NIH Public Access Author Manuscript Int J Cancer. Author manuscript; available in PMC 2012 December 15.

NIH-PA Author Manuscript

Published in final edited form as: Int J Cancer. 2011 December 15; 129(12): 2875–2884. doi:10.1002/ijc.25959.

Body mass index and body size in early adulthood and risk of pancreatic cancer in a central European multicenter case-control study Kevin Y. Urayama1, Ivana Holcatova2, Vladimir Janout3, Lenka Foretova4, Eleonora Fabianova5, Zora Adamcakova5, Miroslav Ryska6, Arnost Martinek7, Olga Shonova8, Paul Brennan1, and Ghislaine Scélo1,* 1International Agency for Research on Cancer (IARC), Lyon, France 2Charles

University in Prague, 1st Faculty of Medicine, Institute of Hygiene and Epidemiology, Prague, Czech Republic 3Palacky

University, Faculty of Medicine, Department of Preventive Medicine, Olomouc, Czech

NIH-PA Author Manuscript

Republic 4Masaryk

Memorial Cancer Institute, Department of Cancer Epidemiology and Genetics, Brno, Czech Republic 5Regional

Authority of Public Health in Banská Bystrica, Slovakia

6Central

Military Hospital, Prague, Czech Republic

7Faculty

of Health Studies Ostrava, Ostrava, Czech Republic

8Gastroenterology

Department of Regional Hospital, Ceske Budejovice, Czech Republic

Abstract

NIH-PA Author Manuscript

The relationship between two measures of excess body weight, body mass index (BMI) and body size score, and risk of pancreatic cancer was examined among 574 pancreatic cancer cases and 596 frequency-matched controls from the Czech Republic and Slovakia enrolled between 2004 and 2009. Analyses using multivariable logistic regression showed an increased risk of pancreatic cancer associated with elevated quartiles of BMI at ages 20 [fourth quartile: odds ratio (OR) = 1.79, 95% confidence interval (CI): 1.23, 2.61] and 40 (fourth quartile: OR = 1.57, 95% CI: 1.09, 2.27) compared to the lowest quartile. Consistent results were observed for body size score at ages 20 (high versus low: OR = 1.66, 95% CI: 1.08, 2.57) and 40 (medium versus low: OR = 1.36, 95% CI: 1.00, 1.86), but no association was found for BMI and body size score at two years prior to interview. Stronger risk estimates for BMI were observed in males than females, particularly at age 20, but the analysis of body size yielded similar estimates by sex. When considering excess body weight at both ages 20 and 40 jointly, the highest risk estimates were observed among subjects with elevated levels at both time periods in the analysis of BMI (OR=1.86, 95% CI: 1.32, 2.62) and body size (OR=1.53, 95% CI: 1.09, 2.13). These findings, based on two different measures, provide strong support for an increased risk of pancreatic cancer associated with excess body weight, possibly strongest during early adulthood.

*

Corresponding Author: Ghislaine Scélo, International Agency for Research on Cancer, Genetic Epidemiology Group, 150 Cours Albert Thomas, 69008 Lyon FRANCE, Tel: +33 (0) 472738173, Fax: +33 (0) 472738342, [email protected].

Urayama et al.

Page 2

Keywords

NIH-PA Author Manuscript

body mass index; body size; pancreatic cancer; risk factor; weight gain

INTRODUCTION More than 250,000 pancreatic cancer cases are registered worldwide each year with some of the highest rates observed in areas of central Europe including Poland, Czech Republic, and Slovakia.1, 2 Disease survival is among the poorest of all neoplasms exhibiting a median of less than six months and case-fatality reaching close to 90% within twelve months of diagnosis.3, 4 Relatively little is known about the causes of pancreatic cancer with the exception of advanced age, smoking, family history of pancreatic cancer, and history of diabetes mellitus and chronic pancreatitis.5

NIH-PA Author Manuscript

Over the past decade, evidence has accumulated supporting a role for excess body weight in the etiology of pancreatic cancer. The biological plausibility of this association stems from the strong relationships observed between obesity and abnormal glucose metabolism and hyperinsulinemia6, 7 which are known to have the capacity to increase local blood flow and promote cell proliferation within the pancreas.8, 9 Epidemiologic studies examining the health effects of excess body weight have largely focused on the use of the body mass index (BMI). A recent meta-analysis conducted among 21 prospective cohort studies showed a statistically significant elevated risk of pancreatic cancer associated with each 5 kg/m2 increase in BMI in both males and females.10 While these findings offer substantial support for a causal relationship, previous studies have been largely inconsistent regarding differential effects by sex and other major risk factors,11–14 and more evidence is beginning to emerge suggesting that onset of overweight or obesity earlier in life may have a larger impact on pancreatic cancer risk.15, 16 Moreover, further clarity and confirmation may be achieved through the evaluation of alternative measures of excess body weight. As a measure based only on height and weight, BMI makes simplistic assumptions about the distribution of muscle and bone mass, thus, it may not reflect an accurate measure of body fat for certain individuals, namely, athletes and the elderly.17, 18 Consistent results among multiple indicators of excess body weight in pancreatic cancer studies may strengthen the evidence in support of this association.

