In the first prospective study of directly measured body fat distribution and prostate cancer risk, investigators found that higher levels of abdominal and thigh fat are associated with an increased risk of aggressive prostate cancer.
Published early online in Cancer, a peer-reviewed journal of the American Cancer Society, the findings may lead to a better understanding of the relationship between obesity and prostate cancer and provide new insights for treatment.
Previous studies have shown that obesity is associated with an elevated risk of advanced prostate cancer and a poorer prognosis after diagnosis.
Also, emerging evidence suggests that the specific distribution of fat in the body may be an important factor.
To provide high quality evidence, Barbra Dickerman, Ph.D., of the Harvard T.H. Chan School of Public Health, and her colleagues analyzed body fat distribution using the gold-standard measure of computed tomography imaging and assessed the risk of being diagnosed with, and dying from, prostate cancer among 1,832 Icelandic men who were followed for up to 13 years.
During the study, 172 men developed prostate cancer and 31 died from the disease.
The accumulation of fat in specific areas – such as visceral fat (deep in the abdomen, surrounding the organs) and thigh subcutaneous fat (just beneath the skin) – was associated with the risk of advanced and fatal prostate cancer.
High body mass index (BMI) and high waist circumference were also associated with higher risks of advanced and fatal prostate cancer.
“Interestingly, when we looked separately at men with a high BMI versus low BMI, we found that the association between visceral fat and advanced and fatal prostate cancer was stronger among men with a lower BMI.
Prostate cancer (PCa) is the most common male cancer in western countries with more than one million men diagnosed with prostate cancer in 2012 worldwide .
In France, more than 50,000 prostate cancer cases were diagnosed in 2011, with almost 9,000 deaths which represents the third cause of cancer-related mortality [2, 3].
Except age, ethnic origin, and family history of prostate cancer that are well-established non modifiable risk factors, the etiology of prostate cancer remains largely unknown.
Obesity has been associated with an increased risk of several cancers, including breast in post-menopausal women, endometrium, kidney, colon, and pancreas [4, 5].
However, the link between obesity and prostate cancer is still under debate, with inconsistent results across studies and according to the indicators used to characterize obesity.
An extensive literature, almost 80 studies, has focused on body mass index (BMI), and null or weak results have been reported, as showed in several meta-analyses [5–9].
Nevertheless, out of the five meta-analyses published on BMI and prostate cancer, only two, which represents less than 25 studies overall [7, 8], were able to distinguish the aggressiveness of prostate cancer showing positive associations between BMI and aggressive prostate cancer.
The lack of epidemiological evidence between BMI and prostate cancer is questionable, while some positive associations have been reported with other anthropometric indicators, such as waist circumference (WC) or waist-hip ratio (WHR) [10–19].
Therefore, it has been hypothesized that BMI itself is not the adequate indicator to capture obesity as it is influenced by both adipose and non-adipose tissue and does not take into account adipose distribution (i.e. abdominal or peripheral adiposity).
It is more likely that abdominal obesity indicators (i.e. WC and WHR) independently, or combined with BMI, would better capture the concept of body fat distribution .
Several biological mechanisms have been proposed to understand how obesity may be related to prostate cancer. First, obesity may be correlated with a low physical activity level, suspected to increase the risk of prostate cancer .
Second, obese men have higher levels of insulin and insulin-like growth factor [21, 22], thought to promote carcinogenesis and inhibit apoptosis [23–25].
Finally, experimental and epidemiological studies also suggested that chronic inflammation may be associated either with initiation or progression of several cancers, including prostate cancer [26–31].
Indeed it has been suggested that obesity confers a low-grade inflammation status that may contribute to cancer development.
In that context, we aimed to identify modifiable risk factors exploring associations between several anthropometric indicators and prostate cancer, using data from the Epidemiological study of Prostate Cancer (EPICAP).
The precision of these estimates was limited in this subgroup analysis, but this is an intriguing signal for future research,” Dickerman noted.
Additional studies are needed to investigate the role of fat distribution in the development and progression of prostate cancer and how changes in fat stores over time may affect patients’ health.
“Ultimately, identifying the patterns of fat distribution that are associated with the highest risk of clinically significant prostate cancer may help to elucidate the mechanisms linking obesity with aggressive disease and target men for intervention strategies,” said Dickerman.
An accompanying editorial notes that lifestyle interventions – such as diet and exercise – that target fat loss may also reduce the risk of prostate cancer.
More information: “Body fat distribution on CT imaging and prostate cancer risk and mortality in the AGES-Reykjavik Study.” Cancer (2019). doi.wiley.com/10.1002/cncr.32167
“Obesity, visceral and prostate cancer: What is the role of lifestyle interventions?” Cancer (2019). doi.wiley.com/10.1002/cncr.32165
Journal information: Cancer
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