Katherine McGlynn

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NCI, DCEG, HREB

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PLCO (Learn more about this study)

2014-0187

Sep 3, 2014

Endogenous Hormone Levels and Risk of Liver Cancer

Incidence and mortality rates of liver cancer have been increasing in the United States (U.S.) for over 30 years. One intriguing characteristic of liver cancer is the male predominance, with a male:female ratio of 2.8:1 in the U.S. [1]. While this may be partially explained by a higher prevalence of known risk factors among men (e.g., hepatitis B and C virus [HBV/HCV] or alcohol consumption), these factors do not fully explain the sex differences in liver cancer incidence [2, 3]. One hypothesis is that hormones could be responsible for the sex disparity [4]. In animal models, estrogen or castration reduces liver cancer development in male rodents, while testosterone or ovariectomy increases liver cancer development in female rodents [3]. Similarly, in the Liver Cancer Pooling Project (LCPP), an increased risk of liver cancer was seen among women who had an oophorectomy (McGlynn et al., submitted). Additionally, several nested case-control study have found increased serum testosterone levels in liver cancer patients compared to controls [5-8], and a nested case-control study in the European Prospective Investigation into Cancer also found higher levels of sex hormone binding globin increased risk of liver cancer [9].

In order to study the etiology of liver cancer using a prospective design, the Liver Cancer Pooling Project (LCPP), a pooling project within the NCI Cohort Consortium, was initiated in 2009. Fourteen U.S. based cohorts are contributing questionnaire data and serum samples to the LCPP. Questionnaire data from PLCO participants, as well as serum for HBV/HCV determinations, have already been approved for this consortia effort. While known risk factors, such as HBV/HCV and alcohol consumption, have been studied extensively, an examination of other putative factors, such as hormones, might greatly enhance the current understanding of the etiology of liver cancer in the U.S.