Alcohol consumption and incidence of prostate cancer among Chinese people: A systematic review and meta-analysis

Abstract

Aims: Meta-analyses have suggested a dose-response relationship between level of alcohol use and risk of prostate cancer, but the populations in the included studies are predominantly Caucasian. Many Chinese language studies have not been included in published reviews and/or meta-analyses. The present meta–analysis accessed research reports in both English and Chinese language sources in order to investigate this relationship specifically among Chinese people. Methods: Searches in five large Chinese biomedical bibliographic databases were made for case–control and cohort studies of alcohol consumption and prostate cancer incidence and death (ICD–10: C61) up to May 2017. Studies were coded for design, outcome, drinker and non-drinkers, extent of control for confounding and other study characteristics. Mixed models were used to estimate relative risk (RR) of incidence or death from prostate cancer due to alcohol consumption with study level controls for designs, drinker bias and types of drinkers. Findings: A total of 415 studies were identified of which 25 (20 in Chinese from five Chinese databases and 5 in English from published meta-analyses) satisfied inclusion criteria providing 36 risk estimates of prostate cancer for drinkers versus non-drinkers. There was a total of 36 OR estimates; 27 using patients as controls and 9 using healthy people. Nine studies (14 OR estimates) specified reference abstainers as “never drank” or “no drinking”. Adjusted RR estimates indicated a significantly increased risk of prostate cancer among drinkers (RR=1.46, 95% CI: 1.40 – 1.52, t-test P<0.001) compared to non-drinkers. Dose-response relationships (t-test P<0.001) were evident in three studies that assessed level of alcohol intake. Conclusions: There is a significantly higher risk of prostate cancer incidence among Chinese drinkers than non-drinkers, with some evidence of a dose-response relationship. However, almost all the identified studies suffered from former and/or occasional drinker biases. Few studies had adequate measures of level of alcohol intake and further well-designed studies are required. Prostate cancer is the development of cancer in the prostate, a walnut–sized gland in men that surrounds the top of the urethra and which produces seminal fluid (Bostwick, Crawford, Higano, & Roach, 2004). Its growth and functions are controlled by male hormones such as testosterone. Prostate cancer is the second most common cancer in men worldwide. Around 1.1 million cases were recorded in 2012, accounting for 15% of all new cases of cancer in men (Forman & Ferlay, 2014). It is the fifth most common cause of cancer death in men worldwide. There have been marked geographic, racial and ethnic variations in incidence and mortality of prostate cancer variously due to underdiagnosis, underreporting, differences in screening practices, differences in health-care access, gaps in knowledge and awareness and prevalence level of risk factors such as alcohol consumption (Hsing & Devesa, 2001; Taitt, 2018). It is most commonly diagnosed in high–income western countries, where screening is common. However, the incidence of prostate cancer appears to be increasing in Asian countries such as Japan and China even though prostate‐specific antigen (PSA) testing is not often used (Baade, Youlden, & Krnjacki, 2009). It has been recognized IJADR International Journal of Alcohol and Drug Research The Official Journal of the Kettil Bruun Society for Social and Epidemiological Research on Alcohol 13 Jinhui Zhao and Di Gao et al. –––––– IJADR 8(1) –––––– that prostate cancer is a currently common disease among Chinese males. The incidence rate was about 9.8 per 100,000 males in 2014, a significantly increased trend since 2008 (National Health Commission of the People's Republic of China, 2019; Ye & Zhu, 2015). Therefore, prostate cancer as a chronic disease has become an important public health concern in developing countries such as China. The risk factors for prostate cancer that can be considered established include age, race/ethnicity and family history (Gann, 2002). Many observational studies conducted mainly in Caucasian populations have investigated alcohol consumption as a risk factor for prostate cancer. Conclusions from these studies and of reviews have been conflicting with some finding increased risk of prostate cancer (Hayes et al., 1996; Sesso, Paffenbarger, & Lee, 2001; Watters, Park, Hollenbeck, Schatzkin, & Albanes, 2010), or decreased risk (Dagnelie, Schuurman, Goldbohm, & Van den Brandt, 2004) and others finding no relationship (Hiatt, Armstrong, Klatsky, & Sidney, 1994; Longnecker, 1995; Morton, Griffiths, & Blacklock, 1996; Stemmermann, Nomura, Chyou, & Yoshizawa, 1990; Tavani, Negri, Franceschi, Talamini, & Lavecchia, 1994; Vandergulden, Verbeek, & Kolk, 1994). Over the past few decades there have been several reviews and meta–analyses conducted to examine the