Elsevier

Annals of Epidemiology

Volume 16, Issue 3, March 2006, Pages 206-212
Annals of Epidemiology

Folate Levels and Cancer Morbidity and Mortality: Prospective Cohort Study from Busselton, Western Australia

https://doi.org/10.1016/j.annepidem.2005.03.010Get rights and content

Purpose

To test a community population for the hypothesis that carcinogenesis is related to blood folate levels.

Methods

Prospective analysis of cancer mortality data for a cohort of 964 men (person-time follow up: 20,254 years) and 1024 women (person-time follow up: 24,970 years) and morbidity data for a subcohort, all of whom participated in the 1969 Busselton (Western Australia) Health survey. Outcome measures were adjusted hazard ratios according to baseline folate levels for total cancer mortality and morbidity and site specific mortality and morbidity for colorectal, lung, breast, and prostate cancers.

Results

In total, there were 278 cancer deaths—45 from colorectal cancer, 44 from lung cancer, 15 from breast cancer, and 31 from prostate cancer. Decreased serum folate levels showed an independent association with increased prostate cancer mortality risk, the adjusted hazard ratio per decrease of 2 μg/L was 1.56 (CI: 1.05, 2.38), men whose levels were in the lowest quartile had an adjusted hazard ratio of 4.79 (CI: 1.56, 14.43) for subsequent death from prostate cancer. The morbidity subcohort data showed that decreased red blood-cell folate was significantly associated with increased events due to breast cancer, the adjusted hazard ratio per decrease of 100 μg/L was 1.96 (CI: 1.22, 3.12), women in the lowest quartile of red cell folate levels had an adjusted hazard ratio of 6.46 (CI: 1.19, 35.07) for a subsequent breast cancer event. Mortality and morbidity from colorectal or lung cancers were not associated with folate levels.

Conclusions

Independent associations, assessed over periods greater than 20 years, were demonstrated between decreased folate levels and increased risks of prostate cancer mortality and breast cancer morbidity.

Introduction

Deficiency of folate, a water soluble B vitamin, has been associated with anemia, neural tube defects, cardiovascular disease, and, more recently, carcinogenesis (1). Investigating folate metabolism in several types of cancer is currently an important area of research 1, 2. The most compelling clinical and epidemiological evidence linking lower folate levels, including levels not necessarily previously classed as deficient, with increased cancer risk has been reported for colorectal cancer 3, 4. Epidemiological studies have also reported links for which the evidence is currently less strong, between dietary folate intake and breast, lung, cervical, esophageal, gastric, and pancreatic cancers (1).

The purpose of this prospective cohort study was to test the hypothesis that a reduced incidence of cancer mortality or morbidity was associated with higher initial levels of serum and red cell folate in a community population. Two analyses were conducted; the first tested the cohort for an independent association between baseline folate levels and cancer mortality over a 29-year follow-up period; the second tested a subcohort of the same population for cancer morbidity over a 23 year follow-up period.

Section snippets

Subjects

Busselton is a seaside town of Western Australia, and the population is predominantly of Caucasian origin. Cross-sectional mass health surveys of adults listed on the electoral roll (enrolment to vote is compulsory in Australia) were undertaken at intervals of 3 years from 1966 to 1981. The study was approved by the Human Research Ethics Committee, University of Western Australia.

The conduct of the surveys, including a detailed description of the study population, subject examination, and

Cancer Mortality Cohort

Table 1 displays the 1969 baseline risk characteristics according to serum folate quartile groups, and Table 2 displays the risk characteristics according to red-cell folate quartile groups for the mortality cohort, which comprised 964 men and 1024 women, with survival of at least 3 years from baseline. Their average age was about 57 years, and the risk factor characteristics are typical of population samples surveyed around that time. Serum folate and red cell folate levels showed a moderate

Discussion

This prospective cancer mortality analysis presents a unique opportunity to examine potential associations of folate levels obtained at baseline and cancer mortality over an extended 29-year follow-up period. The possibility of reverse causality arising from participants who already had cancer at presentation to the 1969 Busselton Health survey was limited by excluding those who died within the first 3 years of the survey. Lower serum folate concentrations were independently associated with an

References (18)

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