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ABO blood type is associated with endometrial cancer risk in Chinese women.
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PMID:  22035857     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ABO blood type has been associated with risk of several malignancies. However, results are not consistent. In this population-based case-control study including 1204 incident endometrial cancer cases and 1212 population controls, we examined the association of self-reported serologic blood type with endometrial cancer risk using a logistic regression model. Women with endometrial cancer were more likely to have blood type A. Compared to women with blood type O, the adjusted odds ratios for endometrial cancer were 1.00 [95% confidence interval (CI), 0.79-1.28] for type B, 1.24 (95% CI, 0.90-1.69) for type AB, and 1.50 (95% CI, 1.19-1.90) for type A. A significant dose-response relationship was observed for cancer risk and level of antigen A (P for trend = 0.0003). The positive association of blood type A with cancer risk was observed regardless of menopausal status, body mass index, oral contraceptive use, or family cancer history. Our results suggest that ABO blood type may be involved in the development of endometrial cancer.
Authors:
Wang-Hong Xu; Wei Zheng; Yong-Bing Xiang; Xiao-Ou Shu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Chinese journal of cancer     Volume:  30     ISSN:  1000-467X     ISO Abbreviation:  Chin J Cancer     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-31     Completed Date:  2013-01-31     Revised Date:  2013-12-10    
Medline Journal Info:
Nlm Unique ID:  101498232     Medline TA:  Chin J Cancer     Country:  China    
Other Details:
Languages:  eng     Pagination:  766-71     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ABO Blood-Group System*
Adult
Aged
Body Mass Index
Case-Control Studies
China / epidemiology
Confidence Intervals
Contraceptives, Oral / adverse effects
Endometrial Neoplasms / blood*,  chemically induced,  etiology
Female
Humans
Logistic Models
Middle Aged
Odds Ratio
Risk Factors
Grant Support
ID/Acronym/Agency:
R01 CA092585/CA/NCI NIH HHS; R01CA92585/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/ABO Blood-Group System; 0/Contraceptives, Oral
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Journal Information
Journal ID (nlm-ta): Chin J Cancer
Journal ID (iso-abbrev): Chin J Cancer
Journal ID (publisher-id): CJC
ISSN: 1000-467X
ISSN: 1944-446X
Publisher: Sun Yat-sen University Cancer Center
Article Information
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Chinese Journal of Cancer
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Received Day: 27 Month: 7 Year: 2011
Revision Received Day: 2 Month: 9 Year: 2011
Accepted Day: 7 Month: 9 Year: 2011
Print publication date: Month: 11 Year: 2011
Volume: 30 Issue: 11
First Page: 766 Last Page: 771
PubMed Id: 22035857
ID: 3829717
Publisher Id: cjc-30-11-766
DOI: 10.5732/cjc.011.10305

ABO blood type is associated with endometrial cancer risk in Chinese women
Wang-Hong Xu1
Wei Zheng2
Yong-Bing Xiang3
Xiao-Ou Shu2
1Department of Epidemiology, School of Public Health, Fudan University; Key Laboratory of Public Health Safety, Ministry of Education (Fudan University), Shanghai 200032, P. R. China;
2Vanderbilt Epidemiology Center, Department of Medicine and Vanderbilt-lngram Cancer Center, Nashville, TN 37232-8300, USA;
3Department of Epidemiology, Shanghai Cancer Institute, Shanghai 200032, P. R. China.
Correspondence: Corresponding Author: Wang-Hong Xu, Department of Epidemiology, School of Public Health, Fudan University, 138 Yixueyuan Road, Shanghai 200032, P. R. China. Tel: +86-21-54237679; Fax: +86-21-54237334; Email: wanghong.xu@fudan.edu.cn.

