Genetic Variation and Cancer

Nutrigenomics and Personalized Nutrition

2022
Anticancer Research September 2017, 37 (9) 4759-4766
Cancer and Adenoma
• Cancer: A term for diseases in which abnormal cells divide without
control and can invade nearby tissues.
• Adenoma: A tumor that is not cancer. It starts in gland-like cells of the
epithelial tissue (thin layer of tissue that covers organs, glands, and
other structures within the body).
• The basic difference between a benign tumor and a cancer is its
slower growth and lower capacity to spread. In other words
adenomas are much less aggressive in terms of growth than
adenocarcinomas.
Research on genetic variation in metabolism
of dietary factors in relation to cancer
• The goal: allows more precise public health advice about dietary intake,
use of supplements, and genetic testing to be given, in turn prevention of
cancer.
• Few definite relationships between diet and cancer risk have been
established. It is hard to provide clear, understandable, precise dietary
advice for population.
• The extent of change in diet that has been achieved by population-based
interventions has in general not been substantial >> only for subgroup
“genetic.”
• Behavioral interventions may not be inadequate to produce preventive
effects in groups; other approach might be needed.
• Limitations of studying main effects of dietary factors only and
potential for advances offered by investigating gene-disease relations
• Difficult to develop clear guidance about the role of diet in cancer
prevention on the basis of observational data
• e.g. β-carotene supplement might prevent lung cancer, not clear in
other organs protective effects of fruit & vegetables was suggested,
but not clear
Journal of the National Cancer Institute, Vol. 96, No. 21
Konsumsi legumes (polong-polongan) meningkatkan risiko
penyakit kardiovaskuler secara signifikan.

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British Journal of Cancer (2011) 104(1), 6 – 11
• Therefore, the investigation of the effects of genetic variations in the
host that are thought to influence metabolism of nutrients and food
groups in cancer risk is important!

e.g. Polymorphisms influencing

1) folate metabolism
2) heterocyclic amines by cooking meats
3) insulin status
4) alcohol
Polymorphisms influencing folate metabolism
• A major sources of folate : vegetables, particularly green leafy
vegetables
• Folate deficiency causes NTD, but mainly associated with MTHFR
SNPs
• Molecular and cellular roles of folate: involved in DNA synthesis, DNA
methylation, and DNA repair

NOTES: The MTHFR gene provides instructions for your body to

make the MTHFR protein, which helps your body process folate.
Your body needs folate to make DNA and modify proteins.
Neural Tube Defects and Spina Bifida
Folate fortification in cereal and grains
 FIGURE 2. Neural tube defect rates per 10,000 population, by
race/ethnicity and fortification period status --- National Birth
Defects Prevention Network,* 1995--2007
CDC Grand Rounds: Additional Opportunities to Prevent Neural Tube Defects with Folic Acid Fortification
Other polymorphisms in folate metabolism: variants in
MTR (methionine synthase)
MTRR (methionine synthase reductase)
CBS (cystathionine beta-synthase)
TS (thymidylate synthase)
mostly studied in colorectal cancer but also some in esophagus and
hematopoietic malignancy
Folate metabolism

Nature Reviews Cancer 3, 601-614 (August 2003)

Decreased dietary folate intake and colon
carcinogenesis

Nature Reviews Cancer 3, 601-614 (August 2003)

Rest, then read
e.g. C677T and A1298C in MTHFR

Martin DN et al, BMC Cancer 2006, 6:257

Variasi gen A1298C memiliki efek pada risiko
penyakit kanker payudara pada ras:

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Exp. Mol. Med. Vol. 36(2), 116-121, 2004
J Hum Genet (2007) 52:73–85 DOI 10.1007/s10038-006-0082-5
Seseorang dengan alela T pada variasi gen C677T memiliki risiko
kanker payudara yang lebih rendah, tetapi tidak signifikan.

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Your assignment
• Mulai sekarang carilah 1 artikel penelitian nutrigenetic dan
nutrigenomic yang berkaitan dengan penyakit tidak menular dan/atau
diet
• Pelajarilah hasil dari penelitian tersebut dan presentasikan di kelas.
• Kumpulkan judul dan tautan artikel/jurnal di:
https://docs.google.com/spreadsheets/d/1PNURwVg3pU6eafeCoYQn
jyuNvnneiRD1GYLUTxclU_Q/edit?usp=sharing