Variation in Genes Related to Obesity, Weight, and Weight Change and Risk of Contralateral Breast Cancer in the WECARE Study Population

Abstract

Background Body mass index (BMI), a known breast cancer risk factor, could influence breast risk through mechanistic pathways related to sex hormones, insulin resistance, chronic inflammation and altered levels of adipose derived hormones. Results from studies of the relationship between BMI and second primary breast cancer have been mixed. To explore the relationship between BMI and asynchronous contralateral breast cancer (CBC), we examined whether variants in genes related to obesity, weight and weight change are associated with CBC risk. Methods Variants in twenty genes (182 single nucleotide polymorphisms) involved in adipose tissue metabolism, energy balance, insulin resistance and inflammation, as well as those identified through genome-wide association studies of BMI and type II diabetes were evaluated. We examined the association between variants in these genes and the risk of CBC among Caucasian participants (643 cases with CBC and 1,271 controls with unilateral breast cancer) in the population-based Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study using conditional logistic regression. Results After adjustment for multiple comparisons, no statistically significant associations between any variant and CBC risk were seen. Stratification by menopausal or estrogen receptor status did not alter these findings. Conclusion Among women with early onset disease who survive a first breast cancer diagnosis there was no association between variation in obesity-related genes and risk of CBC. Impact Genetic variants in genes related to obesity are not likely to strongly influence subsequent risk of developing a second primary breast cancer.

Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study

“…Leptin can activate POMC and inhibit NPY [38] and is involved in inflammatory response and regulation of insulin sensitivity. While we did not observe associations between LEP SNPs and breast cancer risk, similar to reports by others [8,10,39], we did observe several associations between LEPR and breast cancer risk. The biological effects of LEP are exerted through binding to the leptin receptor.…”

“…Both adiponectin and leptin are adipokines that are secreted by adipocytes [7]. Leptin has been directly associated with obesity, while adiponectin has been inversely associated with obesity and visceral fat accumulation [8]. Among these genes, LEP and LEPR have been studied the most with breast cancer and have been associated with obesity [9].…”

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

“…Despite the fact that Kaklamani et al [39] reported a significant association between FTO rs1477196 and breast cancer risk in predominantly Caucasian patients, Kusinska et al [40] found no such relation with the FTO variants rs993909 and rs9930506 in a sample of 134 Polish women. The same negative result was obtained by Brooks et al when they tried to find a relationship between FTO variants associated with BMI and the subsequent risk of second primary breast cancer [41]. This is probably because the mechanisms for the development of metastasis do not involve the same risk factors as first tumor emergence.…”

The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants

“…Previous studies have suggested that cancer risk factors include an unhealthy life style, environmental pollution, radiation, infection, and immunity dysfunction 45 46 47 . Additionally, studies have increasingly focused on genetic factors 48 49 50 . In recent years, numerous studies reported an association between the SDF-1 rs1801157 polymorphism and cancer susceptibility, but the results were inconsistent or inconclusive.…”