Association of cholesterol with risk of pancreatic cancer: A meta-analysis

Table 1 Characteristics of studies for dietary cholesterol included in the meta-analysis

Ref.	Country (year)	Study design	Mean age (case/control)Percentage of males (case/control)	Sample size (cases)	Cut-points for cholesterol exposure RR (95%CI)	Adjustment for covariates
Lin et al[13]	Japan	Case-control	64.7/65.1	327	Dietary cholesterol exposure (mg), < 206 (referent), 206-330,	Age and pack-years of smoking
	-2005		NA	-109	> 330 [2.06 (1.11-3.85)]
Chan et al[14]	United States	Case-control	NA	2233	Dietary cholesterol exposure (g/d) median, 122.8 (referent), 192.6, 257.6, 368.9 [1.5 (1.1-2.0)]	Age, sex, BMI, race, education, smoking, history of diabetes and energy intake
	-2007		54.7/51.9	-532
Hu J et al[15]	Canada	Case-control	61.6/57.1	5667	Dietary cholesterol cut-point	Age, sex, BMI, province, education, alcohol drinking, pack year smoking, total of vegetable and fruit intake, saturated fat and total energy intake
	-2012		56.2/50.5	-628	(mg/wk) < 966.261 (referent), 966.262-1412.753, 1412.754-1880.265,
					> 1880.266 [1.57 (1.09-2.26)]
Howe et al[17]	Metropolitan Toronto	Case-control	64.6/64.8	754	Mean difference per day	Caloric and fibre intake, lifetime cigarette consumption
	-1990		56.6/53.5	-249	quartile 4-quartile 1 (569 mg) [0.95 (0.51-1.75)]
Bueno de Mesquita et al[18]	Netherlands	Case-control	NA	644	Dietary cholesterol	Age, sex, response status, total smoking and dietary intake of energy
	-1991		54.9/48.3	-164	[1.33 (0.72-2.45)]
Lucenteforte et al[19]	Italy	Case-control	NA	978	First quintile of cholesterol exposure (referent), second vs first,	Year of interview, education, tobacco smoking, history of diabetes and total energy intake
	-2010		53.4/53.4	-326	third vs first, fourth vs first,
					fifth vs first [1.10 (0.68-1.77)]
Baghurst et al[26]	Australia	Case-control	NA	357	First quintile of cholesterol exposure (referent), second vs first, third vs first, fourth vs first [3.19 (1.58-6.47)]	Age and pack-years of smoking
	-1991		50.0/56.1	-104
Ghadirian et al[27]	Canada	Case-control	63.9/62.1	418	First quintile of cholesterol exposure (referent), second vs first, third vs first, fourth vs first [2.24 (0.83-6.05)]	Age, sex, lifetime cigarette consumption, response status and total energy intake
	-1995		54.2/51.5	-179
Heinen et al[28]	The Netherlands	Case-cohort	NA	120852	Dietary cholesterol (mg/d), first quintile of cholesterol exposure (referent), second vs first, third vs first, fourth vs first, fifth vs first [0.78 (0.52-1.18)]	Age, sex, BMI, energy, smoking, alcohol, history of diabetes mellitus, history of hypertension, vegetables and fruits intake
	-2009		52.9/49.1	-350
Kalapothaki et al[29]	Greece	Case-control	NA	362	Dietary cholesterol (mg), an increment of about one standard deviation of the energy-adjusted residual of the corresponding nutritional variable [1.19 (0.96-1.47)]	Age, sex, hospital, past residence, years of schooling, smoking, diabetes mellitus and energy intake
	-1993		NA	-181
Michaud et al[30]	United States	Cohort	NA	88802	Median of cholesterol exposure (g/d) 212 (referent), 275, 322, 371, 466 [1.11 (0.67-1.83)]	Pack-years of smoking, BMI, history of diabetes mellitus, caloric intake, height, physical activity, menopausal status and glycemic load intake
	-2003		NA	-178
Nöthlings et al[31]	Hawaii and Los Angeles	Cohort	65/60	190545	Cholesterol density (mg/1000 kcal per day) median intake 56.8 (referent), 81.6, 100.4, 120.8, 156.8 [1.09 (0.89-1.32)]	Age, ethnicity, history of diabetes mellitus, familial history of pancreatic cancer, smoking status and energy intake
	-2005		51.2/45.3	-482
Stolzenberg-Solomon et al[32]	Finland	Cohort	58/57	27111	First quintile of cholesterol exposure (referent), second vs first,	Energy intake, age, years of smoking and energy-adjusted saturated fat intake
	-2002		NA	-163	third vs first, fourth vs first,
					fifth vs first [0.92 (0.53-1.59)]
Zatonski et al[33]	Poland	Case-control	62.2/63.2	305	First quintile of cholesterol exposure (referent), second vs first, third vs first, fourth vs first [4.31 (1.60-11.59)]	Cigarette lifetime consumption and calories
	-1991		61.8/45.6	-110

NA: Not available; BMI: Body mass index.

