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Principal Investigator
Name
Paolo Boffetta
Degrees
M.D/ M.P.H
Institution
The Department of Medical and Surgical Sciences (DIMEC), the University of Bologna
Position Title
Professor and Associate Director for Population Sciences
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
PLCO-1018
Initial CDAS Request Approval
Aug 22, 2022
Title
Fatty acids intake with emphasis on trans fatty acids and risks of Breast cancer and Colorectal Cancer
Summary
Breast cancer (BC) was the most commonly diagnosed cancer and the leading cause of cancer death among females worldwide in 2020 . A combination of different agents causes these increasing trends, including demographic characteristics, life expectancy, socioeconomic status, the different reproductive factors. changes in lifestyle factors for example obesity, physical inactivity, and diet . Several studies have examined the relationship between diet intake, such as varieties of foods, macro and micro nutrient, and dietary patterns with BC risk.

Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer death, with an estimated 1.8 million new cases and 900,000 deaths in 2020 worldwide. A higher incidence is found in men and in highly industrialized countries . Different factors contribute to colorectal cancer incidence, including demographic characteristics and lifestyle factors such as obesity, physical inactivity, and diet. Fat-rich diets are linked to diseases like obesity, cardiovascular disease, and cancer. The changing lifestyle, including the shift of diet composition towards a “westernized” pattern connoted by higher fat, sugar, and animal-source foods intake, leads to an increasing burden of different disease in countries undergoing rapid socioeconomic improvement.

Several epidemiological studies found that types of fats (FAs) are more strongly influenced by a person's health and disease incidence than total fat intake. Different roles are exerted by different types of dietary fats depending on their source such as, ω-3 polyunsaturated fatty acids (PUFAs) play a role in protecting against adipose tissue inflammation, in contrast to omega-6 (ω-6) PUFAs and some saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs), which promote inflammation. Trans fatty acids (TFAs) are found in uman foods in two forms of industrial trans fatty acids (iTFAs) and ruminant trans fatty acids (rTFAs). In general, they have been generated by chemical processes of hydrogenation through in industrial processes or rumen bacteria. Some epidemiological studies raise the hypothesis of a positive association between chronic diseases, in particular cancer, and iTFA isomers, such as elaidic acid (EA). Nevertheless, there are limited reliable data and the associations between rTFA consumption and cancer, for example, vaccenic acid (VA), conjugated linoleic acid (CLA), and palmitelaidic acid, are inconsistent. Further research is needed to clarify the health effects and the carcinogenic potential of TFAs.

According to a cohort study conducted in 2021, higher intake of elaidic acid, one of the iTFAs, was associated with elevated breast cancer risk. The results of one meta-analysis evaluating rTFA intake and breast cancer risk did not demonstrate any association, but the number of studies included was small [9]. Based on a World Cancer Research Fund (WCRF) report published in 2018, evidence of the association between TFAs and breast cancer is limited and requires further investigation. The purpose of this study is to investigate the association between fatty acids intake in particularly Trans fatty acid and risk of breast cancer.
Aims

The study population will include all PLCO study members (both genders, all ages) who satisfactorily completed the baseline and food frequency questionnaire (FFQ), the additional risk factor questionnaire, and do not meet the exclusion criteria.

We will exclude individuals who: 1) died prior to questionnaire being received (0 person-years of follow-up), 2) had incomplete dietary questionnaire, which would not enable to calculation of trans fatty acid intake, 3)had prevalent breast cancer at baseline 5) had unreliable values of BMI or energy intake.

Objectives
The primary objective of this study is to determine the association between dietary intake of total and different types of fatty acids with breast cancer, focusing on TFA type (rTFAs and iTFAs).

Exposure
Consumption (grams per day) of dietary fatty acids (total fat, total MUFAs, total PUFAs, total saturated fatty acids, total Trans fatty acid, total ruminant and industrial trans fatty acid and other subgroups) was assessed using a FFQ.

Outcomes
1- Incident BC
2- BC subgroups (hormone receptor status, histology type, menopausal status, etc.).
3- Incident colorectal cancer, including information on subsites of colorectal ( colon, proximal colon, distal colon, rectum).

Statistical analysis for Risk of Breast Cancer
Cox Proportional Hazards models will be run for overall risk of BC and dietary fatty acids in particular TFAs (separately for iTFAs and rTFAs) intake. Covariates will include potential confounders and known BC risk factors: gender, age, ethnicity, body mass index, height, smoking status, physical activity, alcohol intake, educational level, occupation status, family history of breast cancer, marital status, menopausal status, use of hormonal treatment for menopause, age at first birth, number of children, and energy intake, hormone receptor status, histology type.

The primary analysis will include women of all ages. Secondary analyses will include: 1) stratification of women by menopausal status, ethnicity, hormone receptor status., 2) analysis in men.

Statistical analysis for Risk of Colorectal Cancer
Cox Proportional Hazards models will be run for overall risk of colorectal cancer and dietary fatty acids in particular TFAs intake. Covariates will include potential confounders and known colorectal cancer risk factors: age, gender, race/ethnicity, family history, height, alcohol intake, educational level, occupation status, marital status, energy intake, body mass index, physical activity, smoking, and dietary variables including vegetable, fruit, fiber, calcium, red meat, processed meat, folate.

The primary analysis will include all cases of colorectal cancer. Secondary analyses will include: 1) risk of colorectal cancer by specific cancer site, 2) different type of fatty acids and trans fatty acids 3) stratification by age, gender, ethnicity.

Collaborators

Monireh sadat seyyedsalehi-Department of medical and surgical sciences, university of Bologna-monireh.seyydsalehi@unibo.it
Paolo Boffetta-Stony Brook Cancer Center, Stony Brook University, Stony Brook NY 11794-paolo.boffetta@stonybrookmedicine.edu
Arash Etemadi-Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland-arash.etemadi@nih.gov
Farin Kamangar-Department of Biology, School of Computer, Mathematical, and Natural Sciences, Morgan State University, Baltimore, MD, USA-farinkamangar@gmail.com
Kazem Zendehdel-Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran-kzendeh@gmail.com