Since Aird et al.[1] first reported an association between blood type A and gastric cancer in 1953, numerous reports have documented a high incidence of cancers of the stomach[2], pancreas[3], gallbladder[4], lung[5], kidney[6], breast[7],[8], ovaries[9], and uterus[10] for blood type A or B, suggesting a role for inherited human blood group antigens in the development of cancer. Recently, Amundadottir et al.[11] conducted a genome-wide association study (PanScan) and identified significant associations of the ABO gene locus with the risk of pancreatic cancer, sparking a new wave of interest in the role of ABO blood types in the development of cancer. More recently, Wolpin et al.[12] observed a significantly elevated risk for incident pancreatic cancer among participants with blood types A or B compared to those with blood type O. This result was subsequently confirmed in 1534 cases and 1583 controls from 12 prospective cohorts in PanScan[13]. The association of ABO blood type with gastric cancer[14], breast cancer[15], and skin cancer[16] has also been investigated in recent years, but the results have been inconsistent. In this study, we evaluated the association of blood types with endometrial cancer risk using data from the Shanghai Endometrial Cancer Study, a large population-based case-control study conducted in urban Shanghai, China[17].


Materials and Methods
Study subjects

Using the population-based Shanghai Cancer Registry, we identified 1 449 eligible endometrial cancer case subjects, ranging in age from 30 to 69, who were diagnosed with the malignancy between 1997 and 2003. Cancer diagnosis was confirmed by review of medical records and available pathologic slides. A total of 1204 case subjects completed in-person interviews and were included in this study.

Control subjects were randomly selected from the general population of Shanghai using the Shanghai Resident Registry, and were matched to cases according to the age distribution of endometrial cancer cases in 1996. Women with a history of cancer or hysterectomy were excluded. Of the 1629 eligible women contacted, 1212 (74.4%) participated in the study. The study protocols were approved by the Institutional Review Boards of all institutes involved in the study, and written informed consent was obtained from all participants prior to participation in the study.

Data collection

Study participants were interviewed in person by trained, retired medical professionals. A structured questionnaire was used to elicit detailed information on Serologic blood types (A, AB, B, O, unknown), demographic factors, menstrual and reproductive history, hormone use, prior disease history, dietary habits, physical activity, tobacco and alcohol use, body weight, and family history of cancer. Anthropometrics (weight, height, and waist and hip circumferences) were also taken during the interview using a standard protocol.

Statistical analyses

Chi-square (χ2) test or t test were used to evaluate case-control differences in demographic and lifestyle characteristics. χ2 test or ANOVA test was used to compare the characteristics among the four blood type groups. The risk of endometrial cancer associated with blood types was estimated by odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression with adjustment for age and potential confounders. All statistical tests were applied using SAS software (version 9.1) and were based on two-tailed probability.


Results

The descriptive characteristics of cases and controls are shown in Table 1. There were no significant case-control differences with regard to age and hormone replacement therapy (all P > 0.05). However, compared with controls, case subjects were more likely to have higher education, history of diabetes mellitus, more cumulative years of menstruation, fewer pregnancies, higher body mass index (BMI), and positive family history of cancer. In addition, case subjects were less likely to exercise, drink alcohol, or use oral contraceptives.

The frequencies of blood types O, B, AB, and A were 36.6%, 25.7%, 12.0%, and 25.7%, respectively, among our control participants. Due to lack of related data from the general population in Shanghai, we compared the frequency distribution of ABO blood types in our control group with that from blood donors in Shanghai[18] and the controls in the Shanghai Breast Cancer Study (SBCS), a large-scale population-based case-control study conducted in Shanghai between 1996 and 1998[19]. The frequency distribution of ABO blood types in our control group was significantly different from that in blood donors (P for χ2 test = 0.002) but did not differ from that in the SBCS control group (P for χ2 test = 0.34) (Table 2).

The characteristics of control participants according to self-reported ABO blood types are presented in Table 3. Women with different ABO blood types were comparable in educational level, postmenopausal status, time of menstruation, number of pregnancies, family history of cancer, history of diabetes, cigarette smoking, alcohol drinking, and BMI. However, a significant difference existed for average age, use of hormone replacement therapy, and use of oral contraceptives.

