Cancer risk among residents of Rhineland-Palatinate winegrowing ...

Journal of Occupational Medicine and Toxicology

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Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study Andreas Seidler1,2,4, Gaël Paul Hammer*2,4, Gabriele Husmann4, Jochem König2, Anne Krtschil3, Irene Schmidtmann2 and Maria Blettner2 Address: 1Federal Institute for Occupational Safety and Health (BAuA), Berlin, Germany, 2Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), Johannes Gutenberg-University Mainz, Germany, 3Cancer Registry of Rhineland-Palatinate, Notification Office, Mainz, Germany and 4Cancer Registry of Rhineland-Palatinate, Registration Office, Mainz, Germany Email: Andreas Seidler - [email protected]; Gaël Paul Hammer* - [email protected]; Gabriele Husmann - [email protected]; Jochem König - [email protected]; Anne Krtschil - [email protected]; Irene Schmidtmann - [email protected]; Maria Blettner - [email protected] * Corresponding author

Published: 6 June 2008 Journal of Occupational Medicine and Toxicology 2008, 3:12

doi:10.1186/1745-6673-3-12

Received: 30 January 2008 Accepted: 6 June 2008

This article is available from: http://www.occup-med.com/content/3/1/12 © 2008 Seidler et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Aim: To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study. Methods: On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as reference. Results: A statistically significant positive association with the extent of viniculture can be observed for non-melanoma skin cancer in both males and females, and additionally for prostate cancer, bladder cancer, and non-Hodgkin lymphoma in males, but not in females. Lung cancer risk is significantly reduced in communities with a large area under cultivation. In the side-analysis, elevated SIR for endocrine-related tumors of the breast, testis, prostate, and endometrium were observed. Conclusion: This study points to a potentially increased risk of skin cancer, bladder cancer, and endocrine-mediated tumors in Rhineland-Palatinate winegrowing communities. However, due to the explorative ecologic study design and the problem of multiple testing, these findings are not conclusve for a causal relationship.

Introduction Some previous studies point to a potential association between pesticide exposure resp. farming or winegrowing and lymphoma [1-5] or multiple myeloma [6-11], brain

cancer [12-14], prostate cancer [15], or bladder cancer [16,17]. However, the mechanisms of the suspected carcinogenic effects of pesticides are widely unclear.

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Journal of Occupational Medicine and Toxicology 2008, 3:12

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Among the hypothesis on potential carcinogenic mechanisms from pesticides, the endocrine mediated effects have received much attention. Several pesticides interact with endocrine receptors in vitro or have endocrine-mediated effects in laboratory animals in vivo: The European Union has listed over 40 pesticides suspected to interfere with the hormone system of humans and wildlife [18]. As endocrine-related mechanisms play an etiologic role in several cancers in humans, the potential association between exposure to pesticides with endocrine activity and cancer incidence has been discussed in the last years. Many epidemiological studies have, for example, examined the relationship between pesticides and breast cancer [19]. However, although endogenous and exogenous estrogens are known to play a causal role in the aetiology of breast cancer, the to date epidemiological and experimental evidence is not conclusive for an association between exposure to organochlorine pesticides and breast cancer incidence (for an overview, see [19]). According to Barlow [19], the evidence on other endocrine-related tumour sites (testes, prostate, endometrium) is too sparse to draw any conclusions concerning pesticides.

was categorized according to the proportion of area under wine cultivation of the whole community area (small: >0 to 5 percent; medium: >5 to 20 percent; large: >20 percent area under wine cultivation; see Table 1) based on official data for 1996. 1.3 percent of the total area of communities with a small area under cultivation is area under wine, respectively, 12.5 percent of the total area of communities with a medium area under cultivation, and 31.4 percent of the total area of communities with a large area under cultivation. Table 1 gives some characteristics of the Rhineland-Palatinate study region.

Rhineland-Palatinate is the federal state with the most extensive winegrowing in Germany: About 3 percent of the Rhineland-Palatinate area is under wine cultivation. Therefore, a potential pesticide exposure of the residential population might be assumed. Actual deposit measurements in one Rhineland-Palatinate wine district (Moselle region) point to an ongoing insecticide (parathione) and herbicide (atrazine, simazine) exposure of the residential population [20]. Repeatedly, a suspected increase in cancer incidence has been a subject of concern in the mentioned region. The aim of the present ecological study is therefore to investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities compared to the cancer risk among residents of communities with a small area under wine cultivation.

