Supplementary Material

Adiposity is associated with p53 gene mutations in breast cancer

Breast Cancer Research and Treatment

Heather M. Ochs-Balcom1*, Catalin Marian2,3*†, Jing Nie1, Theodore M. Brasky2,David S. Goerlitz4, Maurizio Trevisan1,6, Stephen B. Edge5, Janet Winston5, Deborah L. Berry4, Bhaskar V. Kallakury4, Jo L. Freudenheim1, and Peter G. Shields2

1Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY

2OhioStateUniversityComprehensiveCancerCenter, The OhioStateUniversity, Columbus, OH

3Biochemistry Department, "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania

4LombardiCancerCenter, Georgetown University, Washington, DC

5Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY

6Department of Community Health and Social Medicine, School of Biomedical Education, The CityCollege of New York, New York, New York, USA

*These authors contributed equally to the study.

†Corresponding Author

Catalin Marian, MD PhD

Email: ;

Phone: 614-366-2955

Fax: 614-292-0517

Supplementary Table 1. Characteristics of breast cancer cases according to p53 mutation type (all, & by type/effect), WEB Study, 1996-2001.
Characteristics / P53- / P53+
(All) / P53+, by Mutation Type / P53+, by Mutation Effect
Transitions / Transversions / Frameshift / Missense / Nonsense / Silent / Splice
N / 528 / 205 / 137 / 58 / 10 / 147 / 15 / 27 / 6
Race, % white / 92.2 / 92.2 / 94.9 / 84.5* / 100.0 / 92.5 / 86.7 / 96.3 / 66.7*
Age, yr / 57.3 (11.3) / 56.6 (11.7) / 56.1 (11.8) / 57.5 (11.7) / 57.9 (11.9) / 55.8 (11.9) / 58.0 (13.6) / 57.7 (10.1) / 64.0 (10.3)
Education, yr / 13.6 (2.6) / 13.6 (2.3) / 13.7 (2.2) / 13.4 (2.3) / 14.2 (2.6) / 13.5 (2.3) / 14.4 (2.6) / 13.9 (1.9) / 12.3 (0.5)*
Body mass index, kg/m2 / 28.0 (6.2) / 29.5 (7.3)* / 29.4 (7.4)* / 29.6 (7.6) / 30.8 (4.7) / 29.4 (7.6)* / 30.5 (6.8) / 29.0 (7.0) / 31.2 (8.0)
Waist circumference, cm / 88.9(15.8) (n=516) / 91.1(14.1)
(n=201) / 90.6(13.8)
(n=135) / 91.9(15.2)
(n=56) / 94.7(10.8) / 91.1(14.8)
(n=145) / 93.0(12.7) / 89.3(12.8)
(n=26) / 88.3(8.3)
(n=5)
Waist-to-hip ratio / 0.8(0.1)
(n=514) / 0.8(0.1)
(n=200) / 0.8(0.1)
(n=134) / 0.8(0.1)
(n=56) / 0.9(0.1)* / 0.8(0.1)
(n=144) / 0.9(0.1) / 0.8(0.1)
(n=26) / 0.8(0.1)
(n=5)
Premenopausal / 30.7 / 33.7 / 35.0 / 31.0 / 30.0 / 38.1 / 26.7 / 18.5 / 16.7
Postmenopausal / 69.3 / 66.3 / 65.0 / 69.0 / 70.0 / 61.9 / 73.3 / 81.5 / 83.3
Nulliparous, % / 17.6 / 17.6 / 16.8 / 17.2 / 30.0 / 14.3 / 26.7 / 25.9 / 16.7
Age at menarche, yr / 12.5 (1.6) / 12.6 (1.7) / 12.7 (1.6) / 12.7 (1.9) / 12.1 (1.5) / 12.7 (1.8) / 13.2 (1.2) / 12.2 (1.5) / 12.7 (1.6)
Number of births / 2.3 (1.7) / 2.3 (1.7) / 2.3 (1.7) / 2.5 (1.7) / 1.7 (1.3) / 2.4 (1.7) / 1.9 (1.2) / 2.2 (2.0) / 3.0 (1.5)
First-degree relative with breast cancer, % yes / 22.0