As shown in Table 4, women with endometrial cancer were more likely than controls to have blood type A. Given that the individuals with blood type O have neither A nor B antigens on the surface of their red cells, the women with the blood type were used as reference in the study. Adjusted OR was 1.50 (95% CI = 1.19–1.90) for blood type A as compared with blood type O. A moderately increased but not statistically significant risk was observed for women with blood type AB compared with women with blood type O (OR = 1.24, 95% CI = 0.90–1.69). These positive associations were observed regardless of menopausal status, BMI, oral contraceptive use, or family cancer history. Blood type B was not associated with the risk of endometrial cancer in our study.


Discussion

Our results provide further evidence that ABO blood type may be involved in Carcinogenesis. Our finding that women with blood type A had the highest risk for cancers is consistent with some previous studies[1][7],[9],[10], including a study on uterine cancer[10]; however, this result is inconsistent with several others[6],[8],[12] that indicated blood type B was linked to the highest risk of cancers.

Several potential mechanisms for the association of the ABO blood type with cancer risk have been proposed, including inflammation, immune surveillance for malignant cells, intercellular adhesion, and membrane signaling[12]. More importantly, blood group antigens are expressed not only on the surface of red blood cells but also on the surface of many other epithelial cells. Alterations in glycosyltransferase specificity may lead to differential expression of blood group antigens on epithelial cells and thus influence tumorigenesis[12]. For endometrial cancer, A, B, and/or H (the precursor of A and B antigens) antigens were reported to be detected in tumors, but no distinct localization of these antigens was observed in normal endometria. H antigen was particularly frequently detected in endometrial cancers[20]. This may help to explain the excess risk of cancer for women with non–O blood types compared to women with blood type O, but it cannot explain the specific role of blood type A. Hence, whether and how antigens A and B function in different ways remains unclear. Interestingly, in this study, the cancer risk increased with increasing level of antigen A, though the number of women with homozygous blood type A in this population was unknown. The dose-response relationship strongly suggests the effect of antigen A in the development of endometrial cancer among Chinese women.

Strengths of this study include the population-based case-control study design, a large sample size, and a relatively high participation rate (82.7% for cases and 74.4% for controls). However, the blood types were self-reported in this study, and there were 363 participants unaware of their blood type. This raised our concern on recall bias and possible selection bias. In this study, the distribution of ABO blood types among controls was significantly different from that obtained from blood donors in Shanghai[18], but did not differ from that in controls of SBCS. Considering that the blood donors were not a randomized sample of general population and no significant difference in distribution of ABO blood types was observed between breast cancer cases and controls in SBCS (P for χ2 test = 0.19), it is unlikely that our positive results were caused by selection bias. In addition, although age, use of hormone replacement therapy, and use of oral contraceptives differed among the four blood groups in controls, the association of ABO blood types with cancer risk remained unchanged after adjusting for these factors and was consistently observed in subgroups stratified by these factors.

In summary, our study lends further support to the hypothesis that ABO blood type may be a marker of cancer susceptibility. The mechanisms underlying the moderate discrepancy in blood type–cancer associations for different cancers warrant further research.


This work was supported by United States Public Health Service (USPHS) grant R01CA92585 from the National Cancer Institute.


