Iron, zinc and calcium in lung cancer

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Hi All,

It seemed to be surprising that calcium intake was such a large risk factor for

lung

cancer in the below pdf-available paper. The benefit of zinc and risk of iron

intake appear to be more reasonable. Prospective study is good.

Zhou W, Park S, Liu G, DP, Wang LI, Pothier L, Wain JC, Lynch TJ,

Giovannucci

E, Christiani DC.

Dietary iron, zinc, and calcium and the risk of lung cancer.

Epidemiology. 2005 Nov;16(6):772-9.

PMID: 16222167

BACKGROUND: Iron, zinc, and calcium are all involved in the metabolism of

reactive

oxygen species and may compete with each other for similar binding sites.

Dietary

intakes of these micronutrients have been associated with altered risks of

colorectal, breast, and prostate cancers. METHODS: In this Massachusetts

hospital-based case-control study of 923 patients with lung cancer and 1125

healthy

controls, we studied the associations between dietary iron, zinc, and calcium

intake

and the risk of lung cancer. Dietary intake was assessed at the time of

recruitment

(1992 to 2000) with the use of a 126-item semiquantitative food-frequency

questionnaire. We analyzed the data using multiple logistic regression models

adjusting for smoking history and other potential risk factors. RESULTS: The

adjusted odds ratios of dietary iron, zinc, and calcium from food sources were

1.45

(95% confidence interval=1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29),

respectively, for the highest quintile versus the lowest quintile of each

micronutrient. Stronger associations between micronutrients and lung cancer risk

were found when iron, zinc, and calcium were included together in the same

model.

The associations between dietary micronutrients intake and lung cancer risk were

stronger among current smokers than among former smokers. When we examined

intake

from supplements as well as diet, associations were similar to those for diet

alone.

CONCLUSIONS: Dietary iron, zinc, and calcium may play an important role in the

development of lung cancer, especially among current smokers. These results need

to

be confirmed in large prospective studies.

