Increased Adiposity May Be Protective for Breast and Prostate Cancer in Certain Patients

Increased adiposity was shown to be causally protective for breast and prostate cancer, according to the results of a new study presented at the American Society of Human Genetics 2020 Virtual Meeting.¹

The investigators suggested that the protective effects observed in prostate cancer may, at least in part, be due to safe sequestration of harmful chemicals in adipose cells. However, further research will still be required to provide sufficient evidence of these findings.

“It’s first necessary to figure out the mechanisms through which obesity may protect against or be a risk factor for cancer,” Hasnat Amin, BSc, a doctoral student at Brunel University London, said in a press release.² “The next step would be to use these mechanisms to maximize the protective effect of obesity on breast and prostate cancer risk without the often-reported negative effects of increased weight on cardiometabolic health.”

In this study, investigators used 1-sample Mendelian randomization to assess the causal effect of adiposity measures, including body mass index (BMI), body fat percentage, waist circumference, hip circumference, and waist-to-hip ratio, on breast and prostate cancer risk in the UK Biobank (UKB); the prospective cohort study included over 500,000 participants. The study findings were then replicated by 2-sample Mendelian randomization using data from the Breast Cancer Association Consortium, or BCAC, which included 122,977 cases of breast cancer and 105,974 controls, and the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome, or PRACTICAL, Consortium, which included 79,194 cases of prostate cancer and 61,112 controls.

The investigators revealed that women who were genetically predisposed to being heavier developed breast cancer at lower rates than those who were not. These data suggest that the higher risks of breast cancer typically associated with increased weight may be due to other factors.

Further, heavier men were found to be less likely to develop prostate cancer compared with those who weighed less, both observationally and when using genetically predicted measures. Importantly, this correlation was significantly greater in men who were exposed to carcinogenic substances at work, since fat cells likely play a role in absorbing and safely storing harmful chemicals.

Although these collective findings demonstrate that genetic predisposition to increased weight is protective against breast and prostate cancer, Amin indicated that further research is necessary to determine how this is realized, especially in breast cancer.

It is important to note that Amin and his colleagues are not suggesting that maintaining increased body weight is a cancer prevention strategy. Instead, he explained that public health messages should target the negative consequences of obesity while also considering the positive aspects.

“Public health campaigns frequently describe obesity as being a causal risk factor for cancer and, therefore, portray weight loss as an effective cancer prevention strategy,” said Amin. “However, our findings contradict this idea.”

“Furthermore, there may even be certain risks in advising fat loss if, for example, fat cells are involved in the absorption of carcinogenic substances.”

References:

1. Amin H, Kaewsri P, Yiorkas AM, Cook H, Drenos F, Blakemore A. Increased adiposity is protective for breast and prostate cancer: A Mendelian randomisation study using up to 132,413 breast cancer cases and 85,907 prostate cancer cases. Presented at: American Society of Human Genetics 2020 Virtual Meeting; October 27-30, 2020; Virtual. Abstract 2359.

2. Genetic Predisposition to Increased Weight is Protective for Breast and Prostate Cancer. News release. ASHG News. Published October 26, 2020. Accessed December 4, 2020. https://www.ashg.org/publications-news/press-releases/genetic-predisposition-increased-weight-protective-breast-prostate-cancer/