References
1. Aird I,Bentall HH,Roberts JA. A relationship between cancer of stomach and the ABO blood groups [J]Br Med JYear: 19531481479980113032504
2. Hoskins LC,Loux HA,Britten A,et al. Distribution of ABO blood groups in patients with pernicious anemia, gastric carcinoma and gastric carcinoma associated with pernicious anemia [J]N Engl J MedYear: 1965273126336375826425
3. Annese V,Minervini M,Gabbrielli A,et al. ABO blood groups and cancer of the pancreas [J]Int J PancreatolYear: 19906281882230362
4. Pandey M,Gautam A,Shukla VK. ABO and Rh blood groups in patients with cholelithiasis and carcinoma of the gall bladder [J]Br Med JYear: 1995310699516397795450
5. Roots I,Drakoulis N,Ploch M,et al. Debrisoquine hydroxylation phenotype, acetylation phenotype, and ABO blood groups as genetic host factors of lung cancer risk [J]Klinische WochenschriftYear: 198866Suppl. 1187972846954
6. Giannopoulos A,Kostakopoulos A,Sofras F,et al. Relation of ABO and RH blood groups with renal cell carcinoma [J]Acta Urol BelgYear: 198553129313922206
7. Anderson DE,Haas C. Blood type A and familial breast cancer [J]CancerYear: 1984549184518496478419
8. Tryggvadottir L,Tulinius H,Robertson JM. Familial and sporadic breast cancer cases in Iceland: a comparison related to ABO blood groups and risk of bilateral breast cancer [J]Int J CancerYear: 19884244995013170024
9. Henderson J,Seagroatt V,Goldacre M. Ovarian cancer and ABO blood groups [J]J Epidemiol Community HealthYear: 19934742872898228763
10. Janus ZL,Bailar JC 3rd,Eisenberg H. Blood group and uterine cancer [J]Am J EpidemiolYear: 19678635695785599933
11. Amundadottir L,Kraft P,Stolzenberg-Solomon RZ,et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer [J]Nat GenetYear: 200941998699019648918
12. Wolpin BM,Chan AT,Hartge P,et al. ABO blood group and the risk of pancreatic cancer [J]J Natl Cancer InstYear: 2009101642443119276450
13. Wolpin BM,Kraft P,Gross M,et al. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium [J]Cancer ResYear: 20107031015102320103627
14. Edgren G,Hjalgrim H,Rostgaard K,et al. Risk of gastric cancer and peptic ulcers in relation to ABO blood type: a cohort study [J]Am J EpidemiolYear: 2010172111280128520937632
15. Gates MA,Xu M,Chen WY,et al. ABO blood group and breast cancer incidence and survival [J]Int J CancerYear: 2011Month: 6 Day: 1 10.1002/ijc.26220 [Epub ahead of print].
16. Xie J,Qureshi AA,Li Y,et al. ABO blood group and incidence of skin cancer [J]PLoS OneYear: 201058e1197220694147
17. Xu WH,Dai Q,Xiang YB,et al. Nutritional factors in relation to endometrial cancer: a report from a population-based case-control study in Shanghai, China [J]Int J CancerYear: 200712081776178117230528
18. Xiang D,Liu X,Guo ZH,et al. Distribution of ABO blood types among Chinese population in Shanghai [J]Chin J Blood TransfusionYear: 20061912526 [in Chinese].
19. Fair AM,Dai Q,Shu XO,et al. Energy balance, insulin resistance biomarkers, and breast cancer risk [J]Cancer Detect PrevYear: 200731321421917646056
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Tables
[TableWrap ID: cjc-30-11-766-t01] Table 1.  Comparison of endometrial cancer cases and controls on demographic characteristics and selected risk factors, Shanghai Endometrial Cancer Study, 1997–2003
Factor Cases (n = 1204) Controls (n = 1212) P
Median age (25th, 75th percentile) 54.3(48.5, 62.1) 54.5(48.5, 62.6) 0.77
Education level (%)
 No formal education 7.9 11.0
 Elementary 14.1 13.0
 Junior high school 37.0 36.4
 High school 25.8 26.9
 Post-high school/College 15.1 12.8 0.05
Physical activity in METs (mean ± SD) 10.5±7.3 11.0±4.6 0.05
Oral contraceptive use (%) 18.5 24.9 <0.01
Cancer history among first-degree relatives (%) 35.2 27.9 <0.01
Nulliparous (%) 7.4 3.6 <0.01
No. of pregnancies (mean ± SD) 2.6±1.5 2.9±1.5 <0.01
BMI (kg/m2) (mean ± SD) 25.7±4.2 23.8±3.5 <0.01
Alcohol consumption (%) 2.8 5.4 <0.01
History of diabetes (%) 15.3 6.9 <0.01
Time of menstruation (years, mean ± SD) 32.8±4.9 30.6±5.4 <0.01
Menopause (%) 58.3 63.1 0.01
Use of HRT (%) 4.4 4.0 0.66

