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Journal of Cellular and Molecular Medicine logoLink to Journal of Cellular and Molecular Medicine
. 2022 Nov 20;26(23):5794–5806. doi: 10.1111/jcmm.17595

The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake

Saeid Doaei 1, Sepideh Abdollahi 2, Golsa Khalatbari Mohseni 3, Maryam Gholamalizadeh 4, Mohammad Esmail Akbari 4, Seyed Mohammad Poorhosseini 5, Seyedeh Elaheh Bagheri 6,7, Soudeh Ghafouri‐Fard 5, Ghasem Azizi Tabesh 5, Alireza Moslem 8, Naeemeh Hasanpour Ardekanizadeh 9, Saeed Omidi 10, Azita Hekmatdoost 11, Mahdi Alam Rajabi 12, Seyed Alireza Mosavi Jarrahi 4,✉, Mark O Goodarzi 13
PMCID: PMC9716323  PMID: 36403211

Abstract

Breast cancer (BC) is the leading cause of cancer‐related deaths in females worldwide and is related to genetic and environmental factors. Dietary components may strongly influence the risk of BC. A possible association was also reported between the fat mass and obesity‐associated (FTO) single‐nucleotide polymorphisms (SNPs) and BC. This study aimed to investigate the impact of FTO rs9939609 polymorphism on the association between BC and dietary intake. This study was conducted on 180 women with BC as the case group and 360 healthy women as the control group. The dietary intakes were assessed by a valid 168‐item food frequency questionnaire (FFQ). The FTO gene was genotyped for rs9939609 polymorphism. After adjusting the confounding variables, there was no significant association between dietary intake and BC in individuals without risk allele. A positive association between dietary intake of omega‐6 fatty acids and BC was found only in individuals with risk allele of FTO gene (OR: 1.31, 95% CI: 1.08–1.60, p: 0.006). FTO gene risk allele may influence the effect of diet on breast cancer risk. Further studies are needed to assess the possible effects of the FTO genotype on the association between BC risk and dietary components.

Keywords: breast cancer, dietary intake, FTO, omega‐6 fatty acids, polymorphism

1. BACKGROUND

Breast cancer (BC) is the most prevalent cancer and is the leading cause of cancer‐related deaths in females worldwide. 1 It accounts for 1 million of about 10 million new neoplasms which are diagnosed every year worldwide. 2 The prevalence of BC in Iranian women was reported to be 23.6%. 3 An increase in the prevalence of BC is expected in the next decades along with the population ageing and exposure to cancer risk factors such as environmental carcinogens and unhealthy lifestyle. 1 , 4

Nutrition has a key role in cancer risk, and the evidence suggests that about 10%‐20 per cent of all cancer mortalities occurred due to malnutrition rather than underlying cancer. 5 , 6 Moreover, previous prospective studies indicated that there is an association between diets with low nutritional quality and an increased risk of developing chronic diseases, like cancer and obesity. 7 For instance, some food and nutrients (e.g. saturated fats, red meat and processed meat) increase the circulating levels of endogenous estrogens, insulin‐like growth factors and pro‐inflammatory cytokines, thus supporting BC development. In contrast, polyunsaturated fatty acids, vitamins C and E, fresh fruits and vegetables were reported to have protective effects against BC onset or progression. 8 , 9 Hence, nutrition and dietary components can considerably influence the risk of cancer. 6

On the contrary, BC is known as one of the most complicated diseases which is caused by a combination of environmental and genetic factors. 10 Familial aggregation of BC was also frequently reported, which indicates the key role of genetics in the development of BC. 11 Some genetic factors can influence the risk of BC. For example, several studies have documented that mutations in the BRCA1 and BRCA2 genes are responsible for hereditary BC, which accounts for 5%–10% of all BC. 11 , 12 , 13 In addition, previous studies have revealed that dysfunction of some other genes including Her2, C‐erbB‐2, c‐Myc, Cyclin, EGFR, IGF‐I and IGF‐II can lead to the initiate BC. 11 , 14 , 15

In addition, some genes such as fat mass and obesity‐associated (FTO) may have a dual effect on nutritional requirements and breast cancer risk. It has been established that the FTO gene has a role in appetite and food intake. 16 , 17 FTO gene is located on the chromosome region 16q12.2, and this gene is expressed ubiquitously with the highest expression in the liver, brain, hypothalamus and visceral fat. 18 Previous studies have reported a strong relationship between FTO genotype and body mass index (BMI), and it has been demonstrated that FTO genotypes may affect the association of dietary macronutrients with body weight and BMI. 19 , 20 , 21

On the contrary, recent studies reported that there is an association between variants of FTO including rs8050136, rs9939609, rs1477196, rs1121980, rs6499640, rs17817449, rs8047395, rs7206790 and rs11075995 polymorphisms and the risk of cancers. 22 The association between the most typical FTO SNP (rs9939609) and several cancers such as renal, lung, breast, pancreas, endometrial and prostate cancer were frequently reported. 23 , 24 , 25 , 26 The frequency of FTO gene AA genotype of rs9939609 polymorphism in male and female subjects was reported to be 12.0 and 26.0%, respectively. 27 Remarkably, it implies that the FTO variants may have an association with a broad range of diseases beyond their effect on BMI. 28 For example, the association between FTO gene polymorphisms and BC was found to be associated with the status of oestrogen receptors and PI3 K/Akt signalling pathway. 29 However, there is insufficient information to date to confirm the interplay of FTO gene and BC incidence and mortality. 30 In addition, the FTO gene–nutrition interaction as an underlying mechanism of cancer has not been well established. Therefore, this study aimed to investigate the impact of FTO polymorphism on the association between BC and dietary intake in Iranian women.

2. METHODS

2.1. Study population and data collection

A case–control study was conducted on 180 patients with cancer as the case group and 360 healthy individuals as the control group. The required sample size was estimated based on the odds ratio (OR) of the previous studies. 31 According to inclusion criteria, the participants were selected among women referred to the Cancer Research Center of Shohadaye Tajrish Hospital in Tehran, Iran. Individuals whose blood samples were collected at the beginning of the study were eligible to participate in the study according to the inclusion and exclusion criteria. For the case group, inclusion criteria were women with breast cancer, the age range of 35 to 70 years, consent of participation and recent cancer diagnosis within 3 months. For the control group, inclusion criteria were women with no malignancy, age range of 35 to 70 years and participation consent. Exclusion criteria were the inability to collect the required information and any disease that may affect the diet such as liver disease and diabetes. The case and control groups were matched by ethnicity (Persian). Basic information, including anthropometric measurements, medical history, physical activity (using the International Physical Activity Questionnaire), alcohol use, smoking, level of education and socio‐economic variables, was collected from the participants. Stadiometer was used for measuring the patient's height and weight was measured using a SECA Alpha 882 scale (SECA Corporation). Then, the patients' body mass index (BMI) was determined by dividing weight in kilograms by the square of height in metres (kg/m2).

2.2. Genotyping

Five millimetres (ml) of the blood samples of the participants was collected at the beginning of the study. The genomic deoxyribonucleic acid (DNA) was extracted from the blood samples using GeneAll DNA extraction kit (Incheon, Korea) following the manufacturer's instruction. Extracted DNA samples were amplified using PCR and master mix DNA polymerase (cat. No A180301; Ampliqon, Denmark). The FTO gene polymorphism rs9939609 was assessed using the tetra‐primer amplification refractory mutation system‐polymerase chain (Tetra‐ARMS PCR) technique using the PCR products. The sequences for the primers are presented in Supplementary file 1.

