Folate Levels and Cancer Morbidity and Mortality: Prospective Cohort Study from Busselton, Western Australia
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)
Folate and carcinogenesis:Evidence, mechanisms and implications
J Nutr Biochem
(1999)Role of folate in colon cancer development and progression
J Nutr
(2003)- et al.
Age and secular trends in risk factors for cardiovascular disease in Busselton
Aust J Public Health
(1995) - et al.
Reduced breast cancer risk with increasing serum folate in a casecontrol study of the C677T genotype of the methylenetetrahydrofolate reductase gene
Eur J Cancer
(2004) - et al.
Folate status: Effects on pathways of colorectal carcinogenesis
J Nutr
(2002) - et al.
Folate and the risk of colorectal, breast and cervix cancer: The epidemiological evidence
Swiss Med Wkly
(2001) - et al.
Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum
Am J Med Genet
(2001) Mass health examinations in the Busselton population, 1966 to 1970
Med J Aust
(1972)- et al.
Automation of the assay of folate in serum and whole blood
J Clin Path
(1970)
Cited by (73)
Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival
2020, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Our findings are consistent with a metanalysis study of 2 Norwegian randomized controlled clinical trials which found that CaP was the only cancer type where increased risk of cancer was shown for folic acid supplements [12]. Although several studies did not identify [13–15] or revealed an inverse [16,17] associations with CaP incidence and mortality, research has not defined the optimal level of folate in the general population. The results of our study lead us to proceed with planning a folate reduction diet particularly in men initiating androgen deprivation therapy.
Divergence between dietary folate intake and concentrations in the serum and red blood cells of aging males in the United States
2016, Clinical NutritionCitation Excerpt :The global effect of higher serum and RBC folate concentrations despite equivalent amounts of total daily DFE intake in men of different ages is unknown. There have been many studies examining the risks and benefits of folate supplementation, especially as it relates to cancer [7,14,18–20]. However, most of these studies have assumed that ingestion of a certain quantity of folate or folic acid will produce equivalent serum folate concentrations, and thus equal clinical affects.
Opposing roles of folate in prostate cancer
2013, UrologyCitation Excerpt :A third category of variation between these studies is the definition of the intervention variable, with some groups estimating folate and folic acid intake from dietary questionnaires, and others using quantified serum folate levels. Six studies measured serum folate levels,22,26,28-30,34 whereas 6 others reported various levels of folate or folic acid intake.24,25,27,31,32,35 Only 1 study reported both variables.33
Scientific opinion on the tolerable upper intake level for folate
2023, EFSA Journal