Europ. J. CancerVol. 13, pp. 1405-1409. Pergamon Press 1977. Printed in Great Britain
Possible Relationship of Plasma IgA, IgG and IgM to Breast Cancer in British and Japanese Women D. Y. WANG,* P. R. GOODWIN,* R. D. BULBROOK,* J. L. HAYWARD,~ O. ABE, + J. UTSUNOMIYA§ and S. KUMAOKAI[ *Department of Clinical Endocrinology, Imperial Cancer Resear¢h Fund Laboratories, Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom t lCRF Breast Cancer Unit, Guy's Hospital, London, SE1 9R T, United Kingdom +Keio University, Tokyo, Japan § Tokyo Medical and Dental Hospital, Tokyo, Japan and [[National Cancer Centre, Tokyo, Japan Abstract--Plasma levels of IgA, IgG and IgM have been measured in 35 British and 37 Japanese normal adult women, in 22 British and 22 Japanese adolescent girls and in 30 Japanese women with breast cancer. Japanese women had significantly higher blood concentrations of IgG and IgM than British women. The amounts of plasma immunoglobulins in adolescentBritish and Japanese girls were similar to those in adults of the same race, except for IgG, where Japanese adolescent girls had significantly lower levels than in adult Japanese women. In contrast to previous results showing no difference between the IgA, IgG and IgM levels of normal British women and patients with breast cancer, the IgM concentration was significantly lower in the Japanese patients comparedwith that in Japanese controls.
INTRODUCTION
MATERIAL AND M E T H O D S
WE HAVEbeen investigating various factors that might be related to geographical variation in the incidence of breast cancer. So far we have been unable to find any convincing difference in the endocrine function of normal British and Japanese women that could account for the marked difference in incidence [1-3], but 57% of Japanese patients with breast cancer have been shown to have a moderate or marked degree of sinus histiocytosi,; in their lymph nodes compared to only 4% in British patients [4]. Also the degree of lymphocyte infiltration is greater in tumours from Japanese patients than in those from Caucasian women [5]. These findings indicate a racial difference in cell-mediated re,;ponse to breast cancer and prompted the investigation of humoral immune status by determining the concentration of plasma IgA, IgG and IgM in normal British and Japanese women and in Japanese patients with breast cancer.
Accepted26 May 1977. 1405
Subjects
The general organization of the study and details of height, weight and menstrual history of the normal women have been reported [1]. The number, mean age and age range of the various groups studied are given in Table 1. The 30 Japanese and 22 British women with breast cancer hadeither Stage 1 or 2 disease. Blood was taken from these women 3-6 months after mastectomy. Methods
The immunoglobulins IgA, IgG and IgM were measured by rocket immunoelectrophoresis [6]. Standards for igA, IgG and IgM were commercially obtained from Millipore (UK) Ltd. In a previous publication [7] it has been demonstrated that the strength of these standards using W H O figures (1 i.u. is equivalent to 14.2 #g IgA, 80.4 #g IgG and 8.47 #g I g M ) w a s remarkably similar to the potency obtained when they were compared to the M R C reference
D. Y. Wang et al.
1406
Table 1. Number and age oJ women studied Category
No.