2.3. Dietary intake

The intake of macronutrients, micronutrients and calories was evaluated using a valid 168‐item FFQ consisted of 168 food items with standard portion sizes commonly consumed by Iranian people. Face‐to‐face interviews were administered by a trained dietitian. Data on food intake during the last year in the control group and related to food intake in the last year before cancer diagnosis in the case group were collected. All reported consumption frequencies were converted to grams per day by using household measures. Then, these data were used to determine macro and micronutrient intake by the Nutritionist IV software (version 7.0; N‐Squared Computing, Salem, OR, USA).

2.4. Statistical analysis

The participants in the two groups were compared in terms of demographic and pathological conditions by the independent t‐test and qi‐square test for quantitative and qualitative variables, respectively. The normal distribution of data was examined by the Kolmogorov–Smirnov test. The odds ratio of the association between BC and dietary components in people with different genotypes of the FTO gene was determined using logistic regression by adjusting the effect of confounding variables in different models: Model 1: adjusted for age, breast feeding duration, first menstruation age, post‐menopause age, breast cancer family history, number of pregnancies, smoking, using alcohol drinks and physical activity, and model 2: further adjustments for BMI. A dominant genetic model was used due to the low minor allele frequency (MAF) values. All analyses were performed using SPSS software (version 22.0; IBM Corp., Armonk, NY, USA) at a significance level of 0.05. The Hardy–Weinberg equation was used to calculate the allelic frequency in the studied population.

3. RESULTS

All variables were normally distributed. The average age of the cases and controls was 65 ± 27 and 68 ± 29 (p = 0.06), and the mean BMI of these groups was 29 ± 3.9 and 27 ± 2.8 kg/m2 (p < 0.01), respectively. The number of pregnancies and the rate of breastfeeding months were significantly lower, and the family history of BC was significantly higher in the case group compared with the control group (p = 0.01) (Table 1). Regarding the genotype of rs9939609 polymorphism of the FTO gene, no significant difference was found between the two groups in the dominant genetic model (AA and AT vs. TT) (p = 0.46). Based on the Hardy–Weinberg equation, allelic frequencies of A and T were 0.4 and 0.6, respectively. Also, there was no significant difference concerning the first menstrual age, menopausal age, smoking rate, alcohol consumption and physical activity between the groups.

TABLE 1.

Characteristics and dietary intake of the participants

Variables Cases (n = 180) Controls (n = 360) p
Age (y) 68 ± 29 65 ± 27 0.06
Height (cm) 156 ± 5 161 ± 6 0.01
Weight (kg) 71 ± 11 71 ± 10 0.86
BMI (kg/m2) 29.19 ± 3.91 27.27 ± 2.87 0.01
Breast feeding duration (month) 34 ± 29 59 ± 33 0.01
First menstruation Age (year) 13 ± 2 13 ± 2 0.51
Age of menopause (year) 47 ± 5 47 ± 5 0.89
Breast cancer family history (yes) 35% 14% 0.01
Number of pregnancies (n) 3 ± 2 4 ± 2 0.01
Smoking (yes) 2.9% 5% 0.34
Using alcohol drinks (yes) 98.5% 99.2% 0.62
Physical activity (hr/d) 2 ± 4.5 1.5 ± 1.5 0.51
Genotype
TT 31% 35% 0.79
AT 58% 56%
AA 11% 9%
Calorie intake (Kcal/d) 2737 ± 925 2315 ± 1.066 0.01
Protein (g/d) 86.63 ± 41.572 84.93 ± 41.744 0.81
Carbohydrate (g/d) 402.1 ± 124 311.6 ± 170 <0.01
Total fat (g/d) 92.90 ± 42.277 93.34 ± 52.885 0.96
Cholesterol (mg/d) 2.420 ± 130 2.327 ± 161 0.71
Saturated fat (g/d) 2.929 ± 18.892 2.522 ± 13.006 0.12
MUFA (g/d) 3.049 ± 13.343 3.503 ± 24.546 0.19
PUFA (g/d) 1.941 ± 8.563 1.903 ± 12.364 0.83
Omega‐3 fatty acids (g/d) 1.253 ± 0.557 1.011 ± 1.033 0.09
Omega‐6 fatty acids (g/d) 5.452 ± 6.992 0.399 ± 0.586 <0.01
Sodium (mg/d) 5.661 ± 2.559 4.935 ± 4.288 0.23
Potassium (mg/d) 4.083 ± 1.829 4.635 ± 4.909 0.39
Vitamin A (RAE/d) 4.851 ± 265 8.767 ± 1.949 0.12
Beta carotene (μg/d) 3.116 ± 1.967 7.271 ± 2.316 0.16
Alpha carotene (μg/d) 5.435 ± 607 3.892 ± 3.048 0.32
Lutein (μg/d) 1.551 ± 794 2.385 ± 7.801 0.40
β‐Cryptoxanthin (μg/d) 2.973 ± 176 3.651 ± 495 0.30
Lycopene (μg/d) 7.620 ± 4.582 4.592 ± 9.664 0.02
Vitamin C (mg/d) 1.507 ± 113 2.179 ± 278 0.07
Calcium (mg/d) 1.277 ± 1.011 1.198 ± 674 0.57
Iron (mg/d) 19.78 ± 6.477 15.41 ± 12.131 0.01
Vitamin D (μg/d) 1.051 ± 0.842 1.794 ± 1.565 <0.01
Vitamin E (mg/d) 1.768 ± 11.446 1.746 ± 11.606 0.91
Alpha tocopherol (mg/d) 1.160 ± 7.650 1.286 ± 11.613 0.45
Thiamin (mg/d) 2.364 ± 0.962 1.555 ± 0.756 <0.01
Riboflavin (mg/d) 2.310 ± 1.372 2.183 ± 1.319 0.57
Niacin (mg/d) 2.431 ± 7.929 1.821 ± 9.212 <0.01
Vitamin B6 (mg/d) 1.823 ± 0.787 2.082 ± 1.188 0.13
Folate (μg/d) 6.735 ± 2.05 4.654 ± 3.08 <0.01
Vitamin B12 (μg/d) 3.933 ± 3.765 4.679 ± 3.138 0.19
Biotin (μg/d) 3.119 ± 14.816 3.198 ± 16.869 0.77
Pantothenic (mg/d) 5.311 ± 2.691 5.897 ± 2.547 0.18
Vitamin K (μg/d) 1.243 ± 55.014 3.995 ± 2.019 0.28
Phosphorus (mg/d) 1.450 ± 948 4.248 ± 3.275 0.32
Magnesium (mg/d) 3.822 ± 159 4.480 ± 379 0.20
Zinc (mg/d) 1.136 ± 6.041 1.280 ± 6.936 0.19
Copper (mg/d) 1.913 ± 0.606 1.838 ± 1.518 0.71
Manganese (mg/d) 5.772 ± 2.634 4.902 ± 3.724 0.12
Selenium (mg/d) 9.877 ± 40.823 8.259 ± 41.753 0.02
Fluoride (mg/d) 3.374 ± 1.882 5.286 ± 824 <0.01
Chromium (mg/d) 0.022 ± 0.089 0.071 ± 0.067 <0.01
Total fibre (g/d) 2.918 ± 11.318 3.232 ± 26.592 0.38
Soluble fibre (g/d) 1.055 ± 0.824 1.119 ± 2.316 0.83
Insoluble fibre (g/d) 5.421 ± 3.779 1.383 ± 1.062 0.32
Crude fibre (g/d) 1.139 ± 6.651 3.270 ± 42.434 <0.01
Sugar total (g/d) 1.430 ± 64.130 1.607 ± 92.727 0.19
Glucose (g/d) 2.150 ± 8.937 2.164 ± 15.959 0.95
Galactose (g/d) 4.293 ± 8.866 4.314 ± 3.317 0.99
Fructose (g/d) 2.711 ± 11.156 2.210 ± 16.627 0.04
Sucrose (g/d) 4.913 ± 27.130 5.899 ± 59.303 0.22
Lactose (g/d) 1.485 ± 24.062 1.632 ± 11.146 0.62
Maltose (g/d) 2.989 ± 1.551 1.024 ± 0.802 <0.01
Caffeine (mg/d) 1.876 ± 111 2.848 ± 49.043 <0.01
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Abbreviations: BMI, body mass index; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids.

