Purpose

Vitamin D has been implicated in lowering lung cancer risk, but serological data on the association among never-smoking women are limited. We report results examining the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with lung cancer risk among female never smokers. We also examined whether the association was modified by vitamin D supplementation and serum vitamin A concentrations.

Methods

In the Women's Health Initiative, including the calcium/vitamin D (CaD) Trial, we selected 298 incident cases [191 non-small cell lung cancer (NSCLC) including 170 adenocarcinoma] and 298 matched controls of never smokers. Baseline serum 25(OH)D was assayed by a chemiluminescent method. Logistic regression was used to estimate odds ratios (ORs) for quartiles and predefined clinical cutoffs of serum 25(OH)D concentrations.

Results

Comparing quartiles 4 versus 1 of serum 25(OH)D concentrations, ORs were 1.06 [95% confidence interval (CI) 0.61-1.84] for all lung cancer, 0.94 (95% CI 0.52-1.69) for NSCLC, and 0.91 (95% CI 0.49-1.68) for adenocarcinoma. Comparing serum 25(OH)D ≥ 75 (high) versus <30 nmol/L (deficient), ORs were 0.76 (95% CI 0.31-1.84) for all lung cancer, 0.71 (95% CI 0.27-1.86) for NSCLC, and 0.81 (95% CI 0.31-2.14) for adenocarcinoma. There is suggestive evidence that CaD supplementation (1 g calcium + 400 IU D₃/day) and a high level of circulating vitamin A may modify the associations of 25(OH)D with lung cancer overall and subtypes (p interaction <0.10).

Conclusions

In this group of never-smoking postmenopausal women, the results did not support the hypothesis of an association between serum 25(OH)D and lung cancer risk.

Background

Dietary energy density (DED) is the ratio of energy (kilocalories or kilojoules) intake to food weight (grams) and is a measure of diet quality. Consumption of foods high in DED has been associated with weight gain in adults.

Objective

To investigate the association between baseline DED and incident obesity-associated cancers in the Women's Health Initiative.

Design

Prospective cohort study of clinical trial and observational study participants.

Participants/setting

Postmenopausal women aged 50 to 79 years (N=92,295) enrolled in the observational study or the calcium and vitamin D trial and hormone replacement therapy trials of the Women's Health Initiative.

Main outcome measures

Incident, medical record-adjudicated, obesity-related cancers during follow-up. Exposure variable was DED (kilocalories per gram for the total diet) from self-reported dietary intake at baseline using a food frequency questionnaire.

Statistical analyses

The associations between DED and each incident cancer, or any obesity-related cancer, were examined using competing-risks regression models, with death as a competing risk. Body mass index-stratified models were generated to investigate body mass index as a potential modifying factor.

Results

DED was associated with higher body mass index (28.9±6.0 vs 26.3±4.9) and waist circumference (89.3±14.2 vs 82.4±12.4 cm) for DED quintiles 5 vs 1, respectively. DED was associated with a 10% increased risk of any obesity-related cancer (subhazard ratio_{Q5 vs Q1}: 1.1, 95% CI 1.03 to 1.2; P=0.004). This increased risk appeared limited to women who were normal weight at enrollment.

Conclusions

Higher DED may be a contributing factor for obesity-related cancers, especially among normal-weight postmenopausal women and, as such, could serve as a modifiable behavior for dietary interventions to reduce obesity-associated cancer risk.