Supplementary Table 1. Additional Characteristics of the Selected Case-Control Studies

Supplementary Table 1. Additional Characteristics of the Selected Case-Control Studies

Supplementary Table 1. Additional characteristics of the selected case-control studies for rs17878362 (TP53 PIN3) polymorphism.

Population / Study numbers and Study× / Country / Genotyping method / Mean age of cases (SD) / Mean age of controls (SD) / Adjusted method / Ref.
Indian / 1 / Jha et al., 2011 / India / Sequencing / nd* / nd* / Gender, age, BMI+, smoking status / (1)
2 / Umar et al., 2011 / India / Gel retardation / 57.3 (11.9) / 55.8 (9.4) / Gender, age / (2)
4 / Mittal et al., 2011 / India / Gel retardation / 64.4 (5.6) / 64.4 (7.1) / Gender, age / (3)
5 / Malik et al., 2011 / India / Gel retardation / 60.4 (8.4) / 58.0 (12.7) / nd* / (4)
6 / Malik et al., 2011 / India / Gel retardation / 55.9 (9.7) / 58.0 (12.7) / nd* / (4)
22 / Mitra et al., 2005 / India / Gel retardation / 55.0 (12.0) / 50.4 (11.5) / nd* / (5)
Mediterranean / 10 / de Feo et al., 2009 / Italy / Gel retardation / 66.7 (11.7) / 63.5 (13.1) / Age, alcohol consumption, family history of cancer, fruit, vegetable intake, addition of salt to meals / (6)
13 / Costa et al., 2008 / Portugal / Gel retardation / 53.4 (nd*) / 53.1 (nd*) / Age / (7)
15 / de Vecchi et al., 2008 / Italy / Gel retardation / nd* / nd* / nd* / (8)
20 / Perfumo et al., 2006 / Italy / Gel retardation / 60.1 (nd*) / 66.7 (nd*) / nd* / (9)
21 / Perfumo et al., 2006 / Italy / Gel retardation / 68.4 (nd*) / 66.7 (nd*) / nd* / (9)
23 / Gemignani et al., 2004 / Spain / Gel retardation / nd* / nd* / nd* / (10)
Northern Europe / 7 / Naccarati et al., 2010 / Czech Republic / Gel retardation / 62.2 (10.4) / 60.5 (10.7) / Gender, Age, BMI+, smoking status / (11)
8 / Polakova et al., 2009 / Czech Republic / Gel retardation / nd* / nd* / Age, sex / (12)
11 / Hrstka et al., 2009 / Czech Republic / Gel retardation / 59.7 (nd*) / 58.86 (nd*) / nd* / (13)
17 / Tan et al., 2007 / Germany / Gel retardation / 68.2 (nd*) / 66.9 (nd*) / nd* / (14)
19 / Hung et al., 2006 / Central Europe / Gel retardation / nd* / nd* / nd* / (15)
24 / Wang-Gohrke et al., 2002 / Germany / Gel retardation / nd* / nd* / nd* / (16)
United States / 12 / Gaudet et al., 2008 / USA / Gel retardation / nd* / nd* / Age / (17)
14 / Ye et al., 2008 / USA / Taqman / nd* / nd* / nd* / (18)
16 / Chen et al., 2007 / USA / Gel retardation / nd* / nd* / Age, sex, smoking status, alcohol consumption / (19)
18 / Wang et al., 2007 / USA / Gel retardation / 61.7 (11.1) / 61.4 (9.4) / nd* / (20)
25 / Wu et al., 2002 / USA / Gel retardation / 61.4 (9.7) / 60.6 (9.8) / Age, sex, smoking / (21)
Not classified / 3 / Alawadi et al., 2011 / Kuwait-Syria / Gel retardation / 48.7 (nd*) / 54.7 (nd*) / nd* / (22)
9 / Ashton et al., 2009 / Australia / Gel retardation / nd* / nd* / Age, BMI+, HBP§, diabetes, HRT#, personal history of cancer, smoking status, alcohol consumption / (23)

×: Number corresponds to Table 1, *nd: not described, +BMI: Body Mass Index, §HBP:High Blood Pressure, # HRT: Hormone replacement therapy

Supplementary Table 2. Meta-analysis results after removing all studies one by one for A1A2 and A2A2 genotypesof TP53rs17878362. The name of the study corresponds to the removed study.