Regarding the dietary intake of the groups, the results showed that the intake of calories (2737 ± 925 vs. 2315 ± 1.066 kcal/d, p = 0.01), carbohydrates (402.1 ± 124 vs. 311.6 ± 170 g/d, p < 0.01), omega‐6 fatty acids (5.452 ± 6.992 vs. 0.399 ± 0.586 g/d, p < 0.01), iron (19.78 ± 6.477 vs. 1.541 ± 12.131 mg/d, p = 0.01), thiamine (2.364 ± 0.962 vs. 1.555 ± 0.756 mg/d, p < 0.01), niacin (2.431 ± 7.929 vs. 1.821 ± 9.212 mg/d, p < 0.01), folate (6.735 ± 2.05 vs. 4.654 ± 3.08 μg/d, p < 0.01) and maltose (2.989 ± 1.551 vs. 1.024 ± 0.802 g/d, p < 0.01) was higher in cancer patients compared with healthy individuals. On the contrary, the intake of vitamin D (1.794 ± 1.565 vs. 1.051 ± 0.842 μg/d, p < 0.01), fluoride (5.286 ± 824 vs. 3.374 ± 1.882 mg/d, p < 0.01), chromium (0.071 ± 0.067 vs. 0.022 ± 0.089 mg/d, p < 0.01), crude fibre (3.270 ± 42.434 vs. 1.139 ± 6.651 g/d, p < 0.01) and caffeine (2.848 ± 49.043 vs. 1.876 ± 111 mg/d, p < 0.01) in healthy individuals was higher than in patients with breast cancer (Table 1).

In terms of dietary intake between case and control groups with TT genotype of FTO rs9939609 polymorphism, results showed that intake of cholesterol (288.23 ± 137.27 vs. 176.12 ± 95.90 mg/d, p < 0.01), saturated fatty acids (29.61 ± 10.67 vs. 19.60 ± 6.50 g/d, p < 0.01), omega‐6 fatty acids (7.36 ± 5.80 vs. 1.42 ± 2.75 g/d, p < 0.01), vitamin B12 (4.94 ± 2.37 vs. 3.25 ± 1.80 μg/d, p = 0.01), phosphorus (200.97 ± 20.69 vs. 15.69 ± 87.64 mg/d, p < 0.01), fluoride (2736 ± 1604 vs. 479 ± 631 mg/d, p < 0.01), maltose (2.30 ± 1.26 vs. 1.09 ± 1.24 g/d, p = 0.01) and caffeine (180.17 ± 90.34 vs. 19.25 ± 36.11 mg/d, p < 0.01) in the case group was higher than in the control group (Table 2).

TABLE 2.

