The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort
There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very...
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| Veröffentlicht in: | Environmental research 2024-01, Vol.241, p.117562-117562, Article 117562 |
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| creator | Felici, Alessio Peduzzi, Giulia Giorgolo, Francesca Spinelli, Andrea Calderisi, Marco Monreale, Anna Farinella, Riccardo Pellungrini, Roberto Canzian, Federico Campa, Daniele |
| description | There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited.
The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development.
Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out.
Thirty-six statistically significant associations considering multiple testing (p |
| doi_str_mv | 10.1016/j.envres.2023.117562 |
| format | Article |
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The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development.
Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out.
Thirty-six statistically significant associations considering multiple testing (p < 2.19 × 10−4) were observed. Among the novel associations we observed that individuals living farther from the coast had a higher risk of developing prostate cancer (OR = 1.13, CI95% = 1.06–1.20, P = 1.98 × 10−4). This association was partially mediated by physical activity (indirect effect (IE) = -8.48 × 10−7) and the time spent outdoor (IE = 9.07 × 10−6). All PGSs showed statistically significant associations. Finally, genome-environment interaction analysis showed that local environment and genetic variability affect cancer risk independently.
Living close to the coast and air pollution were associated with a decreased risk of prostate cancer and skin melanoma, respectively. These findings from the UKBB support the role of the local environment on cancer development, which is independent from genetics and may be mediated by several lifestyle factors.
•The local environment plays a role in cancer development.•Living far from the coast is associated with an increased risk of prostate cancer.•Many exposures mediate the effect of living far from the coast on prostate cancer.•Local environment exposures and genetics are independent from each other.•Local environment and genetics should be accounted when stratifying for cancer risk.</description><identifier>ISSN: 0013-9351</identifier><identifier>EISSN: 1096-0953</identifier><identifier>DOI: 10.1016/j.envres.2023.117562</identifier><identifier>PMID: 37944693</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Cancer ; Distance to coast ; Gene-environment interactions ; Local environment ; Mediation ; UK Biobank</subject><ispartof>Environmental research, 2024-01, Vol.241, p.117562-117562, Article 117562</ispartof><rights>2023 The Authors</rights><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c408t-7accc299a04d0a28a17b7b1340461d5c856b18741bc0540cdd28e56cd89121703</citedby><cites>FETCH-LOGICAL-c408t-7accc299a04d0a28a17b7b1340461d5c856b18741bc0540cdd28e56cd89121703</cites><orcidid>0000-0002-4261-4583 ; 0009-0003-4116-0203 ; 0009-0009-4313-474X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.envres.2023.117562$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37944693$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Felici, Alessio</creatorcontrib><creatorcontrib>Peduzzi, Giulia</creatorcontrib><creatorcontrib>Giorgolo, Francesca</creatorcontrib><creatorcontrib>Spinelli, Andrea</creatorcontrib><creatorcontrib>Calderisi, Marco</creatorcontrib><creatorcontrib>Monreale, Anna</creatorcontrib><creatorcontrib>Farinella, Riccardo</creatorcontrib><creatorcontrib>Pellungrini, Roberto</creatorcontrib><creatorcontrib>Canzian, Federico</creatorcontrib><creatorcontrib>Campa, Daniele</creatorcontrib><title>The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort</title><title>Environmental research</title><addtitle>Environ Res</addtitle><description>There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited.
The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development.
Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out.
Thirty-six statistically significant associations considering multiple testing (p < 2.19 × 10−4) were observed. Among the novel associations we observed that individuals living farther from the coast had a higher risk of developing prostate cancer (OR = 1.13, CI95% = 1.06–1.20, P = 1.98 × 10−4). This association was partially mediated by physical activity (indirect effect (IE) = -8.48 × 10−7) and the time spent outdoor (IE = 9.07 × 10−6). All PGSs showed statistically significant associations. Finally, genome-environment interaction analysis showed that local environment and genetic variability affect cancer risk independently.
Living close to the coast and air pollution were associated with a decreased risk of prostate cancer and skin melanoma, respectively. These findings from the UKBB support the role of the local environment on cancer development, which is independent from genetics and may be mediated by several lifestyle factors.
