Elsevier

Environment International

Volume 63, February 2014, Pages 35-39
Environment International

Case–control study on perfluorinated alkyl acids (PFAAs) and the risk of prostate cancer

https://doi.org/10.1016/j.envint.2013.10.005Get rights and content

Highlights

  • Perfluorinated alkyl acids were analyzed in cases with prostate cancer and controls.

  • Heredity was a risk factor for prostate cancer.

  • The analyzed PFAAs gave increased risk in cases with heredity for prostate cancer.

Abstract

Perfluorinated alkyl acids (PFAAs) are emerging environmental contaminants. Possible health effects for humans include increased risk for cancer but the knowledge is limited. In this study serum concentrations of certain perfluorinated sulfonates (PFHxS and PFOS) and carboxylates (PFOA, PFNA, PFDA, PFUnDA) were analyzed among 201 cases with prostate cancer and 186 population based control subjects. All blood samples were collected during 2007–2011 and no case had been treated with radio- or chemotherapy before enrolment in the study. The blood concentrations did not differ statistically significant between cases and controls except for PFDA with higher concentration among the cases (p = 0.03). Analyses based on Gleason score and prostate specific antigen (PSA) level did not change the results. Heredity was a risk factor for prostate cancer yielding odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.01–3.1. The analyzed PFAAs yielded statistically significant higher ORs in cases with a first degree relative reporting prostate cancer, e.g., PFOA gave OR = 2.6, 95% CI = 1.2–6.0 and PFOS gave OR = 2.7, 95% CI = 1.04–6.8. The results showed a higher risk for prostate cancer in cases with heredity as a risk factor. In further studies interaction between gene and environment should be considered.

Introduction

Perfluoroalkyl substances (PFASs) are a group of chemicals consisting of a fluorinated carbon chain with at least one additional atom or functional group. If the functional group is an acid such as carboxylate group or sulfonate group it is part of the subgroup perfluoroalkyl acids (PFAAs). The most studied PFAAs are perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA).

PFASs are stable in air at high temperatures, non-flammable and not readily degraded (Lau et al., 2007). The stability makes them practically non-biodegradable and persistent in the environment (Key et al., 1997, Key et al., 1998, Prescher et al., 1985). They are used in many industries and consumer products including for example water-resistant coating for textiles, oil-resistant coatings for paper products approved for food contact, electroplating, fire-fighting foams, paints, waxes and polishes (Lau et al., 2007) because of their ideal surfactant properties (Kissa, 2001).

Perfluorooctanesulfonyl-fluoride (PFOSF) works as a building block for many fluorochemicals, and can degrade to PFOS. In 1949 3M started their production of PFOSF-based chemicals (3M Company, 1999). Besides 3M's largest production sites in the US and Belgium, there were also production in other European countries, Asia, and South America (Paul et al., 2009). The total global production of PFOSF products from the start until 2002 has been estimated to 96,000 tons, with a further 26,500 tons of mainly solid unwanted by-products or wastes (Paul et al., 2009). In 2000 3M voluntarily started to phase-out their production of PFOS, and the global production dropped from 3500 tons in 2000 to 175 tons by 2001 (3M Company, 2003). PFOS, which was added to the Stockholm convention on persistent organic pollutants (POPs) in 2009 (http://chm.pops.int/Convention/ThePOPs/tabid/673/language/en-US/Default.aspx), is still in production in Asia (Carloni, 2009, UNEP, 2012). Homologues with various carbon chain lengths and precursor compounds that potentially can degrade to persistent PFASs are still produced and used in consumer products (Buck et al., 2011).

In 2001 a global distribution of PFOS in wildlife was reported (Giesy and Kannan, 2001). The highest concentrations of PFAAs have been found in the livers of fish-eating animals living near more industrialized areas (Lau et al., 2007). PFAAs have also been reported in the environment including surface seawaters, coastal waters, river waters, fresh water, drinking water, rainwater from an urban center, air, sludge, soils, sediments and ice caps (Lau et al., 2007, Saito et al., 2004, So et al., 2004). PFAAs have also been found in human samples taken worldwide, and the analytes most often detected were PFOS, PFOA and perfluorohexane sulfonate (PFHxS) (Lau et al., 2007). Declining levels of PFOS and PFOA in blood samples have been seen in the US and Norway after the 3M phase-out (Haug et al., 2009, Olsen et al., 2007a).

The largest part of the chronic exposure to PFOS and PFOA, except from occupational exposure, is likely to come from the diet (Fromme et al., 2009, Trudel et al., 2008) and a minor route from consumer products (Trudel et al., 2008). Danish men (n = 652) that have never smoked had higher levels of PFOS and PFOA than current smokers and BMI and alcohol were inversely associated with both compounds (Eriksen et al., 2011).