Dietary intake between case and control groups with different genotypes

Variables TT genotypes p AA/AT genotypes p
Cases (N = 56) Controls (n = 126) Cases (n = 124) Controls (n = 234)
Calorie intake (Kcal/d) 2589.57 ± 444.45 2261.98 ± 1146.99 0.39 2590.62 ± 507.86 2285.58 ± 1073.11 0.13
Protein (g/d) 84.78 ± 20.61 76.53 ± 43.22 0.56 83.38 ± 27.26 84.97 ± 44.93 0.84
Carbohydrate (g/d) 366.38 ± 70.89 337.47 ± 218.47 0.68 372.88 ± 63.24 301.67 ± 145.42 0.01
Total fat (g/d) 94.84 ± 20.15 94.43 ± 63.09 0.98 93.34 ± 24.07 91.40 ± 54.68 0.84
Cholesterol (mg/d) 288.23 ± 137.27 176.12 ± 95.90 <0.01 269.01 ± 141.72 225.15 ± 195.02 0.23
Saturated fat (g/d) 29.61 ± 10.67 19.60 ± 6.50 <0.01 29.67 ± 14.20 23.76 ± 12.66 0.02
MUFA (g/d) 34.60 ± 12.66 27.59 ± 14.81 0.17 33.25 ± 13.53 35.47 ± 28.84 0.67
PUFA (g/d) 20.43 ± 8.13 17.25 ± 9.89 0.34 18.96 ± 7.39 19.81 ± 13.01 0.72
Omega‐3 fatty acids (g/d) 1.33 ± 0.77 0.89 ± 0.59 0.05 1.24 ± 0.66 1.06 ± 1.11 0.39
Omega‐6 fatty acids (g/d) 7.36 ± 5.80 1.42 ± 2.75 <0.01 5.89 ± 5.45 0.88 ± 2.19 <0.01
Sodium (mg/d) 7077.65 ± 4645.62 6259.05 ± 3708.26 0.53 7418.36 ± 4202.02 5096.98 ± 4993.16 0.02
Potassium (mg/d) 5954.96 ± 4182.45 4500.51 ± 3640.31 0.28 5746.37 ± 3745.77 4976.15 ± 6619.09 0.53
Vitamin A (RAE/d) 681.41 ± 335.02 2351.18 ± 4773.37 0.29 657.98 ± 348.75 572.31 ± 379.46 0.25
Beta carotene (μg/d) 4750.26 ± 2726.77 25,909.97 ± 56,766.04 0.26 5010.22 ± 3046.66 3587.30 ± 3595.60 0.04
Alpha carotene (μg/d) 40,774.63 ± 50,738.50 274,498.71 ± 811,824.32 0.41 53,677.41 ± 61,803.93 3860.02 ± 19,669.38 <0.01
Lutein (μg/d) 1993.25 ± 1263.85 7510.44 ± 19,582.08 0.39 2156.89 ± 1294.91 1244.35 ± 968.15 <0.01
β‐Cryptoxanthin (μg /d) 467.35 ± 303.56 483.30 ± 592.36 0.93 441.01 ± 316.97 318.39 ± 359.36 0.08
Lycopene (μg/d) 9864.12 ± 6643.26 13,902.81 ± 22,504.58 0.60 9916.71 ± 7174.19 2293.30 ± 3512.05 <0.01
Vitamin C (mg/d) 196.20 ± 121.10 416.61 ± 554.12 0.24 195.09 ± 136.63 187.80 ± 185.54 0.83
Calcium (mg/d) 1239.57 ± 413.14 1275.67 ± 1212.01 0.92 1308.93 ± 710.95 1096.57 ± 541.63 0.05
Iron (mg/d) 18.63 ± 4.70 21.69 ± 23.96 0.69 18.18 ± 4.49 14.62 ± 8.21 0.02
Vitamin D (μg/d) 2.04 ± 1.43 1.40 ± 1.39 0.21 1.91 ± 1.27 1.77 ± 1.50 0.63
Vitamin E (mg/d) 19.17 ± 9.69 21.32 ± 22.47 0.77 16.81 ± 8.75 17.23 ± 8.22 0.79
Alpha tocopherol (mg/d) 13.02 ± 6.22 17.28 ± 24.98 0.60 11.66 ± 5.78 12.22 ± 7.18 0.68
Thiamin (mg/d) 2.07 ± 0.58 1.60 ± 0.91 0.14 2.13 ± 0.67 1.62 ± 0.85 <0.01
Riboflavin (mg/d) 2.27 ± 0.65 2.60 ± 2.90 0.72 2.30 ± 0.94 1.99 ± 0.75 0.04
Niacin (mg/d) 21.48 ± 6.74 18.07 ± 14.35 0.47 21.74 ± 7.88 19.56 ± 8.94 0.20
Vitamin B6 (mg/d) 1.82 ± 0.53 2.76 ± 2.48 0.26 1.91 ± 0.63 1.87 ± 0.68 0.71
Folate total (g/d) 596.88 ± 179.82 514.82 ± 405.19 0.54 614.36 ± 155.08 480.06 ± 346.32 0.04
Folate DFE (μg/d) 699.65 ± 230.28 568.51 ± 451.45 0.38 721.58 ± 213.84 493.01 ± 371.46 <0.01
Vitamin B12 (μg/d) 4.94 ± 2.37 3.25 ± 1.80 0.01 4.40 ± 3.32 4.67 ± 3.27 0.67
Biotin (μg/d) 30.69 ± 11.64 38.80 ± 27.92 0.38 31.76 ± 12.95 29.34 ± 11.65 0.29
Pantothenic (mg/d) 5.51 ± 1.61 5.58 ± 3.54 0.94 5.61 ± 1.91 5.81 ± 2.41 0.65
Vitamin K (μg/d) 306.17 ± 265.19 1757.50 ± 5096.46 0.39 312.55 ± 231.58 132.62 ± 151.62 <0.01
Phosphorus (mg/d) 200.97 ± 20.69 15.69 ± 87.64 <0.01 155,502.93 ± 188,116.67 17,395.97 ± 86,793.14 <0.01
Magnesium (mg/d) 404.39 ± 108.80 614.56 ± 818.89 0.43 413.93 ± 110.34 404.66 ± 238.94 0.83
Zinc (mg/d) 12.20 ± 4.44 12.59 ± 7.73 0.87 11.74 ± 4.64 12.59 ± 6.48 0.48
Copper (mg/d) 1.92 ± 0.51 2.38 ± 2.94 0.63 1.83 ± 0.53 1.73 ± 1.18 0.63
Manganese (mg/d) 5.73 ± 1.67 6.29 ± 7.23 0.81 5.78 ± 1.78 4.96 ± 3.16 0.16
Selenium (mg/d) 99.44 ± 31.87 82.07 ± 49.09 0.29 98.48 ± 34.53 87.68 ± 50.12 0.25
Fluoride (mg/d) 2.74 ± 1604 4.79 ± 631 <0.01 3.09.80 ± 1800.11 4.79 ± 614.69 <0.01
Chromium (mg/d) 0.06 ± 0.06 0.08 ± 0.11 0.66 0.07 ± 0.07 0.08 ± 0.08 0.55
Total Fibre (g/d) 30.20 ± 14.24 40.40 ± 44.04 0.48 31.24 ± 13.87 32.28 ± 26.25 0.83
Soluble fibre (g/d) 1.93 ± 1.49 1.14 ± 1.36 0.11 1.99 ± 1.52 0.8 ± 0.69 <0.01
Insoluble fibre (g/d) 584.13 ± 747.25 951.86 ± 2832.80 0.70 623.26 ± 746.69 13.02 ± 44.43 <0.01
Crude fibre (g/d) 29.81 ± 26.56 30.29 ± 30.98 0.96 35.17 ± 29.88 40.76 ± 55.09 0.60
Sugar total (g/d) 145.23 ± 50.55 159.73 ± 105.80 0.67 148.96 ± 47.35 155.23 ± 80.62 0.67
Glucose (g/d) 19.56 ± 10.05 24.59 ± 20.94 0.47 21.35 ± 10.78 21.13 ± 16.10 0.94
Galactose (g/d) 4.41 ± 3.02 3.07 ± 2.24 0.12 5.11 ± 6.63 4.38 ± 3.96 0.41
Fructose (g/d) 23.43 ± 11.64 26.29 ± 23.50 0.71 24.83 ± 12.55 21.51 ± 16.16 0.28
Sucrose (g/d) 57.20 ± 37.54 49.45 ± 59.31 0.66 55.53 ± 31.11 60.08 ± 51.82 0.63
Lactose (g/d) 16.38 ± 9.72 12.20 ± 11.20 0.30 16.87 ± 17.86 16.48 ± 10.92 0.87
Maltose (g/d) 2.30 ± 1.26 1.09 ± 1.24 0.01 2.34 ± 1.34 1.25 ± 0.93 <0.01
Caffeine (mg/d) 180.17 ± 90.34 19.25 ± 36.11 <0.01 184.33 ± 99.20 23.17 ± 36.34 <0.01
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Abbreviations: MUFA, monounsaturated fatty acids, PUFA, polyunsaturated fatty acids.

Regarding dietary intake between case and control groups with AA/AT genotype of FTO rs9939609 polymorphism, results showed that intake of carbohydrates (372 ± 63 vs. 301 ± 145 g/d, p = 0.01), saturated fat (29.67 ± 14.20 vs. 23.76 ± 12.66 g/d, p = 0.02), omega‐6 (5.89 ± 5.45 vs. 0.88 ± 2.19 g/d, p < 0.01), sodium (7418 ± 4202 vs. 5096 ± 4993 mg/d, p = 0.02), beta‐carotene (5010 ± 3046 vs.3587 ± 3595 μg/d, p = 0.04), alpha‐carotene (53,677 ± 61,803 vs. 3860 ± 1966 μg/d, p < 0.01), lutein (2156 ± 1249 vs. 1244 ± 968 μg/d, p < 0.01), lycopene (9916 ± 7174, vs. 2293 ± 3512 μg/d, p < 0.01), iron (18.18 ± 4.49 vs. 14.62 ± 8.21 mg/d, p = 0.02), thiamin (2.13 ± 0.67 vs. 1.62 ± 0.85 mg/d, p < 0.01), riboflavin (2.30 ± 0.94 vs. 1.99 ± 0.75 mg/d, p = 0.04), folate (614 ± 155 vs. 480 ± 346 μg/d, p = 0.04), vitamin K (312 ± 231 vs. 132 ± 151 μg/d, p < 0.01), phosphorus (155 ± 188 vs. 173 ± 867 mg/d, p < 0.01), fluoride (3087 ± 1800 vs. 479 ± 614 μg/d, p < 0.01), soluble fibre (1.99 ± 1.52 vs. 0.8 ± 0.69 g/d, p < 0.01), insoluble fibre (623 ± 746 vs. 13 ± 44 g/d, p < 0.01), maltose (2.34 ± 1.34 vs. 1.25 ± 0.93 g/d, p < 0.01) and caffeine (184 ± 99 vs. 23 ± 36 mg/d, p < 0.01) was higher in case of the group compared with the control group (Table 2).

After considering the FTO genotype differences between the groups, the results indicated that the amount of nutrients intake in individuals with one or two risk alleles in each of the two groups was not significantly different from those without risk alleles (Table 3).

TABLE 3.