•The local environment plays a role in cancer development.•Living far from the coast is associated with an increased risk of prostate cancer.•Many exposures mediate the effect of living far from the coast on prostate cancer.•Local environment exposures and genetics are independent from each other.•Local environment and genetics should be accounted when stratifying for cancer risk.</description><subject>Cancer</subject><subject>Distance to coast</subject><subject>Gene-environment interactions</subject><subject>Local environment</subject><subject>Mediation</subject><subject>UK Biobank</subject><issn>0013-9351</issn><issn>1096-0953</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1v1DAQhi1ERbcf_wAhH7lk8WcSX5CgAopaiUt7tpzxlHqb2IvtXYl_j6sUjpzGIz3zzvgh5C1nW854_2G3xXjMWLaCCbnlfNC9eEU2nJm-Y0bL12TDGJedkZqfkrNSdq3lWrI35FQORqneyA1Z7h6RzgncTFtcyCkuGCt10dOfmJc5RGyPiDUAPbocXA0p0n1GH6BScBEw0xzKEw2R1pZ1f0M_hzS5-NSoVPYINRyRQnpMuV6Qkwc3F7x8qefk_uuXu6vr7vbHt-9Xn247UGys3eAAQBjjmPLMidHxYRomLhVTPfcaRt1PfBwUn4BpxcB7MaLuwY-GCz4weU7er7nthF8HLNUuoQDOs4uYDsWKcTRC6YHLhqoVhXZtyfhg9zksLv-2nNln0XZnV9H2WbRdRbexdy8bDtOC_t_QX7MN-LgC2P55DJhtgYBNlw-5ObE-hf9v-ANlCZFp</recordid><startdate>20240115</startdate><enddate>20240115</enddate><creator>Felici, Alessio</creator><creator>Peduzzi, Giulia</creator><creator>Giorgolo, Francesca</creator><creator>Spinelli, Andrea</creator><creator>Calderisi, Marco</creator><creator>Monreale, Anna</creator><creator>Farinella, Riccardo</creator><creator>Pellungrini, Roberto</creator><creator>Canzian, Federico</creator><creator>Campa, Daniele</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-4261-4583</orcidid><orcidid>https://orcid.org/0009-0003-4116-0203</orcidid><orcidid>https://orcid.org/0009-0009-4313-474X</orcidid></search><sort><creationdate>20240115</creationdate><title>The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort</title><author>Felici, Alessio ; Peduzzi, Giulia ; Giorgolo, Francesca ; Spinelli, Andrea ; Calderisi, Marco ; Monreale, Anna ; Farinella, Riccardo ; Pellungrini, Roberto ; Canzian, Federico ; Campa, Daniele</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c408t-7accc299a04d0a28a17b7b1340461d5c856b18741bc0540cdd28e56cd89121703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cancer</topic><topic>Distance to coast</topic><topic>Gene-environment interactions</topic><topic>Local environment</topic><topic>Mediation</topic><topic>UK Biobank</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Felici, Alessio</creatorcontrib><creatorcontrib>Peduzzi, Giulia</creatorcontrib><creatorcontrib>Giorgolo, Francesca</creatorcontrib><creatorcontrib>Spinelli, Andrea</creatorcontrib><creatorcontrib>Calderisi, Marco</creatorcontrib><creatorcontrib>Monreale, Anna</creatorcontrib><creatorcontrib>Farinella, Riccardo</creatorcontrib><creatorcontrib>Pellungrini, Roberto</creatorcontrib><creatorcontrib>Canzian, Federico</creatorcontrib><creatorcontrib>Campa, Daniele</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Felici, Alessio</au><au>Peduzzi, Giulia</au><au>Giorgolo, Francesca</au><au>Spinelli, Andrea</au><au>Calderisi, Marco</au><au>Monreale, Anna</au><au>Farinella, Riccardo</au><au>Pellungrini, Roberto</au><au>Canzian, Federico</au><au>Campa, Daniele</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort</atitle><jtitle>Environmental research</jtitle><addtitle>Environ Res</addtitle><date>2024-01-15</date><risdate>2024</risdate><volume>241</volume><spage>117562</spage><epage>117562</epage><pages>117562-117562</pages><artnum>117562</artnum><issn>0013-9351</issn><eissn>1096-0953</eissn><abstract>There is a growing body of evidence on the effect of the local environment exposure on cancer susceptibility. Nonetheless, several of the associations remain controversial. Moreover, our understanding of the possible interaction between the local environment and the genetic variability is still very limited.
The aim of this study was to clarify the role of the local environment and its possible interplay with genetics on common cancers development.
Using the UK Biobank (UKBB) prospective cohort, we selected 12 local environment exposures: nitrogen oxides, nitrogen dioxides, particulate matter (10 and 2.5 μm), noise pollution, urban traffic, living distance from the coast, percentage of greenspace, natural environment, water, and domestic garden within 1000 m from the residential coordinates of each participant. All these exposures were tested for association with 17 different types of cancer for a total of 53,270 cases and 302,645 controls. Additionally, a polygenic score (PGS) was computed for each cancer, to test possible gene-environment interactions. Finally, mediation analyses were carried out.
Thirty-six statistically significant associations considering multiple testing (p < 2.19 × 10−4) were observed. Among the novel associations we observed that individuals living farther from the coast had a higher risk of developing prostate cancer (OR = 1.13, CI95% = 1.06–1.20, P = 1.98 × 10−4). This association was partially mediated by physical activity (indirect effect (IE) = -8.48 × 10−7) and the time spent outdoor (IE = 9.07 × 10−6). All PGSs showed statistically significant associations. Finally, genome-environment interaction analysis showed that local environment and genetic variability affect cancer risk independently.
Living close to the coast and air pollution were associated with a decreased risk of prostate cancer and skin melanoma, respectively. These findings from the UKBB support the role of the local environment on cancer development, which is independent from genetics and may be mediated by several lifestyle factors.
•The local environment plays a role in cancer development.•Living far from the coast is associated with an increased risk of prostate cancer.•Many exposures mediate the effect of living far from the coast on prostate cancer.•Local environment exposures and genetics are independent from each other.•Local environment and genetics should be accounted when stratifying for cancer risk.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>37944693</pmid><doi>10.1016/j.envres.2023.117562</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-4261-4583</orcidid><orcidid>https://orcid.org/0009-0003-4116-0203</orcidid><orcidid>https://orcid.org/0009-0009-4313-474X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer Distance to coast Gene-environment interactions Local environment Mediation UK Biobank |
| title | The local environment and germline genetic variation predict cancer risk in the UK Biobank prospective cohort |
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