Pharmacokinetic studies have shown that PFOS and PFOA are mainly distributed to the blood, kidney and liver (Hundley et al., 2006, Johnson et al., 1979, Seacat et al., 2002, Seacat et al., 2003). The half-lives of serum elimination of PFOS and PFOA in humans have been reported to be around 5 years and 4 years, respectively (Olsen et al., 2007b).

A statistically significant 3.3-fold increase in prostate cancer mortality among employees with exposed jobs and over ten years of employment was found in a cohort study of 3537 workers at a PFOA production plant. However, there were only six prostate cancer deaths overall (Gilliland and Mandel, 1993). In a retrospective cohort study with 2083 members working in a PFOS based fluorochemical production facility an increased risk for bladder cancer mortality was found (Alexander et al., 2003). In a follow-up on bladder cancer mortality the increased standardized mortality ratio was confirmed, but it was not statistically significant (Alexander and Olsen, 2007). Regarding other malignant diseases, including prostate cancer, and benign disorders and adverse pregnancy outcomes there were no significant associations with PFOS-exposed jobs (Grice et al., 2007).

In a cohort of all individuals who ever worked at the DuPont Washington Works polymer production plant at any time between plant start-up on January 1, 1948, and December 31, 2002 no statistically significant elevation of standardized mortality ratio (SMR) was observed for prostate cancer. However, the cohort consisted of only 12 cases of mortality due to prostate cancer and no estimation of exposure was made (Leonard et al., 2008).

No association with liver, pancreatic or testicular cancer, or with cirrhosis of the liver was seen in a mortality study of a cohort of 3993 employees at an ammonium perfluorooctanoate (APFO) manufacturing facility. APFO dissociates to PFOA in blood. However, in the groups with moderate or high exposure to APFO an increased risk for prostate cancer and cerebrovascular disease was found (Lundin et al., 2009).

The risk of prostate, bladder, pancreatic and liver cancer and exposure to PFAAs in non-occupational groups was investigated in a prospective Danish cohort. A 30–40% increase in risk estimates for prostate cancer was observed for the three upper quartiles of PFOS concentration compared with the lowest quartile (Eriksen et al., 2009). Levels of POPs and PFAAs were measured in 31 breast cancer cases and 115 controls during 2000–2003 in Greenland with a statistically significant increased risk in relation to the level of serum PFOS and sum of PFSA and total sum of POPs plus PFAAs (Bonefeld-Jorgensen et al., 2011).

Prostate cancer is the most common cancer type among men in Sweden. In 2011 in total 9663 cases were registered which is 32.2% of all cancer among men (Socialstyrelsen, 2012).

Risk factors for prostate cancer are numerous and heterogeneous. They include genetic, inflammatory and infectious, androgen-related, dietary, age-related, and ethnic factors that contribute to prostate cancer susceptibility (Patel and Klein, 2009).

The aim of this study was to investigate if there is an association between prostate cancer and levels of certain PFAAs in blood. The regional ethics committee approved the study.

Section snippets

Study design

Patients with prostate cancer who were admitted during 2007–2011 to the Department of Oncology at the University Hospital in Örebro to receive treatment with radiation or chemotherapy were asked to participate in the study before the treatment. In total 252 consecutive patients with newly diagnosed prostate cancer were invited. Of these 25 did not want to participate, 25 never answered the postal inquiry and 2 cases never gave blood in spite of initially willing to participate. The sample

Overall results

The results were based on 201 cases (median age 67 years, range 49–79) and 186 controls (median age 67 years, range 50–79). The median BMI was 26.8 kg/m2 for cases and 26.4 kg/m2 for controls. For PFDA and PFUnDA the result was missing for some cases and controls as listed in Table 1, which did not met the QA/QC criteria due to interferences or low recovery.

Table 1 displays overall results of PFAA concentrations. For PFDA statistically significant higher concentrations were found in the cases

Discussion

The main finding of this study was an association between certain PFAAs and hereditary prostate cancer. Heredity for prostate cancer as such gave a statistically significant higher risk for the disease as would be expected (Patel and Klein, 2009). We analyzed the different PFAAs in relation to heredity and found higher OR for the analyzed chemicals for cases with hereditary risk, see Table 4. A statistically significant interaction was seen for PFHxS. PFAAs without heredity did not

Conclusion

As discussed in the introduction some previous studies have indicated an association between certain PFAAs and prostate cancer, although the results are not consistent. In this study a higher risk was found in the case group with hereditary prostate cancer. Clearly our results show an interaction between gene and environment. The possible mechanism is unknown. We found no association with clinical stage of the disease. Interestingly these results may cast further light on the etiology of

Acknowledgment

Ms Iréne Larsson is acknowledged for assistance in the data collection. Helén Björnfoth and Ulrika Eriksson are acknowledged for laboratory work. Valuable clinical comments by Dr Bengt Johansson are acknowledged.

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