Comparison of food intake in individuals with polymorphism with those without polymorphism in case and control groups

Variables Cases (n = 180) p Controls (n = 360) p
TT AA & AT TT AA & AT
Calorie intake (Kcal/d) 2743 ± 922 2792 ± 1.064 0.85 2258 ± 1.216 2263 ± 1.106 0.99
Protein (g/d) 82.0 ± 34.626 88.47 ± 51.611 0.83 7951 ± 44.743 8521 ± 46.091 0.75
Carbohydrate (g/d) 397.0 ± 144 411.8 ± 125 0.68 336.9 ± 231 296.9 ± 149 0.64
Total fat (g/d) 96.81 ± 41.034 93.47 ± 49.936 0.77 95.66 ± 66.801 90.93 ± 56.571 0.85
Cholesterol (mg/d) 261.6 ± 125 234.1 ± 144 0.43 192.0 ± 86.532 230.1 ± 200 0.43
Saturated fat (g/d) 29.52 ± 13.553 30.14 ± 24.541 0.90 18.81 ± 6.372 23.65 ± 12.953 0.14
MUFA (g/d) 3154 ± 13.117 3074 ± 15.298 0.83 2918 ± 14.774 3583 ± 29.730 0.38
PUFA (g/d) 2142 ± 10.072 1873 ± 8.515 0.29 1615 ± 9.829 1990 ± 13.293 0.37
Omega‐3 fatty acids (g/d) 1397 ± 0.698 1213 ± 0.530 0.28 0811 ± 0.570 1047 ± 1.127 0.41
Omega‐6 fatty acids (g/d) 6486 ± 7.931 5450 ± 7.519 0.61 0602 ± 0.944 0331 ± 0.410 0.42
Sodium (mg/d) 5237 ± 2.333 5610 ± 2.390 0.55 5615 ± 3.286 4682 ± 4.871 0.52
Potassium (mg/d) 4271 ± 1.890 4114 ± 2.121 0.76 4500 ± 3.640 5052 ± 6.841 0.76
Vitamin A (RAE/d) 5291 ± 248 4823 ± 308 0.51 2550 ± 5.018 5591 ± 379 0.27
Beta carotene (μg/d) 3154 ± 1.751 3265 ± 2.373 0.83 2826 ± 5.968 3261 ± 3.176 0.24
Alpha carotene (μg/d) 5190 ± 521 6219 ± 745 0.52 2744 ± 8.118 2902 ± 387 0.34
Lutein (μg/d) 1426 ± 578 1644 ± 913 0.25 8115 ± 2.067 1210 ± 888 0.35
β‐Cryptoxanthin (μg/d) 3034 ± 187 2923 ± 179 0.82 4885 ± 628 3045 ± 363 0.42
Lycopene (μg/d) 7997 ± 4.444 6806 ± 4.261 0.30 1390 ± 2.250 1977 ± 3.109 0.15
Vitamin C (mg/d) 1789 ± 82.964 1485 ± 146 0.29 4314 ± 585 1805 ± 184 0.24
Calcium (mg/d) 1265 ± 612 1357 ± 1.361 0.71 1349 ± 1.261 1122 ± 538 0.61
Iron (mg/d) 1931 ± 6.970 1980 ± 6.262 0.78 2147 ± 25.410 1426 ± 8.269 0.43
Vitamin D (μg/d) 1331 ± 1.015 0994 ± 0.787 0.18 1400 ± 1.391 1837 ± 1.534 0.44
Vitamin E (mg/d) 1966 ± 12.848 1753 ± 12.312 0.52 2117 ± 23.831 1675 ± 8.276 0. 60
Alpha tocopherol (mg/d) 1308 ± 8.649 1130 ± 8.132 0.42 1795 ± 26.405 1203 ± 7.386 0.52
Thiamin (mg/d) 2233 ± 0.873 2463 ± 1.086 0.36 1489 ± 0.884 1596 ± 0.868 0.76
Riboflavin (mg/d) 2317 ± 1.064 2413 ± 1.752 0.79 2701 ± 3.066 2011 ± 0.766 0.52
Niacin (mg/d) 2297 ± 7.712 2481 ± 7.958 0.37 1701 ± 14.802 1915 ± 9.067 0.69
Vitamin B6 (mg/d) 1820 ± 0.652 1888 ± 0.970 0.74 2871 ± 2.608 1829 ± 0.680 0.27
Folate total (g/d) 6721 ± 244 6824 ± 197 0.86 5158 ± 429 4766 ± 358 0.81
Folate DFE (μg/d) 8056 ± 299 8341 ± 291 0.72 5642 ± 478 4848 ± 383 0.66
Vitamin B12 (μg/d) 4078 ± 1.999 4188 ± 5.095 0.90 3238 ± 1.914 4688 ± 3.336 0.12
Biotin (μg/d) 3335 ± 12.539 3077 ± 17.258 0.50 3943 ± 29.547 2891 ± 11.703 0.33
Pantothenic (mg/d) 5359 ± 2.298 5415 ± 3.327 0.94 5701 ± 3.745 5810 ± 2.504 0.94
Vitamin K (μg/d) 1268 ± 50.526 1264 ± 60.966 0.98 1926 ± 5.375 1258 ± 149 0.34
Phosphorus (mg/d) 1424 ± 646 1521 ± 1.247 0.68 1500 ± 877 1550 ± 742 0.88
Magnesium (mg/d) 3796 ± 162 3840 ± 167 0.92 6266 ± 867 4110 ± 245 0.48
Zinc (mg/d) 1109 ± 5.806 1141 ± 6.619 0.84 1205 ± 8.008 1236 ± 6.566 0.92
Copper (mg/d) 1942 ± 0.648 1896 ± 0.598 0.78 2385 ± 3.125 1780 ± 1.207 0.58
Manganese (mg/d) 5323 ± 1.796 5810 ± 1.917 0.32 5779 ± 7.472 4941 ± 3.237 0.75
Selenium (mg/d) 9151 ± 33.884 1019 ± 38.551 0.27 7071 ± 35.478 8576 ± 51.306 0.33
Fluoride (mg/d) 3313 ± 1.549 3272 ± 1.675 0.92 4795 ± 631 4.283 ± 539 0.83
Chromium (mg/d) 0003 ± 0.007 0.026 ± 0.074 0.06 0049 ± 0.041 0.083 ± 0.084 0.13
Total Fibre (g/d) 3150 ± 14.805 2896 ± 9.109 0.46 4079 ± 46.697 3265 ± 26.468 0.63
Soluble fibre (g/d) 1204 ± 1.174 1045 ± 0.648 0.55 1265 ± 1.390 0784 ± 0.673 0.34
Insoluble fibre (g/d) 5855 ± 4.914 5600 ± 3.467 0.83 9518 ± 2.832 4975 ± 5.471 0.35
Crude fibre (g/d) 1153 ± 6.458 1142 ± 6.039 0.95 3029 ± 30.988 4076 ± 55.091 0.48
Sugar total (g/d) 1458 ± 73.343 1469 ± 65 0.95 1622 ± 111 1538 ± 83.192 0.84
Glucose (g/d) 2189 ± 9.356 21,924 ± 9.857 0.99 2422 ± 22.183 2129 ± 16.623 0.72
Galactose (g/d) 4019 ± 3.233 4986 ± 12.405 0.64 3075 ± 2.249 4428 ± 4.024 0.21
Fructose (g/d) 2811 ± 12.866 2722 ± 11.563 0.79 2723 ± 24.730 2168 ± 16.588 0.54
Sucrose (g/d) 5311 ± 34.881 4777 ± 23.931 0.52 5371 ± 54.719 5817 ± 52.808 0.83
Lactose (g/d) 1528 ± 10.686 1647 ± 33.355 0.84 1220 ± 11.208 1650 ± 11.117 0.33
Maltose (g/d) 2827 ± 1.478 3062 ± 1.707 0.57 0734 ± 0.538 1199 ± 0.926 0.07
Caffeine (mg/d) 1801 ± 90.340 1843 ± 99.203 0.87 1925 ± 36.116 2317 ± 36.344 0.78
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Note: Adjusted for age, BMI, breast feeding duration, first menstruation age, post‐menopause age, breast cancer family history, number of pregnancies, smoking, using alcohol drinks and physical activity.