A1A2 vs A1A1 genotypes / A2A2 vs A1A1 genotypes
Study Numbers and Study* / Heterogenity
P value / OR / 95% CI / Heterogenity
P value / OR / 95% CI
1 / Jha et al., 2011 / 0.03 / 1.08 / [0.99-1.19] / 0.05 / 1.47 / [1.16-1.86]
2 / Umar et al., 2011 / 0.02 / 1.08 / [0.98-1.18] / 0.05 / 1.45 / [1.15-1.85]
3 / Alawadi et al., 2011 / 0.03 / 1.07 / [0.98-1.17] / 0.15 / 1.52 / [1.27-1.82]
4 / Mittal et al., 2011 / 0.03 / 1.09 / [0.99-1.19] / 0.05 / 1.49 / [1.18-1.88]
5 / Malik et al., 2011 / 0.02 / 1.07 / [0.98-1.18] / 0.06 / 1.41 / [1.18-1.70]
6 / Malik et al., 2011 / 0.02 / 1.08 / [0.98-1.18] / 0.08 / 1.40 / [1.17-1.68]
7 / Naccarati et al., 2010 / 0.02 / 1.08 / [0.99-1.19] / 0.04 / 1.47 / [1.16-1.87]
8 / Polakova et al., 2009 / 0.02 / 1.08 / [0.98-1.18] / 0.05 / 1.46 / [1.15-1.86]
9 / Ashton et al., 2009 / 0.03 / 1.09 / [0.99-1.19] / 0.05 / 1.49 / [1.17-1.89]
10 / de Feo et al., 2009 / 0.02 / 1.08 / [0.99-1.18] / 0.04 / 1.47 / [1.16-1.87]
11 / Hrstka et al., 2009 / 0.02 / 1.07 / [0.98-1.18] / 0.04 / 1.48 / [1.17-1.88]
12 / Gaudet et al., 2008 / 0.02 / 1.09 / [0.99-1.19] / 0.05 / 1.50 / [1.18-1.91]
13 / Costa et al., 2008 / 0.02 / 1.08 / [0.98-1.18] / 0.08 / 1.42 / [1.19-1.70]
14 / Ye et al., 2008 / 0.11 / 1.10 / [1.01-1.19] / 0.10 / 1.51 / [1.26-1.82]
15 / de Vecchi et al., 2008 / 0.02 / 1.07 / [0.98-1.18] / 0.06 / 1.42 / [1.19-1.71]
16 / Chen et al., 2007 / 0.02 / 1.07 / [0.98-1.18] / 0.04 / 1.49 / [1.16-1.89]
17 / Tan et al., 2007 / 0.05 / 1.09 / [1.00-1.20] / 0.06 / 1.48 / [1.23-1.77]
18 / Wang et al., 2007 / 0.02 / 1.07 / [0.97-1.18] / 0.12 / 1.55 / [1.28-1.86]
19 / Hung et al., 2006 / 0.02 / 1.08 / [0.98-1.19] / 0.07 / 1.37 / [1.12-1.66]
20 / Perfumo et al., 2006 / 0.04 / 1.07 / [0.98-1.17] / 0.08 / 1.43 / [1.20-1.71]
21 / Perfumo et al., 2006 / 0.02 / 1.08 / [0.99-1.18] / 0.05 / 1.44 / [1.20-1.73]
22 / Mitra et al., 2005 / 0.04 / 1.09 / [1.00-1.19] / 0.14 / 1.53 / [1.27-1.83]
23 / Gemignani et al., 2004 / 0.05 / 1.06 / [0.99-1.13] / 0.04 / 1.47 / [1.16-1.87]
24 / Wang-Gohrke et al., 2002 / 0.03 / 1.07 / [0.97-1.17] / 0.05 / 1.47 / [1.15-1.87]
25 / Wu et al., 2002 / 0.12 / 1.06 / [0.99-1.13] / 0.05 / 1.43 / [1.20-1.72]

* For study number, number of cases and controls excluded and details of publications see Table I

1

Supplementary Table 3. The evolution of the meta-analysis results for rs17878362 depending on date of publication of study.

Genotype / Study / Heterogenity
P value / OR / 95% CI
A1A2 / 2005 (4 studies) / 0.01 / 1.30 / [0.94-1.78]
2006 (7 studies) / 0.01 / 1.23 / [0.99-1.52]
2007 (10 studies) / 0.01 / 1.15 / [1.00 1.33]
2008 (14 studies) / 0.01 / 1.09 / [0.96-1.23]
2009 (18 studies) / 0.01 / 1.08 / [0.97-1.20]
2010 (19 studies) / 0.01 / 1.08 / [0.97-1.19]
2011 (25 studies) / 0.03 / 1.08 / [0.99-1.18]
A2A2 / 2005 (4 studies) / 0.13 / 1.27 / [0.82-1.96]
2006 (7 studies) / 0.10 / 1.67 / [1.23-2.27]
2007 (10 studies) / 0.06 / 1.37 / [1.07 1.76]
2008 (14 studies) / 0.03 / 1.41 / [1.03-1.94]
2009 (18 studies) / 0.10 / 1.40 / [1.14-1.71]
2010 (19 studies) / 0.13 / 1.40 / [1.15-1.71]
2011 (25 studies) / 0.06 / 1.45 / [1.22-1.74]