Table 2 Characteristics of studies for serum total cholesterol included in the meta-analysis

Ref.	Country (year)	Study design	Mean age (case/control) Percentage of males (case/control)	Sample size (cases)	Cut-points for cholesterol Exposure RR (95%CI)	Adjustment for covariates
Wu et al[16]	China (2012)	Case-control	59.3/59.358.6/58.6	840(210)	Serum TC < 5.70 mmol/L (referent),≥ 5.70 mmol/L [1.793 (1.067-3.013)]	Age, sex, hypertension, HBV markers, the levels of HDL, LDL, Tri and Apo B
Stolzenberg-Solomon et al[20]	Finland (2002)	Cohort	NA	29048(172)	Serum TC < 5.18 mmol/L (referent),≥ 5.18 mmol/L [0.88 (0.60-1.28)]	Age, years smoked, cigarettes smoked per day, self-reported history of diabetes andbronchial asthma, occupational activity and measured high blood pressure
Johansen et al[21]	Austria, Norway, and Sweden (2010)	Cohort	NA	289866(543)	Serum TC mean level (mmol/L) 4.5 (referent), 5.3, 5.8, 6.4, 7.6 [0.70 (0.53-0.93)]	Age, BMI and smoking status
Johansen et al[21]	Austria, Norway, and Sweden (2010)	Cohort	NA	288834(314)	Serum TC mean level (mmol/L) 4.4 (referent), 5.1, 5.7, 6.3, 1.11 [0.75 (0.53-1.64)]	Age, BMI and smoking status
Kitahara et al[34]	South Korea (2011)	Cohort	NA	756604(1799)	Serum TC (mg/dL) < 160 (referent), 160-179, 180-199, 200-239, ≥ 240 [0.88 (0.74-1.05)]	Smoking, drinking, fasting serum glucose,BMI, hypertension and physical activity
Kitahara et al[34]	South Korea (2011)	Cohort	NA	433115(776)	Serum TC (mg/dL) < 160 (referent), 160-179, 180-199, 200-239, ≥ 240 [0.96 (0.74-1.24)]	Smoking, drinking, fasting serum glucose,BMI, hypertension and physical activity
Kuzmickiene et al[35]	Lithuania (2013)	Cohort	NA	6788(73)	Serum TC (mmol/L) < 5.20 (referent), 5.20-5.89, 5.90-6.62, ≥ 6.63 [1.76 (0.87-3.55)]	Age, BMI, smoking status, alcohol consumption and education
Xu et al[36]	China (2011)	Case-control	61.4/60.7459.3/60.5	602(290)	Serum TC (mmol/L) < 5.72 (referent), ≥ 5.72 [1.01 (0.88-1.17)]	Diabetes mellitus, smoking, hypertension, family history of cancer, history of gastrointestinal surgery, history of biliary disease, history of chronic pancreatitis and triglyceride

NA: Not available; BMI: Body mass index.

Table 3 Pooled relative risks of associations between pancreatic cancer and dietary cholesterol and serum total cholesterol

Cholesterol source	Subgroup	No. of studies	Pooled RR (95%CI) REM	I2	Pheterogeneity
Dietary cholesterol	All studies	14	1.308 (1.097-1.559)	55.3%	0.006
	After excluding two studies[24,31] (RR > 3.0)	12	1.204 (1.050-1.380)	29.4%	0.158
	Study design
	Case-control	10	1.523 (1.226-1.893)	49.7%	0.037
	Cohort	4	1.023 (0.871-1.200)	0.0%	0.508
	Continent
	North America	6	1.275 (1.058-1.537)	29.3%	0.215
	Europe	6	1.149 (0.863-1.531)	55.4%	0.047
	Others	2	2.495 (1.565-3.977)	0.0%	0.362
Serum TC	All studies	8	1.003 (0.859-1.171)	55.5%	0.028
	Continent
	Europe	4	1.034 (0.722-1.481)	65.1%	0.035
	Asia	4	1.005 (0.847-1.192)	56.2%	0.077

TC: Total cholesterol; REM: Random effect model.