(n=491) / 18.4
(n=190) / 17.5
(n=126) / 20.4
(n=54) / 20.0 / 20.1
(n=134) / 14.3
(n=14) / 15.4
(n=26) / 0.0
Previous benign breast disease, % yes / 35.8
(n=517) / 32.3
(n=201) / 33.8
(n=133) / 25.9 / 50.0 / 30.3
(n=145) / 35.7
(n=14) / 38.5
(n=26) / 16.7
Tumor size, cm / 1.8 (1.2)
(n=482) / 1.9 (1.2)
(n=184) / 1.9 (1.2)
(n=123) / 2.0 (1.4)
(n=53) / 1.6 (0.8)
(n=8) / 2.1 (1.3)*
(n=130) / 2.2 (1.4) / 1.2 (0.6)*
(n=25) / 1.8 (0.5)
Metastatic disease at presentation, % yes / (n=500)
27.8 / (n=192)
30.2 / (n=129)
28.7 / (n=53)
30.2 / 50.0 / (n=137)
28.5 / (n=14)
35.7 / (n=25)
32.0 / 16.7
Lymph node involvement, % yes / (n=490)
28.8 / (n=190)
31.6 / (n=127)
29.9 / (n=53)
30.2 / *
60.0 / (n=136)
28.7 / (n=13)
46.2 / (n=25)
32.0 / 16.7
Histologic grade / (n=423) / (n=160)* / (n=105)* / (n=47) / (n=8) / (n=114)* / (n=13) / (n=20) / (n=5)
Well / 13.9 / 8.8 / 9.5 / 8.5 / 0.0 / 8.8 / 7.7 / 15.0 / 0.0
Moderate / 40.4 / 26.3 / 23.8 / 29.8 / 37.5 / 21.9 / 23.1 / 50.0 / 20.0
Poorly / 45.6 / 65.0 / 66.7 / 61.7 / 62.5 / 69.3 / 69.2 / 35.0 / 80.0
Nuclear grade / (n=467) / (n=184)* / (n=121)* / (n=53)* / (n=130)* / (n=14)* / (n=24)
I / 19.5 / 15.8 / 17.4 / 15.1 / 0.0 / 13.1 / 14.3 / 33.3 / 33.3
II / 42.6 / 23.9 / 22.3 / 26.4 / 30.0 / 23.8 / 14.3 / 29.2 / 16.7
III / 37.9 / 60.3 / 60.3 / 58.5 / 70.0 / 63.1 / 71.4 / 37.5 / 50.0
TNM stage / (n=416) / (n=161) / (n=106) / (n=47) / (n=8) / (n=115) / (n=12)* / (n=20)
I / 53.6 / 45.3 / 47.2 / 44.7 / 25.0 / 46.1 / 16.7 / 60.0 / 66.7
IIa/ IIb / 39.4 / 46.0 / 47.2 / 42.6 / 50.0 / 46.1 / 66.7 / 35.0 / 33.3
III/ IV / 7.0 / 8.7 / 5.7 / 12.8 / 25.0 / 7.8 / 16.7 / 5.0 / 0.0
ER, % positive / 72.8
(n=525) / 60.8*
(n=204) / 60.6* / 65.5 / 33.3*
(n=9) / 61.2* / 46.7* / 77.8 / 50.0
PR, % positive / 67.7
(n=520) / 52.2*
(n=201) / 54.8*
(n=135) / 50.0*
(n=56) / 30.0* / 51.0*
(n=145) / 33.3* / 76.0
(n=25) / 66.7
HER2, % positive / 9.0
(n=432) / 12.6
(n=174) / 12.1
(n=116) / 13.7
(n=51) / 14.3
(n=7) / 13.8
(n=123) / 14.3
(n=14) / 4.2
(n=24) / 16.7
Molecular Subtype (%)** /
(n=430) / *
(n=172) / *
(n=116) / (n=50) / *
(n=6) / *
(n=123) / *
(n=14) / (n=23)
Luminal A / 76.5 / 61.0 / 61.2 / 64.0 / 33.3 / 59.3 / 42.9 / 91.3 / 50.0
Luminal B / 4.7 / 7.6 / 6.9 / 8.0 / 16.7 / 7.3 / 14.3 / 0.0 / 16.7
HER2 expressing / 4.2 / 5.2 / 5.2 / 6.0 / 0.0 / 6.5 / 0.0 / 4.3 / 0.0
Triple negative / 14.7 / 26.2 / 26.7 / 22.0 / 50.0 / 26.8 / 42.9 / 4.3 / 33.3
Ki67, % positive** / 9.2
(n=491) / 15.6*
(n=192) / 14.3
(n=126) / 17.9*
(n=56) / 20.0 / 15.6*
(n=135) / 6.7 / 14.8 / 40.0*
(n=5)
Smoking status (%) / (n=527) / (n=204) / (n=57) / (n=146)
Never / 44.0 / 47.1 / 43.8 / 54.4 / 50.0 / 45.2 / 53.3 / 48.1 / 66.7
Former / 43.6 / 38.2 / 40.9 / 33.3 / 30.0 / 38.4 / 40.0 / 44.4 / 16.7