nt101MET, metabolic equivalent; SD, standard deviation; BMI, body mass index; HRT, hormone replacement therapy. Missing values have been excluded. P value for t test (continuous variables) or χ2 test (categorical variables).


[TableWrap ID: cjc-30-11-766-t02] Table 2.  Comparison of self-reported ABO blood type frequency among control participants with that among blood donors and the controls of Shanghai Breast Cancer Study (SBCS)
Blood type Number of subjects (%)
Controls In this study Blood donorsa Controls in SBCS
A 252 (25.7) 507 (29.9) 343 (27.8)
B 252 (25.7) 485 (28.6) 323 (26.2)
O 358 (36.6) 517 (30.5) 417 (33.8)
AB 117 (12.0) 186(11.0) 152 (12.3)

nt102aData from reference [18]. P1 = 0.002 for comparison between controls in this study and blood donors; P2 = 0.34 for comparison between two control groups.


[TableWrap ID: cjc-30-11-766-t03] Table 3.  Characteristics by self-reported ABO blood type among control participants, Shanghai Endometrial Cancer Study, 1997–2003
Characteristic ABO blood type
P
O (n = 358) B (n = 252) AB (n = 117) A (n = 252)
Median age (25th, 75th percentile) 55.1(49.4, 63.4) 54.1(48.7, 60.2) 54.3(49.0, 62.1) 53.5(48.0, 60.9) 0.04
Education of college or above (%) 25.5 30.3 31.9 28.8 0.45
Postmenopausal status (%) 66.8 61.5 65.8 58.7 0.19
Time of menstruation (years, mean ± SD) 30.8±5.5 31.3±4.4 31.3±4.7 30.1± 6.0 0.22
No. of pregnancies (mean ± SD) 2.9±1.4 2.6±1.3 2.9±1.3 2.7±1.3 0.09
Family history of cancer (%) 25.5 30.3 31.9 28.8
History of diabetes (%) 8.1 6.4 4.3 7.5
Use of HRT (%) 3.4 2.8 5.1 7.5
Use of oral contraceptives (%) 29.1 25.4 16.2 24.6
Cigarette smoking (%) 2.5 2.0 5.1 4.8
Alcohol drinking (%) 5.3 4.0 8.6 5.6
BMI (mean ± SD) 23.7±3.5 24.2±3.4 23.7±3.4 23.7±3.6

nt103P value for ANOVA test (continuous variables) or χ2 test (categorical variables).


