Synergistic Effects of Genetic Variants of Glucose Homeostasis and Lifelong Exposures to Cigarette Smoking, Female Hormones, and Dietary Fat Intake on Primary Colorectal Cancer Development in African and Hispanic/Latino American Women

被引：1

作者：

Jung, Su Yon ^{[1
]}

Sobel, Eric M. ^{[2
,3
]}

Pellegrini, Matteo ^{[4
]}

Yu, Herbert ^{[5
]}

Papp, Jeanette C. ^{[2
]}

机构：

[1] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Translat Sci Sect, Sch Nursing, Los Angeles, CA 90024 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Computat Med, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Life Sci Div, Los Angeles, CA USA

[5] Univ Hawaii, Canc Ctr, Canc Epidemiol Program, Honolulu, HI USA

来源：

FRONTIERS IN ONCOLOGY | 2021年 / 11卷

基金：

美国国家卫生研究院;

关键词：

glucose homeostasis; random survival forest; attributable risk; smoking; endogenous estrogen; polyunsaturated fatty acid; colorectal cancer; African and Hispanic; Latino American women; I IGF-I; INSULIN-RESISTANCE; GROWTH-FACTOR; PATHWAY ANALYSIS; GLYCEMIC TRAITS; RANDOM FORESTS; COLON-CANCER; RISK; OBESITY; POLYMORPHISMS;

D O I：

10.3389/fonc.2021.760243

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Disparities in cancer genomic science exist among racial/ethnic minorities. Particularly, African American (AA) and Hispanic/Latino American (HA) women, the 2 largest minorities, are underrepresented in genetic/genome-wide studies for cancers and their risk factors. We conducted on AA and HA postmenopausal women a genomic study for insulin resistance (IR), the main biologic mechanism underlying colorectal cancer (CRC) carcinogenesis owing to obesity. Methods With 780 genome-wide IR-specific single-nucleotide polymorphisms (SNPs) among 4,692 AA and 1,986 HA women, we constructed a CRC-risk prediction model. Along with these SNPs, we incorporated CRC-associated lifestyles in the model of each group and detected the topmost influential genetic and lifestyle factors. Further, we estimated the attributable risk of the topmost risk factors shared by the groups to explore potential factors that differentiate CRC risk between these groups. Results In both groups, we detected IR-SNPs in PCSK1 (in AA) and IFT172, GCKR, and NRBP1 (in HA) and risk lifestyles, including long lifetime exposures to cigarette smoking and endogenous female hormones and daily intake of polyunsaturated fatty acids (PFA), as the topmost predictive variables for CRC risk. Combinations of those top genetic- and lifestyle-markers synergistically increased CRC risk. Of those risk factors, dietary PFA intake and long lifetime exposure to female hormones may play a key role in mediating racial disparity of CRC incidence between AA and HA women. Conclusions Our results may improve CRC risk prediction performance in those medically/scientifically underrepresented groups and lead to the development of genetically informed interventions for cancer prevention and therapeutic effort, thus contributing to reduced cancer disparities in those minority subpopulations.

引用

页数：13