Evidence indicates the role of dietary composition in driving systemic environmental changes, or epigenetics, which sustain cancer cell progression.
Methionine is an amino acid found in meat, nuts, eggs, and grains that is important for metabolic health, but overconsumption can stimulate changes in DNA methylation, leading to cancer cell proliferation.
However, in vivo tests demonstrate that lower methionine intake supresses production of mammary cancer cells (metastasis), although there are no human studies on breast cancer survival, say the authors of a new study.
Reporting on their findings, they explain: “Cancer cells proliferate rapidly compared to normal cells and require larger quantities of glucose and amino acids to sustain this proliferation. Therefore, metabolic regulation in cancer tissue should differ from corresponding healthy tissue.
“As demand for amino acids increases following malignant transformation, cells may experience a methionine deficiency that could affect these epigenetic processes.”
Breast cancer is the most common malignancy in women globally, accounting for 24.5% of new cases and 15.5% of cancer deaths in 2020, the authors say.
Although the five-year survival rate is over 90%, the figure drops sharply in cases of advanced stage or metastatic breast cancer, they add.
“Epigenetic processes are now recognised as critical in carcinogenesis and progression across multiple tumour sites, including breast cancer incidence and progression,” they write.
Given the poor prognosis in advanced cases and documented epigenetic influence, they suggest “breast cancer survivors may be motivated to make lifestyle changes, including changes in diet, in order to increase survivorship”.
The research aimed to evaluate the long-term effect of dietary methionine intake on breast cancer survival, before and after diagnosis. Dietary folate acid and vitamin B12 are also analysed to rule out a possible association with methionine synthesis and mortality.
Postmenopausal women aged 50 to 79 years were recruited from 40 clinical centres involved in the Women’s Health Initiative (WHI) and assigned to either the clinical trial (CT) or observational study (OS).
The CT included dietary modification (DM), hormone therapy (HT), and calcium and vitamin D (CaD) trials. The CT and OS components were completed in 2004-2005 but subjects were monitored in the WHI Extension Study for an average 16.1 years.
Subjects completed a self-administered food frequency questionnaire (FFQ) to assess dietary intake and information on demographic characteristics were collected.
Ongoing health status was updated every six months in telephone communications and self-reported breast cancer diagnosis verified by medical records.
The authors note that following breast cancer diagnosis, 42% maintained relatively stable dietary methionine intake, while 28% decreased and 30% increased intake, compared with pre-diagnosis levels. Increased dietary methionine was not, however, linked to survival among breast cancer survivors.
Subjects with increased post-diagnosis methionine had lower pre-diagnosis intake of total energy, folate/folic and vitamin B12, and higher post-diagnosis levels, including total protein, compared to those with relatively stable intake. Moreover, participants were more likely to use HT and increase physical activity post-diagnosis - and were more obese prior to diagnosis.
On the other hand, those who decreased post-diagnosis methionine (from 640 mg/day to 623mg/day) exhibited the opposite results and displayed a significantly lower risk of all-cause and breast cancer mortality.
The authors’ comment: “The findings are biologically plausible. Possible mechanisms of anti-tumour effects of methionine restriction include the pervasive dependence on exogenous methionine in cancer due to a defect in methionine synthesis, and due to contextual factors that shape individual tumours.”
Changes in dietary folate/folic acid or vitamin B12 intake were not associated with all-cause or breast cancer mortality.
Overall, there were 772 deaths in total, including 195 from breast cancer and 577 from other causes.
Published online, November 10, 2022: http://doi.org/10.3390/nu14224747
‘Changes in Dietary Intake of Methionine, Folate/Folic Acid and Vitamin B12 and Survival in Postmenopausal Women with Breast Cancer: A Prospective Cohort Study’
Authors: Yangbo Sun, Jay H. Fowke, Xiaoyu Liang, Khyobeni Mozhui, Saunak Sen, Wei Bao, Buyun Liu, Linda G. Snetselaar, Robert B. Wallace, Aladdin H. Shadyab, Nazmus Saquib, Ting-Yuan David Cheng and Karen C. Johnson