Materials and methods Study population and study area Each Rhineland-Palatinate winegrowing community (n = 503, out of 2,305 communities in Rhineland-Palatinate)

Cancer registry data This study is based on cancer cases registered in the Rhineland-Palatinate cancer registry which covers a population of approximately 4,000,000 persons. We included all malignant tumours plus benign brain and CNS tumours and brain and CNS tumours of uncertain behaviour. Furthermore, we included malignant bladder tumours plus carcinoma in situ and tumours of uncertain behaviour of the bladder. Since January 2000 all Rhineland-Palatinate physicians and dentists are legally obliged to report incident cancer cases to the cancer registry. Therefore, all above mentioned cancers diagnosed between 2000 and 2003 and reported until mid-2005 were included. The following items are registered: diagnosis (ICD-10); topography and morphology (ICD-O-2); staging (TNM); incidence date; most valid basis of diagnosis; occasion of first detection; initial treatment; last occupation and longest held occupation; and date and cause of death (where appropriate). Population figures and data on area under wine cultivation were obtained from the statistical office of Rhineland-Palatinate. Statistical methods Completeness of the Rhineland-Palatinate cancer registry varies with time, region, physician's specialization and type of cancer. This had to be considered in our analysis. Completeness is estimated by the ratio of reported cases to estimated cases for Rhineland-Palatinate calculated from a national pooling of cancer registry data [21,22]. In communities with a small area under wine cultivation, the completeness (excluding non-melanotic skin cancer) is

Table 1: Characteristics of the Rhineland-Palatinate vineyard area

Rhineland-Palatinate* Total Communities Total area (ha) Area under wine (ha) % area under wine Inhabitants (per ha) Inhabitants per community (median, min-max)

2,305 1,984,688 69,043 3.5% 4,000,567 (2.02) 566 (6–184,752)

Area under wine (% of community area) > 0%, ≤ 5% >5%, ≤ 20% >20% 162 222,736 2,996 1.3% 564,210 (2.53) 1,188 (72–99,750)

171 200,709 25,101 12.5% 526,486 (2.62) 1,193 (95–80,535)

170 129,444 40,683 31.4% 301,193 (2.33) 984 (84–40,110)

* All data pertain to Dec 31st, 1996 (Statistisches Landesamt Rheinland-Pfalz 2006)




Table 2: Cancer risks (incidence rate ratios RR) in men with residence in communities with a large or medium area under wine cultivation vs. men in communities with low area under wine cultivation

Reference* (1,665,594 PY†) ICD-10 code Head & neck (C00–C14) Base of tongue (C01) Other and unspecified parts of tongue (C02) Floor of mouth (C04) Palate (C05) Other and unspecified parts of mouth (C06) Parotid gland (C07) Tonsil (C09) Oropharynx (C10) Piriform sinus (C12) Hypopharynx (C13) Oesophagus (C15) Stomach (C16) Small intestine (C17) Colon, sigmoid & rectum (C18–C21) Colon (C18) Rectosigmoid junction (C19) Rectum (C20) Anus and anal canal (C21) Liver and intrahepatic bile ducts (C22) Gallbladder & biliary tract (C23–C24) Gallbladder (C23) Other and unspecified parts of biliary tract (C24) Pancreas (C25) Nasal cavity and middle ear (C30–C31) Larynx (C32) Trachea, bronus and lung (C33–C34) Bronchus and lung (C34) Bone and articular cartilage (C40–C41) Skin, malignant melanoma (C43) Skin, other malignant neoplasms (C44) Mesothelioma (C45) Other connective and soft tissue (C49) Breast (C50) Penis (C60) Prostate (C61) Testis (C62) Urinary tract (C64-C66+C68) Kidney, except renal pelvis (C64) Ureter (C66) Bladder (C67, D09.0, D41.4) Eye and adnexa (C69) Meninges (C70) Brain, CNS, meninges (C70–C72, D32–33, D42– 43) Brain (C71, D33, D43) Thyroid gland (C73) Hodgkin's disease (C81) Follicular NHL (C82) NHL (C82–C85) Diffuse NHL (C83) Peripheral and cutaneous T-cell lymphomas (C84) Other and unspecified types of NHL (C85) Multiple myeloma (C90) Leukaemia (C91–C95) Lymphoid leukaemia (C91)

Cases

Area under wine cultivation > 5, ≤ 20% of community area (1,039,435 PY†) 95% CI Cases RR‡§

Area under wine cultivation > 20% of community area (612,714 PY†) Cases

RR‡§

95% CI

369 35 35 42 22 18 14 47 35 20 56 156 241 24 1188 723 51 397 17 141 76 17 59 162 18 135 1039 1036 11 230 1990 19 32 14 20 1857 154 330 269 30 699 15 22 133