Abbreviations: MUFA, monounsaturated fatty acids, PUFA, polyunsaturated fatty acids.

The results of logistic regression of the association between BC and dietary intake regardless of FTO genotypes showed that there was a significant association between dietary intake of calorie (OR: 1.01, 95% CI: 1.00–1.02, p: 0.04) and omega‐6 fatty acids (OR: 1.25, 95% CI: 1.14–1.38, p < 0.01) (Table 4). Moreover, the results of logistic regression of the association between BC and dietary intake based on FTO genotype showed that there was no significant association between dietary intake and BC in individuals without risk allele after adjusting confounding variables including age, breastfeeding duration, first menstruation age, post‐menopause age, breast cancer family history, number of pregnancies, smoking, using alcohol drinks and physical activity (Model 1). Further adjustment for BMI did not change the results (Model 2) (Table 5).

TABLE 4.

Logistic regression of the association between breast cancer and dietary intake

Variables OR (CI 95%) p
Calorie intake 1.01 (1–1.02) 0.04
Protein 0.94 (0.89–1.00) 0.05
Carbohydrate 0.97 (0.93–1.00) 0.24
Total fat 0.91 (0.83–1.00) 0.06
Cholesterol 1.00 (0.99–1.00) 0.65
Saturated fat 0.98 (0.93–1.00) 0.60
MUFA 0.99 (0.95–1.00) 0.76
PUFA 0.99 (0.91–1.00) 0.82
Omega‐3 fatty acids 1.38 (0.68–2.81) 0.37
Omega‐6 fatty acids 1.25 (1.14–1.38) <0.01
Sodium 1.00 (1.00–1.00) 0.82
Potassium 1.00 (1.00–1.00) 0.53
Vitamin A 0.99 (0.99–1.00) 0.45
Beta carotene 1.00 (1.00–1.00) 0.43
Alpha carotene 1.00 (1.00–1.00) 0.54
Lutein 1.00 (1.00–1.00) 0.38
β‐Cryptoxanthin 0.99 (0.99–1.00) 0.49
Lycopene 1.00 (1.00–1.00) 0.16
Vitamin C 1.00 (0.99–1.00) 0.77
Calcium 1.00 (0.99–1.00) 0.88
Iron 0.96 (0.80–1.15) 0.68
Vitamin D 1.17 (0.85–1.59) 0.32
Vitamin E 0.90 (0.80–1.02) 0.10
Alpha tocopherol 1.00 (0.84–1.19) 0.95
Thiamin 1.19 (0.22–6.27) 0.83
Riboflavin 1.01 (0.29–3.45) 0.98
Niacin 1.01 (0.94–1.08) 0.76
Vitamin B6 0.90 (0.32–2.50) 0.84
Folate total 1.00 (0.99–1.01) 0.73
Folate DFE 0.99 (0.99–1.00) 0.62
Vitamin B12 1.01 (0.83–1.22) 0.90
Biotin 1.03 (0.98–1.07) 0.18
Pantothenic 0.80 (0.54–1.20) 0.28
Vitamin K 1.00 (0.99–1.00) 0.96
Phosphorus 1.00 (1.00–1.00) 0.11
Magnesium 0.99 (0.98–1.00) 0.66
Zinc 0.97 (0.83–1.12) 0.69
Copper 1.53 (0.34–6.84) 0.57
Manganese 0.75 (0.49–1.13) 0.17
Selenium 1.00 (0.97–1.02) 0.99
Fluoride 1.00 (1.00–1.01) 0.75
Chromium 16.17 (0.01–27) 0.46
Total fibre 1.01 (0.95–1.07) 0.64
Soluble fibre 1.29 (0.99–1.69) 0.05
Insoluble fibre 1.00 (0.99–1.00) 0.98
Crude fibre 1.00 (0.98–1.02) 0.68
Sugar total 0.99 (0.97–1.00) 0.20
Glucose 0.99 (0.95–1.03) 0.71
Galactose 1.02 (0.90–1.16) 0.68
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Abbreviations: MUFA, monounsaturated fatty acids, PUFA, polyunsaturated fatty acids.

TABLE 5.

Logistic regression of the association between breast cancer and dietary intake in individuals with (AA/AT) and without risk allele (TT) of rs9939609 FTO gene polymorphism