TABLE 2. Associations of Intake of Dietary Iron, Zinc and Calcium With Lung

Cancer,

After Energy-Residual Adjustment

===================================================

Dietary Quintiles----PTrend

1* 2 3 4 5----

===================================================

Dietary iron (mg/d) </=10.76 10.77–12.17 12.18–13.66 13.67–16.23 =/>16.24

No. cases/controls 192/225 159/225 184/224 173/226 215/225

Age-adjusted OR (95% CI) † 1.00 0.72 (0.54–0.96) 0.83 (0.62–1.10) 0.78

(0.58–1.04) 0.88 (0.66–1.17) 0.88

Multivariable 1 OR (95% CI) †‡ 1.00 0.98 (0.69–1.38) 1.03 (0.73–1.44) 1.10

(0.78–1.57) 1.45 (1.03–2.06) 0.01

Multivariable 2 OR (95% CI) ‡¶ 1.00 1.05 (0.74–1.50) 1.22 (0.85–1.74) 1.37

(0.94–1.99) 1.95 (1.33–2.86) 0.0002

Dietary zinc (mg/d) </=8.87 8.88–10.03 10.04–11.26 11.27–12.87 =/>12.88

No. cases/controls 246/224 190/223 178/227 157/225 152/226

Age-adjusted OR (95% CI) † 1.00 0.81 (0.62–1.07) 0.78 (0.59–1.03) 0.68

(0.51–0.90) 0.63 (0.48–0.84) 0.0008

Multivariable 1 OR (95% CI) †‡ 1.00 0.97 (0.71–1.35) 0.94 (0.67–1.31) 0.81

(0.57–1.14) 0.71 (0.50–0.99) 0.03

Multivariable 2 OR (95% CI) ‡¶ 1.00 0.83 (0.59–1.16) 0.75 (0.53–1.07) 0.63

(0.43–0.91) 0.46 (0.31–0.68) =/>0.0001

Dietary calcium (mg/d) </=586.07 586.08–699.79 699.80–836.02 836.03–1013.99

=/>1014.00

No. cases/controls 185/225 177/225 175/225 165/255 221/225

Age-adjusted OR (95% CI) † 1.00 0.98 (0.73–1.30) 0.95 (0.71–1.27) 0.87

(0.65–1.16) 1.21 (0.92–1.60) 0.17

Multivariable 1 OR (95% CI) †‡ 1.00 1.13 (0.81–1.58) 1.28 (0.91–1.80) 1.12

(0.80–1.58) 1.64 (1.17–2.29) 0.005

Multivariable 2 OR (95% CI) ‡¶ 1.00 1.12 (0.80–1.57) 1.24 (0.87–1.75) 1.14

(0.80–1.63) 1.81 (1.27–2.56) 0.0007

===================================================

*Reference category.

† Dietary iron, zinc, and calcium were analyzed in separate models.

‡ Adjusted for age, sex, smoking status, pack-years of smoking, years since

smoking

cessation, total energy, and education levels.

¶ Dietary iron, zinc, and calcium were analyzed in the same model.

TABLE 3. Joint Association of Dietary Iron and Zinc Intake (mg/d) With the Risk

of

Lung Cancer, After Energy-Residual Adjustment

===================================================

Dietary Zinc Intake (mg/d)

>11.69 9.70–11.69 <9.70

3x [No. Cases/Controls Adjusted* OR (95% CI)]

===================================================

Dietary Iron Intake (mg/d)

=/>11.70 21/46 † 1.00 84/128 1.34 (0.67–2.68) 193/202 1.63 (0.85–3.14)

11.70–14.32 73/142 1.01 (0.50–2.03) 106/131 1.64 (0.82–3.25) 120/100 2.17

(1.08–4.34)

14.32 166/188 1.81 (0.93–3.52) 98/113 2.16 (1.07–4.37) 62/75 2.01

(0.96–4.20)

===================================================

*Adjusted for age, sex, smoking status, pack-years of smoking, years since

smoking

cessation, total energy intake, and education levels.

P for trend joint effects of dietary iron and zinc =/>0.0001.

† Reference category.

TABLE 4. Associations of Dietary Iron, Zinc, and Calcium Intake (mg/d) With Lung

Cancer, After Energy-Residual Adjustment, in Subgroups of Age, Sex, Smoking,

Education, Clinical Stages, and Histologic Cell Types

===================================================

No. Cases/Controls

Iron Zinc Calcium

3x [No. Cases/Controls Adjusted* OR (95% CI)]

===================================================

Age †

=/>55 172/432 3.62 (1.76–7.44) 0.0002 0.36 (0.17–0.76) 0.002 2.41 (1.17–4.97)

0.007

=/>55 751/693 1.53 (0.96–2.45) 0.06 0.56 (0.35–0.91) 0.01 1.60 (1.07–2.41)

0.04

Sex

Female 425/608 1.99 (1.15–3.44) 0.006 0.59 (0.32–1.07) 0.005 1.62 (0.97–2.71)

0.10

Male 498/517 2.19 (1.20–3.97) 0.005 0.36 (0.20–0.64) 0.001 2.11 (1.27–3.50)