Supplementary Table 4. Meta-analysis results for rs1042522 (TP53 PEX4)and rs1625895 (TP53 PIN6) polymorphisms in the selected case-control studies following Hardy-Weinberg equilibrium.

Genotypes / Cases
n (%) / Controls
n (%) / Heterogenity
P value / OR / [95% CI] / P trend#
Overall
rs1042522(Study numbers: 1, 3, 4, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25; MAF = 0.29)
Total / 8 517 (100.0) / 9 311 (100.0)
R72/R72 / 4 227 (49.6) / 4 833 (51.9) / 1.00 / - / <0.01
R72/P72 / 3 340 (39.3) / 3 586 (38.5) / <0.01* / 1.16 / [1.05-1.18]
P72/P72 / 950 (11.1) / 892 (9.6) / 0.02+ / 1.06 / [0.91-1.24]
rs1625895 (Study numbers: 4, 9, 10, 11, 12, 14, 16, 18, 24, 25; MAF = 0.19)
Total / 5 011 (100.0) / 5 100 (100.0)
GG / 3 180 (63.5) / 3 522 (69.1) / 1.00 / -
GA / 1 312 (26.2) / 1 192 (23.4) / 0.01* / 1.19 / [1.02-1.40] / <0.01
AA / 519 (10.3) / 386 (7.5) / 0.46* / 1.19 / [0.89-1.60]

1

Supplementary Table 5: Haplotype distributions for rs17878362*, rs1042522 and rs1625895 in 261DNA samples from three HapMap populations (African: Nigeria (90 individuals); Asian: China (81 individuals) and Caucasian: Northern or Western European (90 individuals)) based on published data (24).

Polymorphisms / African
(%) / Asian
(%) / Caucasian
(%)
rs17878362* / rs1042522 / rs1625895
A1 / R72 / G / 31.67 / 53.70 / 78.13
A1 / P72 / G / 38.33 / 43.83 / 11.46
A1 / R72 / A / - / - / 0.52
A1 / P72 / A / 3.89 / 0.62 / 0.52
A2 / R72 / G / - / - / -
A2 / P72 / G / - / - / -
A2 / R72 / A / - / - / -
A2 / P72 / A / 26.11 / 1.85 / 9.37%

*tagged by rs2909430

REFERENCES

1.Jha P, Jha P, Pathak P, Chosdol K, Suri V, Sharma MC, et al. TP53 polymorphisms in gliomas from Indian patients: Study of codon 72 genotype, rs1642785, rs1800370 and 16 base pair insertion in intron-3. Experimental and molecular pathology 2011 Apr; 90(2): 167-172.

2.Umar M, Upadhyay R, Khurana R, Kumar S, Ghoshal UC, Mittal B. Role of p53 and p73 genes polymorphisms in susceptibility to esophageal cancer: a case control study in a northern Indian population. Molecular biology reports 2012 Feb; 39(2): 1153-1162.

3.Mittal RD, George GP, Mishra J, Mittal T, Kapoor R. Role of functional polymorphisms of P53 and P73 genes with the risk of prostate cancer in a case-control study from Northern India. Archives of medical research 2011 Feb; 42(2): 122-127.

4.Malik MA, Sharma K, Goel S, Zargar SA, Mittal B. Association of TP53 intron 3, 16 bp duplication polymorphism with esophageal and gastric cancer susceptibility in Kashmir Valley. Oncology research 2011; 19(3-4): 165-169.

5.Mitra S, Sikdar N, Misra C, Gupta S, Paul RR, Roy B, et al. Risk assessment of p53 genotypes and haplotypes in tobacco-associated leukoplakia and oral cancer patients from eastern Idia. International journal of cancer Journal international du cancer 2005 Dec 10; 117(5): 786-793.

6.De Feo E, Persiani R, La Greca A, Amore R, Arzani D, Rausei S, et al. A case-control study on the effect of p53 and p73 gene polymorphisms on gastric cancer risk and progression. Mutation research 2009 Apr 30; 675(1-2): 60-65.

