|Year : 2011 | Volume
| Issue : 3 | Page : 303-307
Association between reproductive factors and breast cancer in an urban set up at central India: A case-control study
R Lodha1, A Joshi2, D Paul3, KM Lodha4, N Nahar5, A Shrivastava6, VK Bhagat1, S Nandeshwar3
1 Department of Community Medicine, LN Medical College and Research Centre, Bhopal, India
2 Peoples College of Medical College and Research Centre, Bhopal, India
3 Department of Community Medicine, Gandhi Medical College, Bhopal, India
4 Department of Biochemistry, Gandhi Medical College, Bhopal, India
5 Department of Medicine, Gandhi Medical College, Bhopal, India
6 Population-Based Cancer Registry, Indian Council of Medical Research, Gandhi Medical College, Bhopal, India
|Date of Web Publication||14-Sep-2011|
Department of Community Medicine, LN Medical College and Research Centre, Bhopal
Source of Support: None, Conflict of Interest: None
Background: Epigenetic changes, geography and environmental factors do surpass the genetic factors in the development of breast cancer. This study investigates the association of reproductive factors with the breast cancer in this context. Objective: To detect the association of reproductive risk factors with breast cancer in an urban set up at central India. Study Design: Matched paired community-based case-control study. Materials and Methods: The study was conducted for a period of a year from October 2008 to August 2009 in Bhopal (MP). Demographic data and reproductive risk factor related information were collected using structured questionnaire. Data analysis was done by Epi-info and SPSS 16. Results: History of using oral contraceptive pills (OR = 3.02, 95% CI: 1.28-7.11), history of not having breastfeeding (OR = 3.62, 95% CI: 1.29-10.16) and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826) were associated significantly with the occurrence of breast cancer in multivariate analysis. Conclusions: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.
Keywords: Adjusted odd ratios, breast cancer, breastfeeding, oral contraceptive pills, reproductive
|How to cite this article:|
Lodha R, Joshi A, Paul D, Lodha K M, Nahar N, Shrivastava A, Bhagat V K, Nandeshwar S. Association between reproductive factors and breast cancer in an urban set up at central India: A case-control study. Indian J Cancer 2011;48:303-7
|How to cite this URL:|
Lodha R, Joshi A, Paul D, Lodha K M, Nahar N, Shrivastava A, Bhagat V K, Nandeshwar S. Association between reproductive factors and breast cancer in an urban set up at central India: A case-control study. Indian J Cancer [serial online] 2011 [cited 2015 Apr 1];48:303-7. Available from: http://www.indianjcancer.com/text.asp?2011/48/3/303/84928
| » Introduction|| |
Geographical variations in incidence and mortality rates of breast cancer suggest that the known risk factors for breast cancer may vary in different part of the world and that environmental factors are of greater importance than genetic factors.  Some studies find that menstrual and reproductive factors are associated with an increased risk of breast cancer because they may increase lifetime exposure to estrogen.  An interesting observation is the women having shorter menstrual cycles (i.e., <26 days) spend more time in the luteal phase, when estrogen and progesterone levels are high and when breast mitotic activity is at its peak, compared to women with longer cycle length.  Greater number of births and early age at first full-term birth (FFTB) are also found to be associated with breast cancer. , Changes in menstrual and reproductive patterns among women (i.e. early age at menarche and late age at first childbirth) may have contributed to the increase in breast cancer risk, particularly among younger women . This complex interplay of genetics and environment in genesis of breast cancer is being reflected by the rising trends of breast cancer incidences in spite of formulating several control strategies; may be due to some initiating and triggering events which are still to be understood for completion of the natural history of breast cancer. , Reproductive factors being an environmental factor and because of having a reasonably sound patho-physiologic rationale may influence the initiation and progression of breast cancer. Therefore this study was conducted to ascertain the association between reproductive factors and breast cancer.