188 11 26 25 15 8 8 22 15 10 27 94 166 14 806 473 42 284 7 73 33 7 26 99 9 78 530 530 7 188 1748 12 35 9 15 1359 107 206 171 7 470 8 20 90

0.91 0.53 1.22 0.98 1.24 0.71 0.92 0.78 0.78 0.90 0.76 0.96 1.06 0.92 1.07 1.04 1.33 1.13 0.66 0.94 0.67 0.58 0.70 1.03 0.73 0.94 0.98 0.98 0.88 1.32 1.32 1.09 1.65 1.02 1.17 1.26 1.18 1.03 1.06 0.35 1.16 1.02 1.45 1.08

0.72–1.15 0.26–1.08 0.72–2.07 0.57–1.70 0.62–2.49 0.29–1.73 0.36–2.30 0.45–1.34 0.39–1.57 0.41–2.02 0.46–1.26 0.73–1.27 0.86–1.31 0.45–1.86 0.95–1.21 0.91–1.20 0.89–2.00 0.94–1.35 0.26–1.64 0.68–1.30 0.44–1.02 0.23–1.46 0.43–1.13 0.78–1.36 0.32–1.67 0.68–1.29 0.84–1.14 0.84–1.15 0.32–2.42 1.08–1.60 1.20–1.45 0.52–2.28 1.00–2.70 0.43–2.39 0.56–2.44 1.12–1.41 0.88–1.60 0.85–1.26 0.86–1.32 0.15–0.80 1.01–1.34 0.43–2.43 0.78–2.69 0.81–1.44

94 10 13 11 5 3 4 13 5 8 17 42 92 2 460 268 30 157 5 37 27 7 20 51 4 39 232 232 3 119 959 5 9 3 6 787 77 107 89 7 266 3 7 53

0.86 0.87 1.12 0.70 0.88 0.45 0.80 0.79 0.48 1.67 0.88 0.82 1.03 0.21 1.10 1.06 1.68 1.10 0.85 0.88 0.95 0.96 0.95 0.96 0.51 0.88 0.77 0.77 0.49 1.50 1.39 0.92 0.68 0.60 0.71 1.26 1.31 0.96 1.00 0.58 1.31 0.88 0.88 1.04

0.65–1.14 0.40–1.91 0.56–2.25 0.34–1.47 0.31–2.54 0.12–1.71 0.24–2.67 0.40–1.56 0.17–1.34 0.66–4.25 0.48–1.62 0.57–1.20 0.79–1.34 0.05–0.95 0.96–1.26 0.90–1.25 1.04–2.71 0.89–1.37 0.29–2.50 0.58–1.32 0.59–1.54 0.36–2.53 0.55–1.65 0.68–1.37 0.16–1.62 0.59–1.31 0.64–0.92 0.64–0.92 0.13–1.89 1.18–1.91 1.25–1.54 0.32–2.68 0.31–1.48 0.16–2.25 0.26–1.93 1.11–1.43 0.94–1.83 0.75–1.23 0.76–1.31 0.24–1.39 1.10–1.55 0.23–3.37 0.35–2.18 0.73–1.49

109 33 40 29 197 122 10 36 63 204 116

70 23 24 21 130 66 6 37 36 113 56

1.02 1.11 0.86 1.23 1.12 0.91 0.94 1.64 0.93 0.89 0.74

0.74–1.41 0.64–1.92 0.51–1.46 0.67–2.25 0.88–1.42 0.66–1.24 0.33–2.68 1.03–2.59 0.60–1.44 0.69–1.15 0.53–1.05

45 16 12 19 81 31 8 23 21 61 28

1.06 1.31 0.64 1.98 1.29 0.80 2.19 1.84 0.92 0.84 0.65

0.72–1.57 0.68–2.53 0.32–1.27 1.01–3.85 0.96–1.73 0.52–1.23 0.75–6.37 1.05–3.23 0.53–1.59 0.61–1.16 0.41–1.02




Table 2: Cancer risks (incidence rate ratios RR) in men with residence in communities with a large or medium area under wine cultivation vs. men in communities with low area under wine cultivation (Continued)

Myeloid leukaemia (C92) Primary site unspecified All malignancies (excluding C44) All malignancies (including C44)

77 128 7761 9751

52 83 5024 6772

1.09 0.99 1.12 1.15

0.75–1.59 0.75–1.30 1.05–1.19 1.09–1.22

27 43 2765 3724

0.99 0.88 1.10 1.16

0.61–1.60 0.61–1.28 1.03–1.18 1.09–1.23

* Winegrowing communities with >0,