Current / 12.3 / 14.7 / 15.3 / 12.3 / 20.0 / 16.4 / 6.7 / 7.4 / 16.7
*Differences statistically significant compared to p53 negative cases.
**Luminal A: ER+ or PR+, HER2-; Luminal B: ER+ or PR+, HER2+; HER2 Expressing: ER-/PR-, HER2+; Triple-negative: ER-/PR-/HER2-.
Supplementary Table 2. Association of p53 mutations with breast cancer risk factors. WEB Study, 1996-2001.
Characteristic / p53 positive / Trans-itions / Trans-versions / p53
negative / OR (95% CI)*
p53 positive vs. p53 negative / Transitions vs. p53 negative / Transversions vs.
p53 negative
Race
Non-Whites / 16 / 7 / 9 / 41 / 1.00 / 1.00 / 1.00
Whites / 189 / 130 / 49 / 487 / 1.01 (0.55-1.86) / 1.62 (0.71-3.70) / 0.46 (0.21-1.01)
Age
≤51 / 80 / 55 / 22 / 185 / 1.00 / 1.00 / 1.00
52-66 / 74 / 50 / 19 / 201 / 0.84 (0.47-1.49) / 0.83 (0.43-1.60) / 0.75 (0.29-1.96)
>66 / 51 / 32 / 17 / 142 / 0.82 (0.43-1.54) / 0.76 (0.36-1.59) / 0.91 (0.33-2.56)
p for trend / 0.74 / 0.52 / 0.80
Education
≤12 / 96 / 63 / 28 / 222 / 1.00 / 1.00 / 1.00
13-14 / 51 / 33 / 17 / 162 / 0.69 (0.46-1.04) / 0.66 (0.41-1.07) / 0.86 (0.45-1.64)
>14 / 58 / 41 / 13 / 144 / 0.89 (0.60-1.33) / 0.94 (0.59-1.49) / 0.73 (0.36-1.49)
p for trend / 0.97 / 0.92 / 0.63
Number of births
0-2 / 121 / 86 / 27 / 324 / 1.00 / 1.00 / 1.00
3 / 45 / 27 / 17 / 106 / 1.17 (0.77-1.76) / 0.99 (0.61-1.62) / 2.00 (1.03-3.86)
>3 / 39 / 24 / 14 / 98 / 1.13 (0.72-1.78) / 1.00 (0.59-1.71) / 1.79 (0.87-3.70)
p for trend / 0.51 / 0.61 / 0.36
Age at first birth
No child / 36 / 23 / 10 / 93 / 1.00 / 1.00 / 1.00
≤23 / 88 / 57 / 28 / 218 / 1.06 (0.66-1.70) / 1.08 (0.61-1.90) / 1.19 (0.54-2.62)
>23 / 81 / 57 / 20 / 217 / 0.96 (0.60-1.53) / 1.05 (0.61-1.82) / 0.88 (0.39-1.97)
Age at menarche
≤12 / 96 / 60 / 29 / 264 / 1.00 / 1.00 / 1.00
13 / 57 / 42 / 14 / 145 / 1.09 (0.74-1.60) / 1.29 (0.82-2.00) / 0.90 (0.46-1.76)
>13 / 52 / 35 / 15 / 119 / 1.21 (0.81-1.81) / 1.34 (0.83-2.15) / 1.11 (0.57-2.17)
p for trend / 0.38 / 0.40 / 0.41
Family history of breast cancer
No / 155 / 104 / 43 / 383 / 1.00 / 1.00 / 1.00
Yes / 35 / 22 / 11 / 108 / 0.80 (0.52-1.22) / 0.74 (0.44-1.22) / 0.95 (0.47-1.91)
Previous benign breast disease
No / 136 / 88 / 43 / 332 / 1.00 / 1.00 / 1.00
Yes / 65 / 45 / 15 / 185 / 0.85 (0.60-1.20) / 0.88 (0.59-1.32) / 0.66 (0.36-1.23)
Smoking status
Never / 96 / 60 / 31 / 232 / 1.00 / 1.00 / 1.00
Former / 78 / 56 / 19 / 230 / 0.82 (0.58-1.17) / 0.94 (0.63-1.42) / 0.63 (0.35-1.16)
Current / 30 / 21 / 7 / 65 / 1.12 (0.67-1.88) / 1.33 (0.73-2.42) / 0.70 (0.28-1.74)
Drinking status
Never drinker / 34 / 21 / 12 / 84 / 1.00 / 1.00 / 1.00
Ever drinker / 170 / 115 / 46 / 440 / 0.92 (0.59-1.45) / 0.97 (0.57-1.65) / 0.81 (0.40-1.62)
*Odds ratios and 95% confidence intervals adjusted for age, education, race, and menopausal status