| » Materials and Methods|| |
This matched paired case-control study was conducted at Bhopal urban agglomerate from October 2008 to August 2009. The case group was defined as the women suffering from breast cancer and registered between January 2006 and December 2008 at Population-Based Cancer Registry (PBCR), Department of Pathology, Gandhi Medical College, Bhopal. The addresses of such 465 patients were taken from the registry office and the investigators then visited their home for interview. Out of these 465 cases, 226 cases could be traced and from these 226 cases, 215 cases gave consent for the interview. The control women were recruited from the same locality as of cancer patients but without any history of breast problem or neoplastic diseases reported earlier. The ratio of case to control was kept at 1 : 1. Case and control were individually matched with age ( ± 2 year), religion and socioeconomic status. Socioeconomic status was determined by the modified Prasad classification which is based on per capita per month income of the family.  Operationally cut-off limit to detect early menarche was set on 12 years based on a study done at Madhya Pradesh (that reports that the age of menarche varies from 12 to 15 years) and another study that reports the mean age of menarche 13.16 ± 1.10 (to include the observations below 1SD as early menarche). , Similarly late menopause was considered as age more than 50 years and women were stratified into three groups after adopting the reported mean age of menopause 44.7 years.  The effect of age at first pregnancy on breast cancer was determined by dividing the patients and control into two group as per age more than or less than 25 years at the time of first conception based on previous study.  Informed consent was taken from the study subjects before the interview. Information was collected in regards with age and status of menarche, marital status, age of marriage, history of oral contraceptive pills, age at first pregnancy and parity, reported abortion, positive history and duration of breast feeding, age at menopause and family history of breast cancer through personal interviews of 215 case and 215 controls using a pre-tested structured questionnaire. Data entry and data analysis was done with the help of Epi-info and SPSS 16. Both bivariate and multivariate analyses were performed and adjusted odds ratios (by logistic regression analysis) were calculated.
| » Results|| |
Out of the 465 participants, we could trace the address of 226 (48.6%) breast cancer patients and 215 (46.2%) gave their consent for interview. The reasons for non-traceability were migration to other places (49/339, 20.50%), incomplete addresses (118/239, 49.37%), death (29/239, 12.13%), and non-specified reasons (43/239, 17.99%).
Cases were 51.06 ± 10.804 years old ranging from 28 to 78 years and controls were 50.98 ± 10.708 years old ranging from 28 to 78 years. [Table 1] and [Table 2] indicate the distribution of studied independent variables in case and control groups, adjusted odds ratios and related 95% confidence intervals.
|Table 1: Bivariate analysis of the selected reproductive factors distributions among case and control group|
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|Table 2: Multinomial logistic regression for variables found significant in univariate analysis showing adjusted odd ratios (ORs) with 95% confidence interval|
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Logistic regression showed that history of using OCP (P = 0.010), history of not having breast feeding (P 0= 0.014), and family history of breast cancer (P = 0.037) were found to be significantly associated from breast cancer; similarly adjusted odds ratios (AOR) for history of OCP (OR = 3.02, 95%CI: 1.28-7.11), history of not having breastfeeding (OR = 3.62, 95%CI: 1.29-10.16) and family history of breast cancer (OR = 3.98, 95%CI: 1.06-14.826) showed positive association with the occurrence of breast cancer.
| » Discussion|| |
Limited resources and treatment modalities, profound financial liabilities to both provider and patients and inequitable distribution of treatment center provide the prevention strategies (educational awareness about the risk factors and screening at risk population); an upper hand over treatment as a key intervention against breast cancer.  Thus to determine the risk factors and at risk population should be the kernel of control strategies. In this context, this study detected the independent significant association of status of breastfeeding, OCP consumption and positive family history with breast cancer.
Breastfeeding as a protective factor for breast cancer does have a sound biological plausibility. Various pathophysiological mechanisms which are been proposed such as decreased frequency and intensity of ovulation thus maintaining the consistent lower level of estrogen; mobilization of endogenous carcinogens from the ductal and lobular epithelial cell environment; and facilitating the excretion of organochlorides (xenoestrogens) having the same carcinogenic potentials as estrogen.  A study from Delhi reported the mean duration of the sum total breastfeeding for all children as 6.58 years in patients and 7.4 years in controls (OR=1.91; 95% CI, 1.17-3.13).  Similarly, another study from South India has come out that lack of breastfeeding is positively associated with breast cancer.  A multicentric trial observed that prolong breastfeeding is associated with reduction in breast cancer risk among reproductive age females.  A review from France concluded that protective effect of breastfeeding is more for the women having extended periods of breastfeeding, particularly in case of BRCA1 mutation (thus avoiding a negative epigenetic change).  This study does identify the significant protective effect of breastfeeding from breast cancer but a short duration of breastfeeding (<12 months) did not show a positive association with breast cancer. This discrepancy may be due to the fact that ascertaining the exact duration of breastfeeding is affected by a significant recall bias.
