Energy homeostasis genes and survival after breast cancer diagnosis: the Breast Cancer Health Disparities Study

Abstract

Purpose The leptin-signaling pathway and other genes involved with energy homeostasis (EH), have been examined in relation to breast cancer risk as well as to obesity. We test the hypothesis that genetic variation in EH genes influences survival after diagnosis with breast cancer and that body mass index (BMI) will modify that risk. Methods We evaluated associations between 10 energy homeostasis genes and survival among 1186 non-Hispanic white (NHW) and 1155 Hispanic/Native American women diagnosed with breast cancer. Percent Native American (NA) ancestry was determined from 104 Ancestry Informative Markers. Adaptive rank truncation product (ARTP) was used to determine gene and pathway significance. Results The overall EH pathway was marginally significant for all-cause mortality among women with low NA ancestry (PARTP = 0.057). Within the pathway, ghrelin (GHRL) and leptin receptor (LEPR) were significantly associated with all-cause mortality (PARTP = 0.035 and 0.007, respectively). The EH pathway was significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.038). Three genes, cholecystokinin (CCK), GHRL, and LEPR were significantly associated with breast cancer-specific mortality among women with low NA ancestry (PARTP = 0.046, 0.015, and 0.046, respectively) while neuropeptide Y (NPY) was significantly associated with breast cancer-specific mortality among women with higher NA ancestry (PARTP = 0.038). BMI did not modify these associations. Conclusions Our data support our hypothesis that certain EH genes influence survival after diagnosis with breast cancer; associations appear to be most important among women with low NA ancestry.

Genetic Epidemiology of Breast Cancer in Latin America

“…Different analyses conducted in the Breast Cancer Health Disparities Study samples analyzed tag SNPs in genes related to inflammation and energy balance, taking into account possible interactions with body mass index [ 159 , 160 , 161 , 162 , 163 , 164 ]. Few Latin American studies tested the association between genes in inflammation and energy balance pathways and breast cancer risk ( TNF-α , RETN , CAP1 , and PTGS2 genes).…”

Attribution of Ghrelin to Cancer; Attempts to Unravel an Apparent Controversy

“…Polymorphism of GHRL gene was linked to both all-cause and breast cancer-specific mortalities. GHRL rs27647-GG genotype was correlated with worse all-cause mortality, whereas GHRL rs3755777-C allele conferred overall survival advantage (102). Future studies can explore if these polymorphisms alter expression of ghrelin peptide and receptors.…”

Literature review of data-based models for identification of factors associated with racial disparities in breast cancer mortality

“…Two SNPs in the IL23R gene were significantly associated with breast cancer-specific mortality among women with lower Native American ancestry (Slattery et al, 2014a). From the 17 publications of the Breast Cancer Disparities Study included in this review (Boone et al, 2014a(Boone et al, , 2015Connor et al, 2013Connor et al, , 2014Connor et al, , 2016aConnor et al, , 2016bPellatt et al, 2013Pellatt et al, , 2016Slattery et al, 2013aSlattery et al, , 2013bSlattery et al, , 2013cSlattery et al, , 2014aSlattery et al, , 2014bSlattery et al, , 2014cSlattery et al, , 2014dSlattery et al, , 2015aSlattery et al, , 2015b, 10 found genetic variations in cellular proteins that were specifically associated with breast cancer mortality by racial genetic ancestry (Connor et al, 2013;Pellatt et al, 2013Pellatt et al, , 2016Slattery et al, 2013aSlattery et al, , 2013bSlattery et al, , 2013cSlattery et al, , 2014aSlattery et al, , 2014bSlattery et al, , 2014cSlattery et al, , 2014d thus providing evidence of the significant differences in breast cancer development per genetic ancestry. Such analyses are yet to be replicated in patients with racial backgrounds different from AA and Hispanic/Native American.…”

“…For example, to compare the isolated effect of race in survival, a Kaplan-Meier curve can be fitted for each race group, and statistical differences between race groups can be obtained through the Log-rank test (Aggarwal et al, 2015). Single degree Wald tests were generally used to tests linear interactions between two factors (Pellatt et al, 2016). Adaptive Rank Truncated Products were always used to determine joint associations between genetic abnormalities and mortality (Slattery et al, 2014a).…”