7.Costa S, Pinto D, Pereira D, Rodrigues H, Cameselle-Teijeiro J, Medeiros R, et al. Importance of TP53 codon 72 and intron 3 duplication 16bp polymorphisms in prediction of susceptibility on breast cancer. BMC cancer 2008; 8: 32.

8.De Vecchi G, Verderio P, Pizzamiglio S, Manoukian S, Bernard L, Pensotti V, et al. The p53 Arg72Pro and Ins16bp polymorphisms and their haplotypes are not associated with breast cancer risk in BRCA-mutation negative familial cases. Cancer detection and prevention 2008; 32(2): 140-143.

9.Perfumo C, Bonelli L, Menichini P, Inga A, Gismondi V, Ciferri E, et al. Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2-Pro72 haplotype. Digestion 2006; 74(3-4): 228-235.

10.Gemignani F, Moreno V, Landi S, Moullan N, Chabrier A, Gutierrez-Enriquez S, et al. A TP53 polymorphism is associated with increased risk of colorectal cancer and with reduced levels of TP53 mRNA. Oncogene 2004 Mar 11; 23(10): 1954-1956.

11.Naccarati A, Pardini B, Polakova V, Smerhovsky Z, Vodickova L, Soucek P, et al. Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: an association study in the Czech Republic. Carcinogenesis 2010 Apr; 31(4): 666-670.

12.Polakova V, Pardini B, Naccarati A, Landi S, Slyskova J, Novotny J, et al. Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic. Human mutation 2009 Apr; 30(4): 661-668.

13.Hrstka R, Beranek M, Klocova K, Nenutil R, Vojtesek B. Intronic polymorphisms in TP53 indicate lymph node metastasis in breast cancer. Oncology reports 2009 Nov; 22(5): 1205-1211.

14.Tan XL, Nieters A, Hoffmeister M, Beckmann L, Brenner H, Chang-Claude J. Genetic polymorphisms in TP53, nonsteroidal anti-inflammatory drugs and the risk of colorectal cancer: evidence for gene-environment interaction? Pharmacogenetics and genomics 2007 Aug; 17(8): 639-645.

15.Hung RJ, Boffetta P, Canzian F, Moullan N, Szeszenia-Dabrowska N, Zaridze D, et al. Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case-control study in Central Europe. Cancer research 2006 Aug 15; 66(16): 8280-8286.

16.Wang-Gohrke S, Becher H, Kreienberg R, Runnebaum IB, Chang-Claude J. Intron 3 16 bp duplication polymorphism of p53 is associated with an increased risk for breast cancer by the age of 50 years. Pharmacogenetics 2002 Apr; 12(3): 269-272.

17.Gaudet MM, Gammon MD, Bensen JT, Sagiv SK, Shantakumar S, Teitelbaum SL, et al. Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York. Breast cancer research and treatment 2008 Mar; 108(1): 93-99.

18.Ye Y, Yang H, Grossman HB, Dinney C, Wu X, Gu J. Genetic variants in cell cycle control pathway confer susceptibility to bladder cancer. Cancer 2008 Jun; 112(11): 2467-2474.

19.Chen K, Hu Z, Wang LE, Zhang W, El-Naggar AK, Sturgis EM, et al. Polymorphic TP53BP1 and TP53 gene interactions associated with risk of squamous cell carcinoma of the head and neck. Clinical cancer research : an official journal of the American Association for Cancer Research 2007 Jul 15; 13(14): 4300-4305.

20.Wang W, Spitz MR, Yang H, Lu C, Stewart DJ, Wu X. Genetic variants in cell cycle control pathway confer susceptibility to lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2007 Oct 1; 13(19): 5974-5981.

21.Wu X, Zhao H, Amos CI, Shete S, Makan N, Hong WK, et al. p53 Genotypes and Haplotypes Associated With Lung Cancer Susceptibility and Ethnicity. Journal of the National Cancer Institute 2002 May 1; 94(9): 681-690.

22.Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N, et al. P53 gene polymorphisms and breast cancer risk in Arab women. Med Oncol 2011 Sep; 28(3): 709-715.

23.Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, et al. Polymorphisms in TP53 and MDM2 combined are associated with high grade endometrial cancer. Gynecologic oncology 2009 Apr; 113(1): 109-114.

24.Garritano S, Gemignani F, Palmero EI, Olivier M, Martel-Planche G, Le Calvez-Kelm F, et al. Detailed haplotype analysis at the TP53 locus in p.R337H mutation carriers in the population of Southern Brazil: evidence for a founder effect. Human mutation 2010 Feb; 31(2): 143-150.

1