The controversial effects of oral contraceptives on breast cancer have been studied extensively. But currently there is conflicting epidemiological evidence regarding the role of oral pills in causation of breast cancer, so it is difficult to make a blanket statement.  For instance, several studies have found no significant association between history of oral contraceptive uses and breast cancer, ,, but other studies have shown diametrically opposite results. ,,, This study could not measure the relationship of breast cancer with duration, type, dosage, and pattern of OCP usage because most of the subjects did not know or could not recall the details.
The findings presented here show that positive family history of breast cancer is associated with higher risk for breast cancer This is in accordance with other research findings indicating that a positive family history of breast cancer is a strong risk factor for breast cancer at young age; ,, although another study reports that positive family history has a comparatively small effect on the absolute lifetime incidences and mortality from breast cancer.  This observed significant association of family history with breast carcinoma in this study coupled with another finding of protective effect of breastfeeding is been further supported by another prospective cohort study on parous premenopausal women stating the inverse association of incidences of breast cancer among ever breastfed women with a positive family history of breast cancer.  Various pathophysiological mechanism are been described to explain these hereditary breast cancer as inheritance of one mutant BRCA (tumor suppressor gene) allele and somatic mutation in another allele, mutation in CHEK-2 and P-53 gene; but even after the cumulative consideration of all these genes still causation of such two-third cases are left unexplained.  This inspires to collect more epidemiological macro-evidences in order to supplement a lucid molecular etiopathogenesis.
Due to case-control nature of the study, certain biases do arise in the study, such as non-traceability of the participants who might differ in socio-demographic profiles from their fellows. Another is recall bias, which was minimized by including only incident cases. Medical records were checked to confirm past history of benign breast diseases. Genetic mutations, nutritional factors, obesity, radiation exposure and environmental exposure could not be ascertained because of lack of facility. Selection bias and confounding bias was minimized by selecting controls from similar age group and socioeconomic groups.
Our study revealed roles for some modifiable determinants of breast cancer that can be focused by public health intervention in local setup. The women who have one or more of the following risk factors should take the special attention to risk of breast cancer: According to this study, public awareness should be increased regarding the role of OCP, protective effect of breast feeding, and positive family history of breast cancer.
| » Acknowledgements|| |
Dr. Neel Kamal Kapoor, Principle Investigator, PBCR, Bhopal. Dr. N. Ganesh Oncogeneticist and Head, Department of Research, Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal,.
| » References|| |
|1.||McPherson K, Steel CM, Dixon JM. Breast Cancer-epidemiology risk factors and genetics. BMJ 2000;321:624-8. |
|2.||Colditz GA. Epidemiology and prevention of breast cancer. Cancer Epidemiol Biomarkers Prev 2005;14:768-72. |
|3.||Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiol Rev 1993;15:36-47. |
|4.||Meshram II, Hiwarkar PA, Kulkarni PN. Reproductive risk factors for breast cancer: A case control study. Online J Health Allied Sci 2009;8:5. |
|5.||Consolidated Report of Population Based Cancer Registries 2001-2004. Bangalore: National Cancer Registry Programme. Indian Council of Medical Research; 2006, December. Available from: http://www.icmr.nic.in/ncrp/report_pop_2001-04/cancer_p_based.htm. |