Variables TT genotype AA/AT genotype
Model 1 Model 2 Model 1 Model 2
OR (CI 95%) p OR (CI 95%) p OR (CI 95%) p OR (CI 95%) p
Calorie intake 1.01 (0.96–1.05) 0.66 0.99 (0.94–1.05) 0.91 1.01 (0.99–1.03) 0.25 1.01 (0.98–1.03) 0.34
Protein 0.94 (0.72–1.21) 0.63 0.96 (0.70–1.33) 0.84 0.88 (0.77–1.01) 0.07 0.86 (0.74–1.01) 0.08
Carbohydrate 0.97 (0.82–1.15) 0.77 1.01 (0.81–1.27) 0.87 0.97 (0.89–1.06) 0.57 0.99 (0.89–1.10) 0.86
Total fat 0.90 (0.60–1.35) 0.62 0.98 (0.58–1.66) 0.95 0.91 (0.75–1.11) 0.39 0.92 (0.72–1.18) 0.55
Cholesterol 0.99 (0.98–1.01) 0.51 0.99 (0.97–1.01) 0.41 1.00 (0.99–1.00) 0.14 1.00 (0.99–1.01) 0.07
Saturated fat 0.92 (0.73–1.15) 0.47 0.95 (0.72–1.25) 0.74 0.95 (0.84–1.08) 0.47 0.89 (0.76–1.04) 0.15
MUFA 0.99 (0.83–1.19) 0.98 0.97 (0.76–1.25) 0.86 0.99 (0.90–1.08) 0.89 0.97 (0.87–1.09) 0.71
PUFA 1.08 (0.73–1.59) 0.69 1.17 (0.71–1.92) 0.52 1.03 (0.86–1.23) 0.72 0.93 (0.74–1.17) 0.57
Omega‐3 fatty acids 3.68 (0.11–118/6) 0.46 2.64 (0.02–269‐89) 0.68 0.68 (0.13–3.51) 0.64 1.05 (0.12–8.95) 0.95
Omega‐6 fatty acids 1.40 (0.89–2.20) 0.14 1.39 (0.85–2.27) 0.18 1.31 (1.08–1.60) <0.01 1.26 (1.00–1.59) 0.04
Sodium 1.00 (1.00–1.00) 0.82 1.00 (1.00–1.00) 0.86 1.00 (1.00–1.00) 0.27 1.00 (1.00–1.00) 0.51
Potassium 1.00 (1.00–1.00) 0.52 1.00 (1.00–1.00) 0.28 1.00 (1.00–1.00) 0.97 1.00 (1.00–1.00) 0.40
Vitamin A 0.99 (0.99–1.00) 0.85 0.99 (0.98–1.00) 0.87 1.00 (0.99–1.00) 0.92 1.00 (0.99–1.00) 0.91
Beta carotene 0.99 (0.99–1.00) 0.26 0.99 (0.99–1.00) 0.33 1.00 (0.99–1.00) 0.28 1.00 (0.99–1.00) 0.13
Alpha carotene 1.00 (1.00–1.00) 0.90 1.00 (1.00–1.00) 0.91 1.00 (1.00–1.00) 0.64 1.00 (1.00–1.00) 0.43
Lutein 1.00 (0.99–1.00) 0.25 1.00 (0.99–1.00) 0.21 1.00 (1.00–1.00) 0.26 1.00 (0.99–1.00) 0.59
β‐Cryptoxanthin 1.00 (0.99–1.00) 0.94 1.00 (0.99–1.00) 0.90 0.99 (0.99–1.00) 0.25 0.99 (0.99–1.00) 0.64
Lycopene 1.00 (1.00–1.00) 0.82 1.00 (1.00–1.00) 0.65 1.00 (1.00–1.00) 0.18 1.00 (1.00–1.00) 0.22
Vitamin C 1.00 (0.98–1.01) 0.96 0.99 (0.97–1.01) 0.61 0.99 (0.99–1.00) 0.76 0.99 (0.99–1.00) 0.58
Calcium 0.99 (0.98–1.00) 0.55 0.99 (0.98–1.00) 0.54 1.00 (0.99–1.00) 0.64 1.00 (0.99–1.00) 0.62
Iron 1.46 (0.56–3.82) 0.43 1.52 (0.40–5.83) 0.53 0.97 (0.64–1.47) 0.90 0.96 (0.57–1.61) 0.85
Vitamin D 1.10 (0.22–4.76) 0.89 1.51 (0.23–9.98) 0.66 1.53 (0.75–3.11) 0.24 1.31 (0.54–3.20) 0.54
Vitamin E 0.81 (0.48–1.38) 0.45 0.91 (0.49–1.70) 0.78 0.89 (0.67–1.18) 0.44 0.92 (0.66–1.28) 0.63
Alpha tocopherol 1.14 (0.56–2.33) 0.70 1.01 (0.38–2.65) 0.98 0.91 (0.60–1.39) 0.68 0.95 (0.57–1.57) 0.85
Thiamin 4.42 (0–76) 0.69 7.86 (0–55) 0.64 2.87 (0.06–118) 0.57 2.74 (0.01–409) 0.69
Riboflavin 0.56 (0–385.93) 0.86 30.44 (0–38) 0.47 0.71 (0.05–10.10) 0.80 1.10 (0.04–30.21) 0.95
Niacin 0.85 (0.61–1.18) 0.33 0.79 (0.52–1.18) 0.25 1.04 (0.89–1.22) 0.56 1.10 (0.89–1.35) 0.37
Vitamin B6 0.06 (0–3.34) 0.17 0.02 (0–3.80) 0.15 1.57 (0.19–12.58) 0.67 1.27 (0.09–16.57) 0.85
Folate total 1.01 (0.96–1.06) 0.59 1.00 (0.94–1.06) 0.95 1.00 (0.98–1.03) 0.50 1.02 (0.99–1.05) 0.12
Folate 0.98 (0.95–1.02) 0.52 0.99 (0.94–1.04) 0.80 0.99 (0.97–1.00) 0.45 0.98 (0.95–1.00) 0.13
Vitamin B12 1.67 (0.63–4.43) 0.29 2.05 (0.57–7.40) 0.27 0.90 (0.64–1.28) 0.58 0.77 (0.51–1.16) 0.21
Biotin 1.11 (0.93–1.31) 0.23 1.16 (0.93–1.44) 0.17 1.05 (0.95–1.15) 0.30 1.03 (0.92–1.15) 0.58
Pantothenic 2.37 (0.22–24.95) 0.47 1.74 (0.07–39.46) 0.72 0.64 (0.25–1.64) 0.36 0.55 (0.17–1.74) 0.31
Vitamin K 1.00 (0.99–1.01) 0.52 1.00 (0.98–1.01) 0.82 0.99 (0.99–1.00) 0.62 0.99 (0.99–1.00) 0.82
Phosphorus 1.00 (1.00–1.00) 0.07 1.00 (1.00–1.00) 0.09 1.00 (1.00–1.00) 0.39 1.00 (1.00–1.00) 0.22
Magnesium 0.98 (0.94–1.03) 0.56 0.97 (0.91–1.04) 0.43 0.99 (0.97–1.01) 0.56 0.99 (0.96–1.01) 0.56
Zinc 1.12 (0.54–2.29) 0.75 1.64 (0.53–5.01) 0.38 0.98 (0.69–1.41) 0.94 1.06 (0.68–1.66) 0.77
Copper 0.73 (0–434.51) 0.92 1.50 (0–45) 0.92 2.64 (0.10–65) 0.55 3.11 (0.06–162) 0.57
Manganese 0.64 (0.09–4.25) 0.64 1.34 (0.09–19.37) 0.83 0.55 (0.23–1.31) 0.18 0.52 (0.17–1.63) 0.26
Selenium 0.99 (0.86–1.14) 0.93 0.93 (0.77–1.12) 0.47 0.99 (0.94–1.03) 0.70 0.96 (0.89–1.02) 0.25
Fluoride 1.00 (1.00–1.00) 0.18 1.00 (0.99–1.00) 0.31 1.00 (1.00–1.00) 0.60 1.00 (1.00–1.00) 0.30
Chromium 0 (0–46) 0.44 0 (0–87) 0.37 97 (0–50) 0.24 88 (0.22–35) 0.06
Total Fibre 1.00 (0.82–1.23) 0.96 1.11 (0.85–1.44) 0.43 1.02 (0.90–1.16) 0.67 0.99 (0.85–1.15) 0.93
Soluble fibre 2.02 (0.59–6.92) 0.25 2.77 (0.49–15.61) 0.24 1.55 (0.66–3.60) 0.30 1.81 (0.61–5.33) 0.28
Insoluble fibre 1.00 (0.99–1.00) 0.84 0.99 (0.99–1.00) 0.71 1.00 (0.99–1.00) 0.72 1.00 (0.99–1.00) 0.77
Crude fibre 0.95 (0.86–1.05) 0.39 0.95 (0.84–1.08) 0.46 1.00 (0.96–1.03) 0.99 0.99 (0.95–1.03) 0.82
Sugar total 1.00 (0.93–1.08) 0.87 0.99 (0.91–1.09) 0.98 0.99 (0.95–1.02) 0.69 0.97 (0.93–1.02) 0.33
Glucose 0.88 (0.75–1.04) 0.15 0.84 (0.68–1.04) 0.11 1.01 (0.92–1.10) 0.68 1.01 (0.91–1.13) 0.77
Galactose 1.00 (0.39–2.54) 0.99 0.70 (0.20–2.46) 0.58 1.10 (0.85–1.42) 0.44 1.202 (0.89–1.61) 0.22
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Note: Model 1: Adjusted for age, breast feeding duration, first menstruation age, post‐menopause age, breast cancer family history, number of pregnancies, smoking, using alcohol drinks and physical activity. Model 2: further adjustments for BMI.

Abbreviations: MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids.