[TableWrap ID: cjc-30-11-766-t04] Table 4.  Association of blood type with endometrial cancer risk, Shanghai Endometrial Cancer Study, 1997–2003a
Characteristic Blood type
P
A B AB A
All subjects
 Cases/controls 323/358 265/252 126/117 355/252 Px2 = 0.001
  OR (95% CI)
   Age-adjusted 1.00 1.17(0.93–1.47) 1.19(0.89–1.60) 1.56(1.25–1.95) Ptrend < 0.0001
   Fully adjustedb 1.00 1.00(0.79–1.28) 1.24(0.90–1.69) 1.50(1.19–1.90) Ptrend = 0.0003
Menopausal status
 Premenopausal women
  Cases/controls 125/119 113/97 62/40 148/104 Px2 = 0.24
   OR (95% CI)
    Age-adjusted 1.00 1.10(0.76–1.59) 1.53(0.95–2.45) 1.36(0.95–1.94) Ptrend = 0.05
    Fully adjustedc 1.00 0.96(0.64–1.44) 1.75(1.04–2.93) 1.39(0.94–2.06) Ptrend = 0.03
 Postmenopausal women
  Cases/controls 198/239 152/155 64/77 207/148 Px2 = 0.0019
   OR (95% CI)
    Age-adjusted 1.00 1.19(0.89–1.59) 1.00(0.69–1.47) 1.69(1.27–2.24) Ptrend = 0.0007
    Fully adjustedc 1.00 1.02(0.75–1.39) 0.99(0.66–1.48) 1.64(1.21–2.22) Ptrend = 0.0019
Body mass index
 BMI<25
  Cases/controls 161/243 107/154 62/78 185/169 Px2 = 0.0037
   OR (95% CI)
    Age-adjusted 1.00 1.05(0.76–1.44) 1.19(0.81–1.76) 1.65(1.24–2.20) Ptrend = 0.0005
    Fully adjustedc 1.00 0.99(0.71–1.37) 1.23(0.82–1.85) 1.62(1.20–2.19) Ptrend = 0.0009
 BMI ≥= 25
  Cases/controls 157/115 158/98 64/39 167/81 Px2 = 0.16
   OR (95% CI)
    Age-adjusted 1.00 1.15(0.81–1.63) 1.20(0.76–1.92) 1.47(1.03–2.11) Ptrend = 0.04
    Fully adjustedc 1.00 1.05(0.73–1.52) 1.11(0.68–1.82) 1.41(0.96–2.07) Ptrend = 0.08
Oral contraceptive use
 Never
  Cases/controls 256/254 212/188 105/98 298/190 Px2 = 0.0041
   OR (95% CI)
    Age-adjusted 1.00 1.12(0.86–1.46) 1.07(0.77–1.49) 1.57(1.22–2.01) Ptrend = 0.0008
    Fully adjustedc 1.00 0.97(0.73–1.29) 1.11(0.79–1.57) 1.49(1.14–1.95) Ptrend = 0.0022
 Ever
  Cases/controls 67/104 53/64 21/19 57/62 Px2 = 0.31
   OR (95% CI)
    Age-adjusted 1.00 1.15(0.71–1.88) 1.62(0.80–3.30) 1.29(0.80–2.10) Ptrend = 0.23
    Fully adjustedc 1.00 1.08(0.63–1.83) 2.00(0.91–4.37) 1.47(0.86–2.50) Ptrend = 0.09
Family history of cancer
 Yes
  Cases/controls 114/90 94/76 36/37 127/72 Px2 = 0.12
   OR (95% CI)
    Age-adjusted 1.00 0.98(0.65–1.47) 0.76(0.45–1.31) 1.40(0.94–2.08) Ptrend = 0.14
    Fully adjustedc 1.00 0.90(0.58–1.40) 0.82(0.46–1.46) 1.44(0.93–2.23) Ptrend = 0.11
 No
  Cases/controls 207/263 170/175 89/79 225/178 Px2 = 0.0051
   OR (95% CI)
    Age-adjusted 1.00 1.24(0.94–1.64) 1.44(1.01–2.05) 1.61(1.23–2.11) Ptrend = 0.0004
    Fully adjustedc 1.00 1.08(0.80–1.46) 1.56(1.07–2.29) 1.53(1.15–2.05) Ptrend = 0.0012

nt104aA total of 363 missing values were excluded from the analysis. bAdjusted for age, education level, menopausal status, time of menstruation, number of pregnancies, oral contraceptive use, hormone replacement therapy, cigarette smoking, alcohol drinking, family history of cancer, diagnosis of diabetes, and body mass index. cSimilar to b but excluding the corresponding stratified variable.



Article Categories:
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Keywords: ABO blood type, endometrial cancer, case-control study.

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