|6.||Asch BB, Barcellos-Hoff MH. Epigenetics and breast cancer. J Mamary Gland Biol Neoplasia 2001;6:151-2. |
|7.||Parashar SS. Principle of Sociology in Health Care. In: Rajvir B, Vaidya R, Tilak R, editors. Text Book of Public Health and Community Medicine. 1 st ed. Pune: Department of Community Medicine, AFMC; 2009. |
|8.||Biswas RK, Kapoor AK. Age at menarche and menopause among Saharia women-A primitive tribe of Madhya Pradesh. Anthroplogist 2004;6:247-52. |
|9.||Deo DS, Gattarji CH. Age at menarche and associated factors. Indian J Pediatr 2004;71:565-6. |
|10.||Sivkami M ,Syamala TS. Menopause: An emerging issue in India. Econ Polit Wkly 2005;40:282-9. |
|11.||Ahmad M. Risk factors for breast cancer among women attending breast clinic in. University Malaya Medical Centre Kuala Lumpur. NCD Malaysia 2003;2:23-31. |
|12.||Nair MK, Verghese C, Swaminathan R. Cancer: Current scenario, intervention strategies and projections. New Delhi: Cancer resource Commission on Macroeconomics and Health WHO Country Office for India. Available from:. whoindia.org/.../Commision_on_Macroeconomic_and_Health_Bg_P2_Cancers_current_scenario.pdf. [Last cited on 2010 Dec 04]. |
|13.||Helewa M, Winnipeg MB, Lévesque PR, Provencher D. Breast cancer, pregnancy and breast feeding;SOCG clinical practice guidelines. Canada: Society of Obstetrician and Gynecologist of Canada; 2002. 8p.Report no;111pg2-4. |
|14.||Pakseresht S, Ingle GK, Bahadur AK, Ramteke VK, Singh MM, Garg S, et al. Risk factors with breast cancer among women in Delhi. Indian J Cancer 2009;46:132-8. Available from: http://www.indianjcancer.com/text.asp?2009/46/2/132/49151138. [Last cited on 2010 Aug 22]. |
|15.||Gajalakshmi V, Mathew A, Brennan P, Rajan B, Kanimozh V, Mathews A, et al. Breastfeeding and breast cancer risk in India: A multicenter case-control study. Int J Cancer 2009;125:662-5. |
|16.||Freund C, Mirabel L, Annane K, Mathelin C. [Breastfeeding and breast cancer]. Gynecol Obstet Fertil 2005;33:739-44. |
|17.||Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: Collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713-27. |
|18.||Reid RL. Hormonal contraception and breast cancer: Keeping perspective. J Obstet Gynaecol Can 2007;29:207-13. |
|19.||Marchbanks PA, McDonald JA, Wilson HG, Folger SG, Mandel MG, Daling JR, et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002;346:2025-32. |
|20.||Brinton LA, Hoover R, Szklo M, Fraumeni JF. Oral contraceptive and breast cancer. Int J Epidemiol 1982;11:316-22. |
|21.||Jick H, Walker AM, Watkins RN, D' Ewart DC, Hunter JR, Danford A, et al. Oral contraceptive and breast cancer. Am J Epidemiol 1980;112:577-85. |
|22.||Hankinson SE, Colditz GA, Manson JE, Willett WC, Hunter DJ, Stamper MJ, et al. A prospective study of oral contraceptive use and risk of breast cancer (nurses health study, United States). Cancer Causes Control 1997;8:65-72. |
|23.||Yavari P, Mosavizadeh M, Sadrol-Hefazi B, Mehrabi Y. Reproductive characteristics and the risk of breast cancer- a case-control study in Iran. Asian Pac J Cancer Prev 2005;6:370-5. |
|24.||Pharoah PD, Day NE, Duffy S, Easton DF, Ponder BA. Family history and the risk of breast cancer: A systematic review and meta-analysis. Int J Cancer 1997;71:800-9. |
|25.||Ebrahimi M, Vahdaninia M, Montazeri A. Risk factors for breast cancer in Iran: A case-control study . Breast Cancer Res 2002;4:R10. |
|26.||Okobia M, Bunker C, Zmuda J, Kammerer C, Vogel V, Uche E, et al. Case-control study of risk factors for breast cancer in Nigerian women. Int J Cancer 2006;119:2179-85. |
|27.||Breastfeeding protects against breast cancer. Orlando,Florida: Ivanhoe Broadcast News; 2007. Available from: http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=15970. [Last cited on 2011 Jan 7]. |
|28.||Lester SC. The Breast. In: Kumar V, Abbas A, Fausto N, editors. Robbins and Cotran Pathologic Basis of Diseases, 7 th ed. Philadelphia: Saunders Publishing; 2004. p. 1133-5. |
[Table 1], [Table 2]
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