0.0007

Smoking status

Former smokers 493/515 1.39 (0.81–2.39) 0.23 0.53 (0.31–0.89) 0.03 1.38

(0.86–2.22) 0.28

Current smokers 380/215 4.03 (1.89–8.57) 0.0001 0.41 (0.19–0.88) 0.007 2.43

(1.29–4.58) 0.003

Education levels

High school or lower 506/470 1.98 (1.14–3.44) 0.005 0.41 (0.23–0.72) 0.003

1.75

(1.07–2.85) 0.008

College or above 417/655 1.93 (1.14–3.34) 0.006 0.46 (0.26–0.81) 0.003 1.79

(1.07–2.99) 0.03

Clinical stages

Early stage 523/1125 2.19 (1.37–3.49) 0.0002 0.52 (0.32–0.84) 0.003 1.87

(1.24–2.83) 0.001

Late stage 372/1125 1.63 (1.00–2.67) 0.06 0.41 (0.25–0.68) 0.0004 1.60

(1.02–2.51) 0.03

Histologic cell types

Adenocarcinoma 472/1125 2.00 (1.28–3.12) 0.002 0.38 (0.24–0.59) =/>0.0001

1.51

(1.01–2.26) 0.04

Squamous cell carcinoma 231/1125 1.74 (0.90–3.38) 0.04 0.42 (0.21–0.84) 0.01

2.00

(1.09–3.67) 0.005

===================================================

*Adjusted for age, sex, smoking status, pack-years of smoking, years since

smoking

cessation, total energy intake, and education levels. The micronutrients of

iron,

zinc, and calcium were analyzed in the same model. Correspondence of the highest

quintile versus lowest quintile of each micronutrient.

† Similar associations were found when using age at 60 or 65 as the cutoff

point.

TABLE 5. Associations of Intake of Total (Dietary and Supplemental) Iron, Zinc,

and

Calcium With Lung Cancer, After Energy-Residual Adjustment

===================================================

Micronutrient Quintiles----PTrend

1* 2 3 4 5----

===================================================

Total iron (mg/d) </=10.95 10.96–12.85 12.86–15.52 15.53–22.73 =/>22.74

No. cases/controls 167/225 166/224 209/226 184/225 197/225

Age-adjusted OR (95% CI) † 1.00 0.93 (0.70–1.25) 1.15 (0.87–1.53) 0.92

(0.69–1.22) 1.08 (0.81–1.44) 0.59

Multivariable 1 OR (95% CI) †‡ 1.00 1.09 (0.76–1.54) 1.37 (0.97–1.93) 1.30

(0.91–1.86) 1.71 (1.21–2.41) 0.002

Multivariable 2 OR (95% CI) ‡¶ 1.00 1.17 (0.82–1.68) 1.54 (1.07–2.22) 1.53

(1.04–2.27) 2.06 (1.31–3.24) 0.003

Total zinc (mg/d) </=9.11 9.12–10.64 10.65–12.41 11.42–20.56 =/>20.57

No. cases/controls 219/226 191/225 174/225 168/224 171/225

Age-adjusted OR (95% CI) † 1.00 0.95 (0.72–1.25) 0.85 (0.64–1.13) 0.84

(0.63–1.11) 0.84 (0.63–1.11) 0.30

Multivariable 1 OR (95% CI) †‡ 1.00 1.05 (0.76–1.46) 0.98 (0.69–1.37) 0.84

(0.60–1.20) 1.21 (0.87–1.69) 0.21

Multivariable 2 OR (95% CI) ‡¶ 1.00 0.94 (0.67–1.32) 0.79 (0.55–1.14) 0.63

(0.43–0.92) 0.67 (0.43–1.06) 0.11

Total calcium (mg/d) </=629.93 629.94–768.99 769.00–942.99 943.00–1271.79

=/>1271.80

No. cases/controls 186/225 190/225 159/225 214/255 174/225

Age-adjusted OR (95% CI) † 1.00 0.99 (0.74–1.31) 0.86 (0.64–1.15) 1.10

(0.83–1.45) 0.92 (0.69–1.23) 0.74

Multivariable 1 OR (95% CI) †‡ 1.00 1.10 (0.79–1.53) 1.24 (0.88–1.74) 1.34

(0.96–1.87) 1.48 (1.05–2.08) 0.02

Multivariable 2 OR (95% CI) ‡¶ 1.00 1.04 (0.74–1.46) 1.17 (0.82–1.66) 1.28

(0.91–1.81) 1.45 (1.01–2.08) 0.05

===================================================

*Reference category.

† Total iron, zinc, and calcium were analyzed in separate models.

‡ Adjusted for age, sex, smoking status, pack-years of smoking, years since

smoking

cessation, total energy, and education levels.

¶ Total iron, zinc, and calcium were analyzed in the same model.

Al Pater, PhD; email: old542000@...

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