NIH-PA Author Manuscript

In this current analysis conducted among a large central European sample of pancreatic cancer cases and controls, we examined the association between excess body weight and pancreatic cancer risk using two different measures, BMI and pictogram body size score, obtained for multiple time periods.

MATERIALS AND METHODS Study population The study had a case-control design and was conducted in five areas of Czech Republic (Prague, Olomouc, Ostrava, Ceske Budejovice, and Brno) and five areas of Slovakia (Banska Bystrica, Bratislava, Martin, Zilina, and Trencin). In each area, a series of newly diagnosed cases of primary pancreatic cancer was recruited between October 2004 and June 2009 in the Czech Republic and between October 2007 and July 2009 in Slovakia, together with a set of controls that were frequency-matched to cases on age and sex. Cases were recruited in hospitals that treated essentially all pancreatic cancers in each area. The patient was asked to participate if he/she presented at the hospital with clinical or imaging suspicion of pancreatic cancer and had lived in the study area for at least one year. This ultra rapid

Int J Cancer. Author manuscript; available in PMC 2012 December 15.

Urayama et al.

Page 3

NIH-PA Author Manuscript

case ascertainment method included contact with the patients prior to confirmation of the diagnosis. Identification of cases occurred through an active search of clinical and pathological departments. In total, 750 patients were approached for inclusion in the study, of whom 652 were diagnosed with pancreatic cancer (excludes known pancreatic endocrine tumors, i.e. islets cell carcinomas); 6 (0.9%) cases died before the interview (next-of-kin interviews were not used), 53 (8.1%) refused to participate, and 11 (1.7%) were too ill to be interviewed. Another 5 cases were excluded from the study because of missing information for height or weight, and body size score at ages 20 and 40, 2 cases who were underweight (BMI24.5)

154 173

Q3 (24.9–27.3)

Q4 (>27.3)

Int J Cancer. Author manuscript; available in PMC 2012 December 15. 153 130

Q3 (27.2–30.4)

Q4 (>30.4)

117 61

Medium

High

unit increase

357

Low

At age 20 years

Body Size Score a, d

per 5

151

Q2 (24.4–27.1)

kg/m2

131

Q1 (18.5–24.3)

2 years prior to interview

per 5

114

Q2 (23.1–24.8)

kg/m2

106

Q1 (18.5–23.0)

At age 40 years e

per 5

113

kg/m2

101

Q2 (21.2–22.8)

N

11.4

21.9

66.7

23.0

27.1

26.7

23.2

31.6

28.2

20.8

19.4

30.4

29.9

21.0

18.7

%

Cases

Q1 (18.5–21.1)

At age 20 years

BMI (kg/m2) a

Excess body weight measure

50

107

415

148

147

147

147

143

141

141

141

144

145

142

142

N

8.7

18.7

72.6

25.1

25.0

25.0

25.0

25.3

24.9

24.9

24.9

25.1

25.3

24.8

24.8

%

Controls

1.17

1.64

1.39

1.00

1.00

0.94

1.11

1.13

1.00

1.29

1.65

1.43

1.07

1.00

1.43

1.70

1.67

1.15

1.00

OR

1.06

1.08

1.02

Ref

0.88

0.67

0.79

0.81

Ref

1.10

1.17

1.01

0.74

Ref

1.14

1.19

1.17

0.80

Ref

1.29

2.48

1.90

1.14

1.31

1.55

1.57

1.53

2.34

2.04

1.53

1.80

2.44

2.38

1.66

95% CI

Model 1 b

1.15

1.66

1.38

1.00

0.98

0.91

1.04

1.07

1.00

1.24

1.57

1.40

1.04

1.00

1.45

1.79

1.81

1.15

1.00

OR

1.04

1.08

0.99

Ref

0.85

0.63

0.73

0.75

Ref

1.04

1.09

0.97

0.72

Ref

1.15

1.23

1.24

0.79

Ref

1.28

2.57

1.91

1.13

1.30

1.47

1.52

1.47

2.27

2.03

1.52

1.84

2.61

2.63

1.69

95% CI

Model 2 c

Association between body mass index and body size score at ages 20 and 40 years and 2 years prior to interview and risk of pancreatic cancer, 2004– 2009.

