Somatic Loss of the Y Chromosome is Associated with Arsenic Exposure Among Bangladeshi Men

Overview

Journal Int J Epidemiol

Specialty Public Health

Date 2022 Sep 21

PMID 36130227

Authors

Kathryn Demanelis

Dayana A Delgado

Lin Tong

Farzana Jasmine

Alauddin Ahmed

Tariqul Islam

Faruque Parvez

Muhammad G Kibriya

Joseph H Graziano

Habibul Ahsan

Brandon L Pierce

Affiliations

Soon will be listed here.

Abstract

Background: Arsenic exposure increases the risk of several cancers in humans and contributes to genomic instability. Somatic loss of the Y chromosome (LoY) is a potential biomarker of genomic instability and cancer risk. Smoking is associated with LoY, but few other carcinogens have been investigated. We tested the cross-sectional association between arsenic exposure and LoY in leukocytes among genotyped Bangladeshi men (age 20-70 years) from the Health Effects of Arsenic Longitudinal Study.

Methods: We extracted the median of logR-ratios from probes on the Y chromosome (mLRR-chrY) from genotyping arrays (n = 1364) and estimated the percentage of cells with LoY (% LoY) from mLRR-chrY. We evaluated the association between arsenic exposure (measured in drinking water and urine) and LoY using multivariable linear and logistic regression models. The association between LoY and incident arsenic-induced skin lesions was also examined.

Results: Ten percent of genotyped men had LoY in at least 5% of cells and % LoY increased with age. Among men randomly selected for genotyping (n = 778), higher arsenic in drinking water, arsenic consumed and urinary arsenic were associated with increased % LoY (P = 0.006, P = 0.06 and P = 0.13, respectively). LoY was associated with increased risk of incident skin lesions (P = 0.008).

Conclusion: Arsenic exposure was associated with increased LoY, providing additional evidence that arsenic contributes to genomic instability. LoY was associated with developing skin lesions, a risk factor for cancer, suggesting that LoY may be a biomarker of susceptibility in arsenic-exposed populations. The effect of arsenic on somatic events should be further explored in cancer-prone tissue types.

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References

Celik I, Gallicchio L, Boyd K, Lam T, Matanoski G, Tao X . Arsenic in drinking water and lung cancer: a systematic review. Environ Res. 2008; 108(1):48-55. DOI: 10.1016/j.envres.2008.04.001. View

Moon K, Oberoi S, Barchowsky A, Chen Y, Guallar E, Nachman K . A dose-response meta-analysis of chronic arsenic exposure and incident cardiovascular disease. Int J Epidemiol. 2017; 46(6):1924-1939. PMC: 5837344. DOI: 10.1093/ije/dyx202. View

Wojdacz T, Bottai M, Vahter M, Broberg K . Exposure to arsenic and intra-chromosomal instability in blood. Metallomics. 2014; 6(8):1387-9. DOI: 10.1039/c4mt00128a. View

Danielsson M, Halvardson J, Davies H, Moghadam B, Mattisson J, Rychlicka-Buniowska E . Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals. Eur J Hum Genet. 2019; 28(3):349-357. PMC: 7028735. DOI: 10.1038/s41431-019-0533-z. View

Niedzwiecki M, Liu X, Zhu H, Hall M, Slavkovich V, Ilievski V . Serum homocysteine, arsenic methylation, and arsenic-induced skin lesion incidence in Bangladesh: A one-carbon metabolism candidate gene study. Environ Int. 2018; 113:133-142. PMC: 5873983. DOI: 10.1016/j.envint.2018.01.015. View

Chen Y, Wu F, Liu M, Parvez F, Slavkovich V, Eunus M . A prospective study of arsenic exposure, arsenic methylation capacity, and risk of cardiovascular disease in Bangladesh. Environ Health Perspect. 2013; 121(7):832-8. PMC: 3701993. DOI: 10.1289/ehp.1205797. View

Dangleben N, Skibola C, Smith M . Arsenic immunotoxicity: a review. Environ Health. 2013; 12(1):73. PMC: 3848751. DOI: 10.1186/1476-069X-12-73. View

Forsberg L, Halvardson J, Rychlicka-Buniowska E, Danielsson M, Moghadam B, Mattisson J . Mosaic loss of chromosome Y in leukocytes matters. Nat Genet. 2018; 51(1):4-7. DOI: 10.1038/s41588-018-0267-9. View

Sanchez T, Powers M, Perzanowski M, George C, Graziano J, Navas-Acien A . A Meta-analysis of Arsenic Exposure and Lung Function: Is There Evidence of Restrictive or Obstructive Lung Disease?. Curr Environ Health Rep. 2018; 5(2):244-254. PMC: 6149528. DOI: 10.1007/s40572-018-0192-1. View

10.

Gamboa-Loira B, Cebrian M, Franco-Marina F, Lopez-Carrillo L . Arsenic metabolism and cancer risk: A meta-analysis. Environ Res. 2017; 156:551-558. DOI: 10.1016/j.envres.2017.04.016. View

11.

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

12.

Hsu L, Chen G, Lee C, Yang T, Chen Y, Wang Y . Use of arsenic-induced palmoplantar hyperkeratosis and skin cancers to predict risk of subsequent internal malignancy. Am J Epidemiol. 2013; 177(3):202-12. DOI: 10.1093/aje/kws369. View

13.

Nermell B, Lindberg A, Rahman M, Berglund M, Persson L, El Arifeen S . Urinary arsenic concentration adjustment factors and malnutrition. Environ Res. 2007; 106(2):212-8. DOI: 10.1016/j.envres.2007.08.005. View

14.

Dumanski J, Lambert J, Rasi C, Giedraitis V, Davies H, Grenier-Boley B . Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease. Am J Hum Genet. 2016; 98(6):1208-1219. PMC: 4908225. DOI: 10.1016/j.ajhg.2016.05.014. View

15.

Sanchez T, Slavkovich V, LoIacono N, van Geen A, Ellis T, Chillrud S . Urinary metals and metal mixtures in Bangladesh: Exploring environmental sources in the Health Effects of Arsenic Longitudinal Study (HEALS). Environ Int. 2018; 121(Pt 1):852-860. PMC: 6231410. DOI: 10.1016/j.envint.2018.10.031. View

16.

Martinez V, Vucic E, Becker-Santos D, Gil L, Lam W . Arsenic exposure and the induction of human cancers. J Toxicol. 2011; 2011:431287. PMC: 3235889. DOI: 10.1155/2011/431287. View

17.

Cantu E, Moses M, Nemana L, Pierre R . Sex chromosome loss in adults with haematological neoplasms. Br J Haematol. 2014; 169(6):899-901. DOI: 10.1111/bjh.13251. View

18.

Sciandrello G, Barbaro R, Caradonna F, Barbata G . Early induction of genetic instability and apoptosis by arsenic in cultured Chinese hamster cells. Mutagenesis. 2002; 17(2):99-103. DOI: 10.1093/mutage/17.2.99. View

19.

Saint-Jacques N, Parker L, Brown P, Dummer T . Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence. Environ Health. 2014; 13:44. PMC: 4088919. DOI: 10.1186/1476-069X-13-44. View

20.

Forsberg L . Loss of chromosome Y (LOY) in blood cells is associated with increased risk for disease and mortality in aging men. Hum Genet. 2017; 136(5):657-663. PMC: 5418310. DOI: 10.1007/s00439-017-1799-2. View