In individuals with the FTO risk allele (AA/AT genotype), the results of logistic regression showed a significant association between BC with dietary intake of omega‐6 fatty acids (OR: 1.31, 95% CI: 1.08–1.60, p: <0.01) after adjusting for confounding factors such as age, breastfeeding duration, first menstruation age, post‐menopause age, breast cancer family history, number of pregnancies, smoking, using alcohol drinks and physical activity (Figure 1). Further adjustment for BMI did not change the results (OR: 1.26, 95%CI: 1.00–1.59, p: 0.04 for PUFA‐6 and OR: 1.00, 95%CI: 1.00–1.00, p: 0.03 for F) (Table 5).

FIGURE 1.

FIGURE 1

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Association between breast cancer and dietary intake of omega‐6 fatty acids in individuals with risk allele (AA/AT) of 9939609 FTO gene polymorphism

4. DISCUSSION

The results of this case–control study indicated that the intake of calories, carbohydrates, omega‐6 fatty acids, iron, thiamine, niacin, folate and maltose was higher in BC patients compared with healthy individuals, while the intake of vitamin D, fluoride, chromium, crude fibre and caffeine in healthy individuals was higher than in patients with BC. The most interesting finding was a significant positive association between dietary intake of omega‐6 fatty acids and BC only in individuals with risk allele of FTO rs9939609 polymorphism. The result on the association between omega‐6 fatty acids and BC was in line with the previous studies that have reported the positive association between omega‐6 fatty acids and BC risk. 32 , 33 , 34 However, Peppone et al. in a multicentre randomized controlled trial reported that omega‐6 fatty acids supplementation significantly decreased pro‐inflammatory markers in the TNF‐α signalling pathway among BC survivors. 35 There is evidence indicating that omega‐6 fatty acids (ω‐6 PUFA) can be involved in pro‐cancer processes. For example, it was reported that ω‐6 PUFA increases the proliferation of the breast carcinoma cell line BT‐474. 36 The pro‐tumour mechanisms of ω‐6 PUFA can be explained by the production of some reactive species, which can act on macromolecules causing DNA damage. In addition, lipids may alter the structure of chromatin and thus affect the accessibility of carcinogens to some specific genes, DNA repair factors and transcription complexes. 37 Moreover, angiogenesis, the key process for tumour growth and metastasis, occurs through the synthesis of omega‐6 fatty acids. 34 Several omega‐6 fatty acids such as prostaglandins, leukotrienes, thromboxanes and hydroxyeicosatraenoic acids promote tumour angiogenesis. These eicosanoids make the tumour microenvironment more favourable for neoplasms and metastasis by encouraging the transcription of angiogenic growth factors, increasing the rate of endothelial cell migration and proliferation, and increasing the rate of vascularization. 38 It has been reported that higher omega‐6 fatty acids intake was associated with increased risk of BC in women. 39 Remarkably, it has been reported that carriers of the A allele of FTO rs9939609 polymorphism had a higher body fat percentage (BF%). 40 Timpson et al. in a cohort study reported that people with the rs9939609 minor allele had a higher intake of fat than those with the TT genotype. 41 Furthermore, we found in previous studies that homozygotes for the rs9939609 risk allele (A) had higher serum leptin compared to the TT genotype. 42 , 43 Also, it has been shown that carriers of the AA genotype of rs9939609 had significantly higher calorie, fat and carbohydrate intake than the carriers of the TT genotype after adjusting for age and sex (p = 0.019, p = 0.010 and p = 0.001, respectively). 44 Moreover, FTO gene polymorphism (AA genotype) influence on gut hormones such as PYY3–36 and acyl‐ghrelin levels that lead to increased food intake especially energy‐dense foods and reduced satiety. 45 , 46 In rs9939609 AA carriers, suppression of acylated ghrelin led to overeating and obesity. 47 In addition, it was indicated that FTO is involved in lipid metabolism through m6‐A‐mediated epigenetic regulation. It has been shown that FTO regulates lipogenesis by altering m6‐A levels of fatty acid synthase (FASN), the key metabolic multi‐subunit enzyme that is responsible for the synthesis of fatty acid. 48 A growing body of evidence suggests that FTO plays critical roles in both overweight/obesity and cancers via m6A demethylase of target genes, which affecting the stability and/or splicing of their mRNAs, in turn leading to promoting adipogenesis, tumorigenesis and drug resistance of cancer cells. The strong association between FTO SNPs or overweight/obesity with an increased risk of cancers suggests that the obesity‐associated function of FTO in metabolism may also contribute to its effects in cancers. 49 Therefore, the higher intake of omega‐6 in individuals with the risk allele of FTO rs9939609 and its positive association with BC risk in those individuals, as shown in the present study, indicates that the association between omega‐6 fatty acids and BC risk can be influenced by FTO rs9939609 polymorphism.

This study enhances our understanding of the interaction between genetic susceptibility and dietary intake on cancer risk through assessing dietary intake, cancer risk and FTO polymorphism. However, we had some limitations in the present study. First, different types of BC including the status of hormone receptors and also the stage of BC were not considered. Second, this study was limited to only one SNP of the FTO gene and other SNPs, and genes may have associations with BC. Finally, the participant sample size was relatively small, and further studies with larger sample sizes are warranted.

5. CONCLUSION

The results of this case–control study showed a significant positive association between BC and dietary intake of omega‐6 fatty acids in individuals with risk allele of FTO rs9939609 polymorphism. These results suggest that the association between BC and dietary intake can be influenced by FTO polymorphism and highlight the interactions of genes and diet on cancer risk. Also, these finding can help strengthen the existing documentation on the need for personalized diets to prevent cancer. Further prospective studies are needed to be carried out on patients with different types of BC to assess the possible effects of the FTO genotype on BC risk.

AUTHOR CONTRIBUTIONS

Saeid Doaei: Supervision (equal). Sepideh Abdollahi: Software (equal). Mohammad Esmail Akbari: Methodology (equal). Saeed Omidi: Investigation (equal); validation (equal). Seyed Mohammad Poorhosseini: Formal analysis (equal). Maryam Gholamalizadeh: Data curation (equal); investigation (equal). Soudeh Ghafouri‐Fard: Methodology (equal). Ghasem Azizi Tabesh: Formal analysis (equal). Alireza Moslem: Visualization (equal). Naeemeh Hasanpour Ardekanizadeh: Software (equal). Seyedeh Elaheh Bagheri: Validation (equal). Azita Hekmatdoost: Validation (equal). Mahdi Alam Rajabi: Visualization (equal). Seyed Alireza Mosavi Jarrahi: Supervision (equal). Mark O. Goodarzi: Validation (equal); writing – review and editing (equal). Golsa Khalatbari Mohseni: Data curation (equal); writing – review and editing (equal).

FUNDING INFORMATION

This study was financially supported by Shahid Beheshti University of Medical Sciences, Tehran, Iran (Code: 74859).

CONFLICT OF INTEREST

The authors declare that they have no competing interests.

Supporting information

Supplementary file 1.

Click here for additional data file. (13.6KB, docx)

ACKNOWLEDGEMENTS

This study was conducted at Cancer Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran. We appreciate all participants and staff in the Cancer Research Center of Shohadaye Tajrish Hospital, Tehran, Iran.

Doaei S, Abdollahi S, Mohseni GK, et al. The effects of FTO gene rs9939609 polymorphism on the association between breast cancer and dietary intake. J Cell Mol Med. 2022;26:5794‐5806. doi: 10.1111/jcmm.17595

DATA AVAILABILITY STATEMENT

Datasets used and/or analysed during the current study are available from the corresponding author on reasonable requests.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary file 1.

Click here for additional data file. (13.6KB, docx)

Data Availability Statement

Datasets used and/or analysed during the current study are available from the corresponding author on reasonable requests.

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