UNIVERSITÁ DI PISA
Corso di Dottorato in
Microbiologia e Genetica
Presidente Prof. Mario Campa
Genetic susceptibility and pharmacogenetics
of Multiple Myeloma
Candidate Supervisor
Alessandro Martino Prof.ssa Anna Maria Rossi
Anno accademico 2010/2011 SSD MED/07
Genetic Susceptibility and Pharmacogenetics of Multiple Myeloma
I
I
NDEXAbstract III
(1) Introduction: Multiple Myeloma 5
1.1) General overview 5
1.2) Pathogenesis: a multistep process 5
1.3) Genetic features 7
1.4) Treatments, prognosis and survival 9
1.5) Study of SNPs in Multiple Myeloma risk 10
1.6) Study of SNPs in Multiple Myeloma pharmacogenetics 12
(2) Aim & Scope 14
(3) Role of polymorphisms of interleukin IL1B, IL2, IL6, TNF-α, IL1R1, IL2RB, IL6R and
TNFRSF1B genes in Multiple Myeloma 15
3.1) Introduction 15
3.2) Material and methods 16
3.2.1) Study population 16
3.2.2) SNP selection and genotyping 18
3.2.3) Statistical analysis 19
3.3) Results 20
3.4) Conclusion and discussion 27
(4) Polymorphisms in xenobiotic transporter genes ABCB1, ABCG2, ABCC2, ABCC1 and ABCC3 and Multiple Myeloma Risk: a case-control study in the context of the
IMMEnSE (International Multiple Myeloma rESEarch) consortium 30
4.1) Introduction 30
4.2) Material and methods 31
4.2.1) Study population: The International Multiple Myeloma rESEarch
(IMMEnSE) consortium 31
4.2.2) SNP selection 33
4.2.3) Sample preparation and genotyping 34
4.2.4) Statistical analysis 37
4.3) Results 38
4.3.1) Replication 49
4.4) Conclusion and discussion 51
(5) Polymorphisms in xenobiotic transporter genes ABCB1, ABCG2, ABCC2, ABCC1 and ABCC3 and Multiple Myeloma Risk: a case-control study in the context of the
IMMEnSE (International Multiple Myeloma rESEarch) consortium 52
5.1) Introduction 52
5.2) Material and methods 53
5.3) Results 55
Genetic Susceptibility and Pharmacogenetics of Multiple Myeloma
II
(6) Conclusion and future perspectives 59
(7) Acknowledgements 61