association of prostate cancer with alcohol consumption (Bagnardi, Blangiardo, La Vecchia, & Corrao, 2001; Breslow & Weed, 1998; Dagnelie et al., 2004; Dennis, 2000; Fillmore, Chikritzhs, Stockwell, Bostrom, & Pascal, 2009; Li, Yang, & Cao, 2011; Longnecker, 1995; Morton et al., 1996; Rota et al., 2012; Zhao, Stockwell, Roemer, & Chikritzhs, 2016) because of inconsistent results regarding the relationship between prostate cancer and alcohol consumption across individual studies. The most recent one, mainly based on the studies conducted in western countries shows a significant dose-response relationship (Zhao et al., 2016). Because prior reviews and/or meta-analyses were conducted based on the studies searched and analyzed in English journals from English databases, these studies were mainly conducted with Caucasian populations. These published reviews and/or meta-analyses included few studies conducted in non-Caucasian populations such as Asians. Few studies conducted in Asian populations have been published in English journals and thus included in published reviews and meta-analyses. Over years, only six studies conducted on the Chinese population in China were included in published reviews and meta-analyses and one of these six studies was published in a Chinese journal (Breslow & Weed, 1998; Dennis, 2000; Wei, Tang, Yang, Zhan, & Yin, 1994) and other five in English journals (Hsing et al., 1994; Jian, Xie, Lee, & Binns, 2004; Lee et al., 1998; Li et al., 2008; Yang et al., 2006). Meta-analysis by Li et al. (2011) included only four case-control studies of prostate cancer and alcohol consumption and found no relationship (Li et al., 2011). Among these six reviewed studies (nine risk estimates) in Chinese populations living in mainland China, only one shows a significantly increased risk when healthy people were treated as controls (Hsing et al., 1994). No studies were conducted on Chinese populations in other countries or regions. It is unclear whether or not those studies published in Chinese journals or non-English journals that cannot be located in English databases show different results as the risk estimates in published metaanalyses. Biological studies suggested that the effects of alcohol use on incidence of prostate cancer differed by race and/or environment because encoded enzymes involved in metabolizing alcohol differ by race. Alcohol is metabolized in the body mainly by the liver. Most of the ethanol in the body is broken down in the liver by an enzyme called alcohol dehydrogenase (ADH) which transforms ethanol into a toxic compound called acetaldehyde, a known carcinogen (Edenberg, 2007). Acetaldehyde is quickly broken down to a less toxic compound called acetate (Edenberg, 2007) by another enzyme called acetate dehydrogenase (ALDH). Acetate is then broken down to carbon dioxide and water for easy elimination (Edenberg, 2007). A person’s risk of alcohol-related cancers is influenced by their genes that encode enzymes involved in metabolizing alcohol (DruesnePecollo et al., 2009). Many East Asian people carry a version of the gene for ADH that codes for a “superactive” form of the enzyme. This superactive ADH enzyme speeds the conversion of alcohol to toxic acetaldehyde. Among people of Japanese descent, those who have this form of ADH have a higher risk of pancreatic cancer than those with the more common form of ADH (Kanda et al., 2009). Research finds that genes encoding enzymes such as ADH1B involved in alcohol metabolism are polymorphic and that the superactive ADH1B*2 allele is highly prevalent (54-96%) among East Asians (Goedde et al., 1992) but relatively rare among Caucasians (1-23%). The less active ADH1B*1 is a risk factor for alcoholism in both Asians and Caucasians (Zintzaras, 2006; Zintzaras, Stefanidis, Santos, & Vidal, 2006). Some people of East Asian descent carry a variant of the gene for ALDH2 that encodes a defective form of the enzyme. In people who produce the defective enzyme, acetaldehyde builds up when they drink alcohol. The accumulation of acetaldehyde has such unpleasant effects that most people who have inherited the ALDH2 variant are unable to consume large amounts of alcohol and therefore have a low risk of developing alcohol-related cancers such as prostate cancer. Genetic differences in these enzymes suggest that the effect of alcohol consumption on prostate cancer maybe different among Asians such as Chinese from that found among Caucasians and it is thus necessary to investigate the relationship between prostate cancer and alcohol consumption in non-Caucasians, for instance in Chinese populations. There has been a marked increase in the numbers of cancers diagnosed in China between 2000 and 2011 (Chen et al., 2016). Much of this is explained by the aging and growth of the population. Other factors that may have contributed to the increase in the burden of cancer include increases in the prevalence of unhealthy behaviors or cancer‐related lifestyle and improvements in disease awareness, detection services, and data comp