Effect of pesticide exposure on HER-2/neu overexpression seen in patients with extensive stage small cell lung carcinoma.
OBJECTIVE
The aim of this study was to evaluate the relationship, if any, between pesticide exposure and overexpression of the HER-2/neu oncoprotein in extensive stage small cell lung cancer (ESSCLC).


METHODS
The records of all patients with a diagnosis of ESSCLC from January 1991 through April 2001 were reviewed in our retrospective study. Pesticide risk (herbicide and insecticide) was assessed by telephone interviews using a predetermined questionnaire with emphasis on type of exposure, use of protective measures, and duration of exposure. An exposure index was calculated (h/day x days/year x years), and patients with an index > 2400 h were considered as exposed. HER-2/neu overexpression was assessed by immunohistochemistry using the Hercep test developed by Dako. Statistical analysis was performed using SPSS-10.


RESULTS
A total of 193 patients (84 females and 109 males), with a mean age of 68.5 years (range, 42-90 years) were included in the study. Of these, 57 (29.5%) revealed HER-2/neu overexpression by immunohistochemistry. After adjusting for age, smoking, Eastern Cooperative Oncology Group score, and treatment, HER-2/neu overexpression was associated with a statistically significant diminished survival (P < 0.001; Mann-Whitney U test). We contacted 53 of 57 patients with overexpression and 121 of 136 patients without HER-2/neu overexpression to ascertain a history of pesticide exposure. Forty-one of 53 (77.4%) patients with HER-2/neu overexpression and 47 of the 121 patients without overexpression (38.8%) were exposed to pesticides. We found that patients with history of pesticide exposure had a higher risk of having HER-2/neu overexpression (odds ratio, 5.38; P < 0.01, 95% confidence interval, 2.5-11.2)


CONCLUSIONS
HER-2/neu is overexpressed in approximately 30% patients with ESSCLC and is associated with decreased survival. Also, pesticide exposure seems to be related to HER-2/neu overexpression seen in our patient population. Future studies are needed to validate our findings and also to determine which pesticide(s)/pesticide components are actually responsible for HER-2/neu overexpression seen in ESSCLC.
Department of Medicine, University of North Dakota School of Medicine, Fargo, North Dakota 58102, USA. apotti@medicine.nodak.edu
Anil
A
Potti
Apar Kishor
AK
Ganti
Kaley
K
Sholes
Eric
E
Langness
Vijay
V
Koka
Linda
L
Horvarth
Michael
M
Koch
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000139:chemically induced / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010575:Pesticides / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D011795:Surveys and Questionnaires; D013997:Time Factors
D010575:Pesticides; D018719:Erb-b2 Receptor Tyrosine Kinases