NIH-PA Author Manuscript

Table 2 Urayama et al. Page 15

NIH-PA Author Manuscript 178 171

Medium

High

141 247

Medium

High

44.3

25.3

30.5

31.6

32.9

35.5

%

259

152

173

166

156

243

N

44.4

26.0

29.6

29.4

27.6

43.0

%

0.98

0.93

0.93

1.00

1.12

1.37

1.50

1.00

OR

0.91

0.70

0.68

Ref

1.03

1.01

1.12

Ref

1.06

1.24

1.28

1.23

1.85

2.01

95% CI

Model 1 b

0.96

0.85

0.92

1.00

1.08

1.23

1.36

1.00

OR

0.88

0.63

0.66

Ref

0.98

0.90

1.00

Ref

1.04

1.15

1.28

1.19

1.69

1.86

95% CI

Model 2 c

e Excludes subjects less than age 40 years.

Pictogram body size scores 1–3 categorized as "Low", 4 as "Medium", and 5–9 as “High".

d

c OR and 95% CI estimated using logistic regression including center, age at interview (continuous), sex, diabetes mellitus, chronic pancreatitis, smoking (past versus never, current versus never), and alcohol (past versus never, current versus never). There was incomplete covariate data for 7 cases and 3 controls.

OR and 95% CI estimated using logistic regression including center, age at interview (continuous), and sex.

b

Analysis excludes underweight subjects (BMI24.5)

81 42

Medium

High

Int J Cancer. Author manuscript; available in PMC 2012 December 15. 93 113

Q3 (24.9–27.3)

Q4 (>27.3)

111 113

Medium

High

per unit increase

78

Low

Body size score c

per 5

63

Q2 (23.1–24.8)

kg/m2

36

Q1 (18.5–23.0)

BMI (kg/m2)

At Age 40 Years a

per unit increase

190

Low

Body size score c

per 5 kg/m2

61 107

Q2 (21.2–22.8)

28

N

Q1 (18.5–21.1)

BMI (kg/m2)

At Age 20 Years a

Excess body weight measure

37.4

36.8

25.8

37.1

30.5

20.7

11.8

13.4

25.9

60.7

37.8

34.0

19.4

8.9

%

Cases

112

97

98

92

89

75

51

39

68

216

91

96

83

53

N

36.5

31.6

31.9

30.0

29.0

24.4

16.6

12.1

21.1

66.9

28.2

29.7

25.7

16.4

%

Controls

Males

1.04

1.12

1.32

1.00

1.35

1.83

1.62

1.26

1.00

1.15

1.29

1.39

1.00

1.83

3.01

2.48

1.48

1.00

OR b

0.91

0.73

0.85

Ref

1.04

1.05

0.92

0.70

Ref

1.00

0.76

0.92

Ref

1.29

1.67

1.38

0.79

Ref

1.18

1.74

2.04

1.76

3.20

2.86

2.28

1.33

2.19

2.12

2.60

5.41

4.46

2.74

95% CI

58

67

114

60

61

51

70

19

36

167

45

54

52

73

N

24.3

28.0

47.7

24.8

25.2

21.1

28.9

8.6

16.2

75.2

20.1

24.1

23.2

32.6

%

Cases

54

59

145

51

52

66

90

11

39

199

53

49

59

89

N

20.9

22.9

56.2

19.7

20.1

25.5

34.8

4.4

15.7

79.9

21.2

19.6

23.6

35.6

%

Controls

1.13

1.27

1.36

1.00

1.09

1.26

1.25

0.90

1.00

1.14

2.65

1.24

1.00

1.17

1.06

1.64

1.13

1.00

OR b

Females

0.97

0.79

0.86

Ref

0.85

0.74

0.74

0.54

Ref

0.97

1.16

0.72

Ref

0.84

0.62

0.96

0.67

Ref

1.31

2.06

2.16

1.40

2.13

2.11

1.51

1.35

6.03

2.12

1.64

1.81

2.80

1.89

95% CI

0.887

0.827

0.259

0.038

P value (interaction)

Body mass index and body size at ages 20 and 40 years and risk of pancreatic cancer stratified by sex, 2004–2009.

NIH-PA Author Manuscript

Table 3 Urayama et al. Page 17

NIH-PA Author Manuscript

NIH-PA Author Manuscript

Analysis excludes underweight subjects (BMI