Re: Anomalous observations with regard to prostate cancer research

Letter to the Editor

Anomalous observations with regard to prostate cancer research

Sir,

The article “Anomalous observations with regard to prostate cancer research” [1] was very interesting and informative and I actually agree with all the points raised in that article. Another important observation which may affect the relationship or association between metabolic syndrome (MetS ) and prostate cancer,  is the definition of MetS that is utilized in the various studies. For instance, the WHO definition of MetS uses hyperglycemia or the presence of diabetes mellitus as a mandatory requirement in its definition [2]. If used to define MetS in a study, there would be a very high likelihood of having an inverse relationship between MetS and prostate cancer. This is probably because of the established inverse relationship between diabetes and prostate cancer [3].  On the other hand, if the International Disease Federation (IDF) definition [4], which uses abdominal obesity as a mandatory requirement in its definition of MetS, is used, what would be observed is a more direct proportional relationship between MetS and prostate cancer. This may also be due to the fact that obesity has been associated with increased risk of prostate cancer. In the article by Häggström et al., they actually looked at specific factors of MetS in relation to prostate cancer [5]. They did observe that “hyperglycemia was associated with a decreased risk of prostate cancer while body mass index was associated with increased mortality from prostate cancer”.  Body mass index does correlate positively with measures of central obesity, so if the WHO MetS definition is used to classify their subjects, that inverse relationship comes out but it may not be so if the IDF definition is used. Thank you for your audience.

Dr Iya Eze Bassey

Department of Medical Laboratory Sciences, University of Calabar, Calabar, Nigeria

 

References

1. Hammarsten J. Anomalous observation with regard to prostate cancer in cancer research. BJU Int 2017, 120: 456–457.
2. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications, report of a WHO consultation. Part 1, diagnosis and classification of Diabetes Mellitus. Geneva: WHO publications, 1999.
3. Hsing AW, Sakoda LC, Chua JrSC. Obesity, metabolic syndrome, and prostate cancer. Am J Clin Nutr 2007; 86(3): 843S-857S.
4. Grundy SM, Cleeman JI, Daniels SR et al. American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome, an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005; 112: 2735-2752.
5. Häggström C, Stocks T, Ulmert D et al. Prospective study on metabolic factors and risk of prostate cancer. Cancer 2012; 118: 6199–206.

 

Reply by the author

Thank you, Dr Iya Eze Bassey, for your points of view. You are quite right. This is really quite complex. You raise the difficulties which arise when you are testing the link between metabolic syndrome (MetS) and incident prostate cancer (PC) using the definitions put forth by the World Health Organizations. There are several difficulties here regarding surrogate measures for PC and MetS if your intention is to explore the link between MetS and its aspects and incident PC and PC pathophysiology.

Firstly, there is emerging evidence that the links between MetS and its aspects and incident PC are negative due to bias mechanisms in reports dominated by low-stage incident PC as is the case when the PC diagnoses are the results of PSA-driven diagnostic procedures. By contrast, the link between MetS and its aspects and incident PC are positive in reports dominated by high-stage PC which often is the case in studies based on symptom-driven diagnostic procedures [1,2].

Secondly, over the years, as you have pointed out MetS in man has been defined in different ways by several health organizations [3]. The practical use of the composite definitions of MetS focuses on its potential value as a risk factor for the development of cardiovascular diseases. It has been claimed by the American Diabetes Association and the European Association for the study of Diabetes, however, that MetS is imprecisely defined and appears to be of limited independent value as a marker of risk for cardiovascular diseases [2]. The definitions put forth by World Health Organizations include a mixture of clinical, anthropometric, haemodynamic, endocrine and metabolic aberrations typically observed in individuals with MetS. The four generally accepted definitions used to define MetS have been put forth by the World Health Organization, the National Cholesterol Education Program, the European Group for the Study of Insulin Resistance and the International Diabetes Foundation. None of these can yet be considered the gold standard, however, because they emphasize different aspects of MetS.

Given the limitations of MetS when it comes to cardiovascular diseases and other aspects of MetS, it is reasonable not to use composite definitions of MetS in PC research, if you are interested in the link between MetS and its aspects and incident PC and PC pathophysiology, simply because MetS as defined by World Health Organizations with a mixture of variables represents a poor surrogate measure for the underlying promoting factor(s) for PC growth. In our research, these established definitions of MetS have not been used. Instead, we have focused on risk factor analyses linking established aspects of MetS, such as prevalence of Type 2 Diabetes and treated hypertension, systolic and diastolic blood pressure, body weight, BMI, waist and hip measurements, waist/hip ratio, fasting insulin, HDL-cholesterol, triglycerides and others, which we think are more robust surrogate measures for metabolic aberrations when it comes to exploring the link between MetS and its aspects and incident PC and PC pathophysiology.

 

Dr Jan Hammersten

Gothenburg, Sweden

 

References

1. Hammarsten J. Anomalous observation with regard to prostate cancer in cancer research. BJU Int 2017, 120: 456–457.
2. Hammarsten J, Damber J-E, Haghsheno MA et al. A stage-dependent link between metabolic syndrome and incident prostate cancer. Nature Reviews Urology. In principal accepted for publication.
3. Kahn R, Buse J, Ferannini E et al. The metabolic syndrome: time for critical appraisal. Joint statement from the American Diabetes Association and the European Association for the study of Diabetes. Diabetologia 48, 1684-1699 (2005).