|Year : 2014 | Volume
| Issue : 4 | Page : 600-603
Pedigree studies and evaluation of risk factors of breast cancer in Goa
NV Fernandes, S Pinto, P Dias, D Kolwalkar, T Chipkar
Department of Zoology, Director Chowgule's Human Genetic Research Lab, Smt. Parvatibai Chowgule College Gogol Margao, Goa, India
|Date of Web Publication||1-Feb-2016|
N V Fernandes
Department of Zoology, Director Chowgule's Human Genetic Research Lab, Smt. Parvatibai Chowgule College Gogol Margao, Goa
Source of Support: None, Conflict of Interest: None
Background: Incidence of breast cancer (BC) is increasing in most of the countries, including the areas which have had previously low rates. AIM: The aim of this prospective study was to analyze the pedigrees of the patients for detecting hereditary factor prevalence and to investigate the possible risk factors associated with BC in a sample population from Goa. Materials And Methods: A prospective analysis was performed for 95 BC patients between 2011 and 2012. For assessing the risk factors, a proforma was designed and the necessary data was collected by interview. The process of collecting family history for drawing the pedigree included interviewing the informant. Statistical Analysis Used: Online calculators of statistics were used for standard deviation at www.easycalculation.com and fishers test at www.graphpad.com. Results: High frequency of BC was revealed in the sample population from Goa. This could be attributed to the changes in reproductive patterns, physical inactivity and obesity, or general increase in BC awareness. Factors which did not influence the frequency of BC in the sample population include parity, oral contraceptives, alcohol consumption, occupation, exercise, and nutritional supplement. High incidence of family history of 168/1000 individuals was observed in the present study. Conclusions: Proper management of BC is possible after assessment of cumulative risk of BC in females by a thorough study of both environmental and genetic factors. Cumulative risk can be greatly reduced by controlling the environmental risk.
Keywords: Breast cancer, genetic factor, inheritance, risk factors
|How to cite this article:|
Fernandes N V, Pinto S, Dias P, Kolwalkar D, Chipkar T. Pedigree studies and evaluation of risk factors of breast cancer in Goa. Indian J Cancer 2014;51:600-3
| » Introduction|| |
Breast Cancer (BC) is the most frequent cancer in women worldwide with 1.05 million new cases reported every year, representing over 20% of all malignancies among females. Incidence of BC is increasing in most countries, including the areas which have had previously low rates.,, While the epidemiological studies for BC conducted in India largely focused on risk factors such as religion, age at menarche, menopause, and reproductive history, not much attention has been paid to the role of family history. In India, genetic predisposition is responsible for 5-10% of all BC cases. It is well known that the hereditary factors play a far greater role in women for the development of BC.,, Very little information is available on the studies of BC in Goa. Goa has an average of 1000 cancer patients every year, or 70 cases/lakh population, which is much higher than the national average of 50 cases/lakh. Therefore, understanding its pathogenesis, morphological features, and various risk-factors, including family history, holds a great promise for the treatment, early detection, and prevention of BC. Since not much data is available on the research of these factors in Goa, the present study was undertaken to analyze the pedigrees of the patients for detecting hereditary factor prevalence and to investigate the possible risk factors associated with BC in a sample population from Goa.
| » Materials and Methods|| |
The cases detected at or reported at a major tertiary care hospital in Goa were considered for the present study. The cases reported/detected represented sample population from all over Goa. A total of 95 females were detected with BC. Equal numbers of females without history of cancer were selected as the control group. For achieving the objectives of the study, a proforma was designed and the necessary data was collected by interview method. The factor studied included regionality, religion, age, food habits, lifestyle, family history of cancer, habit of exercising, and food supplement intake. Besides this, detailed information was also collected about general health problems, such as other cancers and heart disease, onset, and age at diagnosis. The process of collecting information included interview sessions for filling up the proforma. The process of collecting the family history used to draw the pedigrees included interviewing the informant. The patients were also asked general questions to get more details about their disease. This included the type of BC, stage, age of onset, age of detection, age of onset of menstrual cycle, age of menopause, and marital status. The information was noted by checking the diagnostic reports of the patients. Pedigrees were constructed for all the patients to evaluate the prevalence of hereditary factors in Goa. The information collected was tabulated and analyzed. Mean and standard deviation (SD) were computed for quantitative data analysis. The statistical significance of associations between the various qualitative parameters was evaluated through Fisher's exact test (two tail). Online calculators of statistics were used for standard deviation at www.easycalculation.com and fishers test at www.graphpad.com.
