Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1

Anna Maria Rossi; Inger-Lise Hansteen; Camilla Furu Skjelbred; Michela Ballardin; Valentina Maggini; Elena Murgia; Antonio Tomei; Paolo Viarengo; Lisbeth E Knudsen; Roberto Barale; Hannu Norppa; Stefano Bonassi

doi:10.1289/ehp.11769

Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1

Anna Maria Rossi, Inger-Lise Hansteen, Camilla Furu Skjelbred, Michela Ballardin, Valentina Maggini, Elena Murgia, Antonio Tomei, Paolo Viarengo, Lisbeth E Knudsen, Roberto Barale, Hannu Norppa, Stefano Bonassi

26 Citations (Scopus)

Abstract

BACKGROUND: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. OBJECTIVES: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. METHODS: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. RESULTS: The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8). CONCLUSIONS: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.

Original language	English
Journal	Environmental Health Perspectives
Volume	117
Issue number	2
Pages (from-to)	203-8
Number of pages	5
ISSN	0091-6765
DOIs	https://doi.org/10.1289/ehp.11769
Publication status	Published - 2009

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10.1289/ehp.11769

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Rossi, A. M., Hansteen, I-L., Skjelbred, C. F., Ballardin, M., Maggini, V., Murgia, E., Tomei, A., Viarengo, P., Knudsen, L. E., Barale, R., Norppa, H., & Bonassi, S. (2009). Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1. Environmental Health Perspectives, 117(2), 203-8. https://doi.org/10.1289/ehp.11769

Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1. / Rossi, Anna Maria; Hansteen, Inger-Lise; Skjelbred, Camilla Furu et al.

In: Environmental Health Perspectives, Vol. 117, No. 2, 2009, p. 203-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Rossi, AM, Hansteen, I-L, Skjelbred, CF, Ballardin, M, Maggini, V, Murgia, E, Tomei, A, Viarengo, P, Knudsen, LE, Barale, R, Norppa, H & Bonassi, S 2009, 'Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1', Environmental Health Perspectives, vol. 117, no. 2, pp. 203-8. https://doi.org/10.1289/ehp.11769

@article{996bb350002011df825d000ea68e967b,

title = "Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1",

abstract = "BACKGROUND: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. OBJECTIVES: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. METHODS: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. RESULTS: The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8). CONCLUSIONS: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.",

author = "Rossi, {Anna Maria} and Inger-Lise Hansteen and Skjelbred, {Camilla Furu} and Michela Ballardin and Valentina Maggini and Elena Murgia and Antonio Tomei and Paolo Viarengo and Knudsen, {Lisbeth E} and Roberto Barale and Hannu Norppa and Stefano Bonassi",

note = "Keywords: Adult; Chromosome Aberrations; Female; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Male; Middle Aged; Neoplasms; Polymorphism, Genetic; Risk",

year = "2009",

doi = "10.1289/ehp.11769",

language = "English",

volume = "117",

pages = "203--8",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "National Institute of Environmental Health Sciences",

number = "2",

}

TY - JOUR

T1 - Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1

AU - Rossi, Anna Maria

AU - Hansteen, Inger-Lise

AU - Skjelbred, Camilla Furu

AU - Ballardin, Michela

AU - Maggini, Valentina

AU - Murgia, Elena

AU - Tomei, Antonio

AU - Viarengo, Paolo

AU - Knudsen, Lisbeth E

AU - Barale, Roberto

AU - Norppa, Hannu

AU - Bonassi, Stefano

N1 - Keywords: Adult; Chromosome Aberrations; Female; Genetic Predisposition to Disease; Genotype; Glutathione Transferase; Humans; Male; Middle Aged; Neoplasms; Polymorphism, Genetic; Risk

PY - 2009

Y1 - 2009

N2 - BACKGROUND: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. OBJECTIVES: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. METHODS: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. RESULTS: The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8). CONCLUSIONS: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.

AB - BACKGROUND: The frequency of chromosomal aberrations (CA) in peripheral blood lymphocytes of healthy individuals has been associated with cancer risk. It is presently unclear whether this association is influenced by individual susceptibility factors such as genetic polymorphisms of xenobiotic-metabolizing enzymes. OBJECTIVES: To evaluate the role of polymorphisms in glutathione S-transferase (GST) M1 (GSTM1) and theta 1 (GSTT1) as effect modifiers of the association between CA and cancer risk. METHODS: A case-control study was performed pooling data from cytogenetic studies carried out in 1974-1995 in three laboratories in Italy, Norway, and Denmark. A total of 107 cancer cases were retrieved from national registries and matched to 291 controls. The subjects were classified as low, medium, and high by tertile of CA frequency. The data were analyzed by setting up a Bayesian model that included prior information about cancer risk by CA frequency. RESULTS: The association between CA frequency and cancer risk was confirmed [OR(medium) (odds ratio)(medium) = 1.5, 95% credibility interval (CrI), 0.9-2.5; OR(high) = 2.8, 95% CrI, 1.6-4.6], whereas no effect of the genetic polymorphism was observed. A much stronger association was seen in the Italian subset (OR(high)= 9.4, 95% CrI, 2.6-28.0), which was characterized by a lower technical variability of the cytogenetic analysis. CA level was particularly associated with cancer of the respiratory tract (OR(high)= 6.2, 95% CrI, 1.5-20.0), the genitourinary tract (OR(high) = 4.0, 95% CrI, 1.4-10.0), and the digestive tract (OR(high) = 2.8, 95% CrI, 1.2-5.8). CONCLUSIONS: Despite the small size of the study groups, our results substantiate the cancer risk predictivity of CA frequency, ruling against a strong modifying effect of GSTM1 and GSTT1 polymorphisms.

U2 - 10.1289/ehp.11769

DO - 10.1289/ehp.11769

M3 - Journal article

C2 - 19270789

SN - 0091-6765

VL - 117

SP - 203

EP - 208

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

IS - 2

ER -

Association between frequency of chromosomal aberrations and cancer risk is not influenced by genetic polymorphisms in GSTM1 and GSTT1

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