Mean age
Age range
British adolescents Japanese adolescents British adults Japanese adults British patients with breast cancer Japanese patients with breast cancer
22 22 35 37
17.3 18.7 52.7 49.6
16w 16 19 35-68 35-66
"
22
56.6
44-68
30
50.9
37-64
preparation (67/99) of IgA, IgG and IgM [7]. Thus all results have been expressed as i.u./ml as advocated by WHO. Included in each batch of 8 samples analysed was a quality control plasma. If the results for the quality control were greater than 15% from the mean value of IgA, IgG or IgM, the batch of samples was assayed again. Precision of the assay as calculated by comparing duplicate estimations showed that the coefficient of variations, in the range studied, was 12.6, 6.4 and 5.3°;o for IgA, IgG and IgM respectively [7]. RESULTS
2. Patients with breast cancer
1. Normal British and Japanese women IgA. There was no statistical difference between the geometric mean level of plasma IgA in normal British and Japanese women nor did the level found l n t h e adoleScent girls differ from those found in the adults (see Table 2; Fig. 1 ). IgG. The geometric mean plasma level of IgG was significantly higher in Japanese women than in British women (t=3.4; P
Possible Relationship of Plasma IgA, IgG and IgM to Breast Cancer in British and Japanese Women D. Y. WANG,* P. R. GOODWIN,* R. D. BULBROOK,* J. L. HAYWARD,~ O. ABE, + J. UTSUNOMIYA§ and S. KUMAOKAI[ *Department of Clinical Endocrinology, Imperial Cancer Resear¢h Fund Laboratories, Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom t lCRF Breast Cancer Unit, Guy's Hospital, London, SE1 9R T, United Kingdom +Keio University, Tokyo, Japan § Tokyo Medical and Dental Hospital, Tokyo, Japan and [[National Cancer Centre, Tokyo, Japan Abstract--Plasma levels of IgA, IgG and IgM have been measured in 35 British and 37 Japanese normal adult women, in 22 British and 22 Japanese adolescent girls and in 30 Japanese women with breast cancer. Japanese women had significantly higher blood concentrations of IgG and IgM than British women. The amounts of plasma immunoglobulins in adolescentBritish and Japanese girls were similar to those in adults of the same race, except for IgG, where Japanese adolescent girls had significantly lower levels than in adult Japanese women. In contrast to previous results showing no difference between the IgA, IgG and IgM levels of normal British women and patients with breast cancer, the IgM concentration was significantly lower in the Japanese patients comparedwith that in Japanese controls.
INTRODUCTION
MATERIAL AND M E T H O D S
WE HAVEbeen investigating various factors that might be related to geographical variation in the incidence of breast cancer. So far we have been unable to find any convincing difference in the endocrine function of normal British and Japanese women that could account for the marked difference in incidence [1-3], but 57% of Japanese patients with breast cancer have been shown to have a moderate or marked degree of sinus histiocytosi,; in their lymph nodes compared to only 4% in British patients [4]. Also the degree of lymphocyte infiltration is greater in tumours from Japanese patients than in those from Caucasian women [5]. These findings indicate a racial difference in cell-mediated re,;ponse to breast cancer and prompted the investigation of humoral immune status by determining the concentration of plasma IgA, IgG and IgM in normal British and Japanese women and in Japanese patients with breast cancer.
Accepted26 May 1977. 1405
Subjects
The general organization of the study and details of height, weight and menstrual history of the normal women have been reported [1]. The number, mean age and age range of the various groups studied are given in Table 1. The 30 Japanese and 22 British women with breast cancer hadeither Stage 1 or 2 disease. Blood was taken from these women 3-6 months after mastectomy. Methods
The immunoglobulins IgA, IgG and IgM were measured by rocket immunoelectrophoresis [6]. Standards for igA, IgG and IgM were commercially obtained from Millipore (UK) Ltd. In a previous publication [7] it has been demonstrated that the strength of these standards using W H O figures (1 i.u. is equivalent to 14.2 #g IgA, 80.4 #g IgG and 8.47 #g I g M ) w a s remarkably similar to the potency obtained when they were compared to the M R C reference
D. Y. Wang et al.
1406
Table 1. Number and age oJ women studied Category
No.
Mean age
Age range
British adolescents Japanese adolescents British adults Japanese adults British patients with breast cancer Japanese patients with breast cancer
22 22 35 37
17.3 18.7 52.7 49.6
16w 16 19 35-68 35-66
"
22
56.6
44-68
30
50.9
37-64
preparation (67/99) of IgA, IgG and IgM [7]. Thus all results have been expressed as i.u./ml as advocated by WHO. Included in each batch of 8 samples analysed was a quality control plasma. If the results for the quality control were greater than 15% from the mean value of IgA, IgG or IgM, the batch of samples was assayed again. Precision of the assay as calculated by comparing duplicate estimations showed that the coefficient of variations, in the range studied, was 12.6, 6.4 and 5.3°;o for IgA, IgG and IgM respectively [7]. RESULTS
2. Patients with breast cancer
1. Normal British and Japanese women IgA. There was no statistical difference between the geometric mean level of plasma IgA in normal British and Japanese women nor did the level found l n t h e adoleScent girls differ from those found in the adults (see Table 2; Fig. 1 ). IgG. The geometric mean plasma level of IgG was significantly higher in Japanese women than in British women (t=3.4; P
