Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk

Cunha, Patricia; Back, Lia Kubelka de Carlos; Sereia, Aline Fernanda Rodrigues; Kubelka, Clara; Ribeiro, M. C. M.; Fernandes, Bráulio Leal; Souza, Ilíada Rainha de

doi:10.1007/s11033-013-2780-3

Cited by 41 publications

(37 citation statements)

References 37 publications

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“…A number of studies have reported associations between FTO or MC4R variants and risk of various types of cancer [10, 11]; some of the associations were independent of obesity, but the mechanisms were unclear [11]. Our results are consistent with the few previous studies that reported null associations of FTO and MC4R with risk of colorectal cancer [3–5].…”

Section: Discussionsupporting

confidence: 90%

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

Yang

Thrift

Figueiredo

et al. 2016

Cancer Epidemiology

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Background Obesity is a convincing risk factor for colorectal cancer. Genetic variants in or near FTO and MC4R are consistently associated with body mass index and other body size measures, but whether they are also associated with colorectal cancer risk is unclear. Methods In the discovery stage, we tested associations of 677 FTO and 323 MC4R single nucleotide polymorphisms (SNPs) 100kb upstream and 300kb downstream from each respective locus with risk of colorectal cancer in data from the Colon Cancer Family Registry (CCFR: 1,960 cases; 1,777 controls). Next, all SNPs that were nominally statistically signif icant (p<0.05) in the discovery stage were included in replication analyses in data from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO: 9,716 cases; 9,844 controls). Results In the discovery stage, 43 FTO variants and 18 MC4R variants were associated with colorectal cancer risk (p<0.05). No SNPs remained statistically significant in the replication analysis after accounting for multiple comparisons. Conclusion We found no evidence that individual variants in or near the obesity-related genes FTO and MC4R are associated with risk of colorectal cancer.

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Section: Discussionsupporting

confidence: 90%

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

Yang

Thrift

Figueiredo

et al. 2016

Cancer Epidemiology

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“…Although there are various studies indicating the relationship between hormonal effects or the obesity gene and its direct effects, the mechanism has not yet been understood clearly (da Cunha et al, 2013). BMI was also found to be a risk factor in this study.…”

Section: Discussionmentioning

confidence: 45%

Family History Attributes and Risk Factors for Breast Cancer in Turkey

Gokdemir-Yazar¹,

Yaprak²,

Colak³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Background: When dealing with breast cancer, early detection is closely associated with determining and closely monitoring high risk groups. The aim of this study was to determine the preventable risk factors that are specific for our country, and to understand which risk factors were most predominant. Materials and Methods: The study was planned as a case-control design. Women diagnosed with breast cancer who visited the Surgery, Obstetrics and Gynaecology, and Radiation Oncology outpatient clinics of the Izmir Dokuz Eylul University (DEU) School of Medicine were accepted as the case group. Then a control group matched for age was established among females who visited the outpatient clinics on the same days. A questionnaire prepared by the researchers was implemented using a face-to-face interview technique. The Mann-Whitney U test was used in the comparisons of the group averages, and the Pearson chi-square test in the comparisons between groups. In order to determine the dominant risk factors, binary logistical regression test was implemented. Results: A total of 138 patients, 69 cases and 69 controls, were included in the study. A significant difference can be detected between the groups in terms of BMI, smoking, breast cancer prevalence among first degree family members, presence of breast cancer among distant family members, existence of other types of cancers among family members and the age of onset of menopause (p<0.05). Logistical regression analysis revealed that the presence of breast cancer among first degree relatives increased the risk of developing breast cancer 5.7 times. Conclusions: Although some results of this study are compatible with findings in the literature, some are not. In order to determine unique risk factors, there is a clear need for large-scale studies.

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“…This variant has been associated with BMI, but the relation with etiological pathways for ER-negative breast cancer is unknown. However, when analyzing SNPs in 67 breast cancer susceptibility loci, Long et al [38] Finally, in a Brazilian population it was found that when FTO SNPs rs1121980 and rs9939609 were analyzed in combination with the presence of SNP rs17782313 in the melanocortin-4 receptor (MC4R), a 4.9-fold higher risk of developing breast cancer was observed [43]. Recently, Iles et al [44] found that other FTO SNPs present in an intron (e.g., intron 8) not associated with obesity may be associated with the risk of developing cancer (Table 1 summarizes all FTO SNPs positively associated with some type of cancer).…”

Section: Fto Polymorphisms and Cancermentioning

confidence: 99%

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview

Hernández-Caballero

Sierra-Ramírez

2014

Mol Biol Rep

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The FTO (fat mass and obesity-associated) gene has a strong linkage disequilibrium block, within which SNPs have been identified that are involved in the development of obesity. Recently some of these variants have also been associated with cancer. However, identification of the possible mechanisms that could explain these associations has proven to be elusive. It has been found that FTO polymorphisms can regulate the expression of genes at large kilobases of distance as well as the expression of the FTO gene itself, and regions for transcription factor binding. To date it has been observed that variants rs9939609, rs17817449, rs8050136, rs1477196, rs6499640, rs16953002, rs11075995 and rs1121980 are associated with the risk of developing cancer. Some studies have produced negative results when comparing the same polymorphisms, but make a simple association between polymorphic variants and cancer, have proved difficult because this relation is by nature multifactorial. A certain degree of variation resulting from the improper design of studies or processing of data can lead to erroneous conclusions. However, it is now unquestionable that certain FTO polymorphisms regulate genetic expression related to cancer susceptibility, although this field is just beginning to be understood.

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Interaction between obesity-related genes, FTO and MC4R, associated to an increase of breast cancer risk

Cited by 41 publications

References 37 publications

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

Common variants in the obesity-associated genes FTO and MC4R are not associated with risk of colorectal cancer

Family History Attributes and Risk Factors for Breast Cancer in Turkey

Single nucleotide polymorphisms of the FTO gene and cancer risk: an overview

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