Summary:
This thesis encompassed three studies: an original cohort study, examining the
survival of multiple myeloma (MM) patients, a meta-analysis and a systematic
review of meta-analyses.
The cohort study aimed to evaluate the potential prognostic role of cytogenetic
events, as well as their combinations, in terms of overall survival in a large
cohort of unselected MM patients (n=432). Multivariate Cox regression analysis
was performed, adjusting for age, gender, CKD-EPI KDIGO classification,
International Staging System, ECOG performance status, serum LDH, serum
calcium, platelet count and blood hemoglobin. The presence of del(13q)
(adjusted HR=1.71, 95%CI:1.18-2.47), t(4;14) (adjusted HR=2.00, 95%CI:
1.19-3.35) and del(17p) (adjusted HR=2.03, 95%CI: 1.22-3.37) was independently
associated with poorer overall survival. The poor prognosis seemed more
pronounced among patients harboring combinations of two adverse cytogenetic
abnormalities. On the contrary, t(14;16), t(11;14) and add(1q21) were not
associated with overall survival. The effect of bortezomib seemed rather
minimal in the modification of the prognostic role mediated by del(17p). The
cohort study concluded that del(13q), t(4;14) and del(17p) seem to represent
independent poor prognostic factors for patients with MM.
The meta-analysis aimed to examine the association between alcohol consumption
and MM risk. Eligible publications were sought in PubMed up to December 31,
2013. Separate analyses were performed by study design, gender, alcoholic
beverages and levels of consumption. 16 case-control studies (3,921 cases and
19,594 controls) and 10 cohort studies (3,167 incident cases in a total cohort
of 2,557,649 subjects) were eligible. Ever consumption of alcohol was
associated with reduced MM risk (pooled RR=0.88, 95%CI: 0.79-0.99) and
especially consumption of wine correlated with reduced MM risk (pooled RR=0.77,
95%CI: 0.67-0.89 for ever drinkers). MM risk was not affected by beer or liquor
intake. A protective association was observed among females (pooled RR=0.79,
95%CI: 0.69-0.89 for ever drinkers), whereas the association among males seemed
null. The meta-analysis concluded that, contrary to most solid tumors, alcohol
intake may confer protection in terms of MM risk among females, with wine being
particularly beneficial.
The systematic review of meta-analyses aimed to synthesize meta-analyses
examining risk factors for MM, so as to provide a comprehensive, parsimonious
summary of the current evidence. Eligible meta-analyses were sought in PubMed
adopting a predefined algorithm, without any restriction of publication
language; end-of-search date was October 10, 2014. Among the 22 ultimately
included meta-analyses, nine examined occupational factors, four assessed
aspects of lifestyle (smoking, alcohol, BMI), five evaluated the presence of
other diseases, whereas four addressed genetic factors as potential risk
factors of MM. A vast compendium of significant associations arose, including
farming, occupation as a firefighter, occupation as a hairdresser, exposures to
chemicals or pesticides, overweight and obesity, patterns of alcohol intake,
pernicious anemia, ankylosing spondylitis, gene promoter methylation and
polymorphisms. The systematic review of meta-analyses concluded that MM is a
multifactorial disease, encompassing a wide variety of risk factors which span
numerous life aspects. Further accumulation of evidence through meta-analyses
is anticipated in this rapidly growing field of Epidemiology.
