among male current smokers, mean IGFBP-3 levels were significantly lower compared with never and ex-smokers [mean(SD): 2.91(0.62) versus 3.19(0.55), 3.08(0.66) micrograms/litre]. Adjustment for age, BMI and HRT usage, confirmed that mean differences in IGFBP-3 values were significantly reduced in current smokers, and furthermore, demonstrated that these reductions were related in a stepwise manner to duration of smoking, number of cigarette per day, and pack-years of smoking. Reductions in means were significant for both males (all P < 0.0001) and females (all P < 0.001). Among male ex-smokers, cessation of smoking before the age of 45 years was associated with normalisation of serum IGFBP-3 levels, but for males who quit smoking after 45 years, mean IGFBP-3 values remained significantly reduced.

CONCLUSIONS Current cigarette smoking is associated with significant exposure-related reductions in mean serum IGFBP-3 levels. As lower IGFBP-3 levels may favour tumour growth through reduced apoptosis and/or increased availability of IGF-I, these findings offer an alternative mechanism for smoking-related cancer development.

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