| » Results|| |
A total of 190 individuals were surveyed in this study and were divided into experimental and control groups. Sample population included 95 BC patients and 95 patients without history of BC (control). The mean age of the females studied was 47.9 ± 11.16 with variance of 124.5, but most of the cases (17.9%) were detected for the age group 36-40 years. In the present study, 54.71% of BC cases were detected by physical examination and 18.95% by mammography. The present study revealed high frequency of BC in the sample population from Goa. Factors noted to increase BC risk were regionality, early menarche, late menopause, very early marriages, very late marriages, delayed childbearing, nulliparity, unmarried females, vegetarian food habits, and breastfeeding for <6 months. Factors which did not influence the frequency of BC in the sample population included parity, oral contraceptives, alcohol consumption, occupation, exercise, and nutritional supplement. High incidence of family history of 168/1000 individuals was observed in the present study. Our study suggests that hereditary factor is the leading contributor to the increased BC frequency in the studied sample population from Goa.
Risk factors assessed
The present study revealed high frequency of BC amongst the Christian females, followed by Muslim and then Hindu females. However, the increase was statistically insignificant (P = 0.9). BC frequency was significantly higher (P = 0.005) in patients of non-goan origin. The mean age of the females studied was 47.9 ± 11.16. Majority of the BC cases were detected between the age 36-40 years [Figure 1]. Mode of detection was by physical examination in 54.72%, by mammogram in 18.95%, and by CT scan in 3.16%. The frequency of BC was higher in females of age group 46-50 years and 61-65 years. All the BCs were ductal in origin. Our data shows that BC incidence was higher in females undergoing early menarche (12-14 years) as compared to the control. However, the increase was found to be statistically insignificant (P = 1.0). The present study showed significantly higher frequency of BC (P = 0.05) in patients who underwent late menopause of +50 years [Figure 2] as compared to the control. Frequency of BC was significantly higher (P = 0.026)in females with early marriages between 16-20 years and late marriages between 31-35 years [Figure 3]. Also, the age of having the first child was seen to affect BC development. Significantly higher frequency (P = 0.0096)of BC was seen in females having very early as well as delayed childbearing [Figure 4]. BC frequency was significantly higher (P = 0.0096)in females who had their first child at the age of 16-20 years. Besides, the present study showed that the frequency of BC in unmarried and nulliparous females was significantly higher (P = 0.014). Our study indicates that the duration of breast feeding has an impact on the development of BC. Significantly high BC frequency (P = 0.05) was also seen in patients who breastfed their children for <6 months [Figure 5]. Food habits also influenced BC development, as our study revealed significantly higher frequency (P = 0.0001)of BCin females with vegetarian food habits.
The probable risk factors that were inconclusive from the present study include radiation exposure, occupation, exercise, nutritional supplements, number of children, and oral contraceptives [Figure 6].
Genetic factor was evident through family history, sibling history, and pedigree analysis. Family history was evident in 16/95 cases, giving a frequency of 16.84%. This gives a high incidence of 168/1000 individuals in the population. Pedigree analysis showed that there is a great influence of hereditary factor in increasing the frequency of BC in the studied population. One of the explanations for familial aspects of BC is germline mutation in BRCA1, BRCA2, p53, and other genes. Thus, the present study clearly implies the importance of taking an appropriate history for eliciting family information from the relatives. It is crucial to elicit detailed personal and family history extending back to at least three generations, checking the medical records including pathology reports. Also, wherever possible, it is better to complete an accurate pedigree and obtain family history information from both maternal and paternal side of a family.
| » Discussion|| |
The present study reveals high frequency of BC (16.84%) in the sample population from Goa. The population based cancer registry data from the various parts of the country revealed BC as the most common cancer among women in Delhi, Mumbai, Ahmedabad, Calcutta, and Trivandrum. In India, the incidence and mortality rates on account of BC have been rising. Increase in the frequency of BC in the sample population may be attributed to the changes in reproductive patterns, physical inactivity, lifestyle changes, and obesity. Awareness and screening activity may also be partially responsible for the rising incidence of BC in this population. Age of the cancer patient is an important factor for both occurrence and management of the disease. In the present study, the frequency of BC was higher in females of age group 46-50 and 61-65 years. The mean age of the females studied was 47.9 ± 11.16. The mean age of occurrence of BC in India reveals that the disease occurs a decade earlier, as compared to that in western countries, which is reported to be 61.0 years.,, Most of the BC cases were detected at the age of 36-40 years. Average age of the patients seen in the six hospital-based cancer registries in the National Cancer Registry Project (NCRP) network was found to range from 44.2 years in Dibrugarh to 49.6 years in Bangalore and Chennai registries. Similarly, the average age of BC patients has been reported to be 50-53 years in various population-based registries located in different parts of the country.14 Similar hospital based studies conducted at Delhi and Jaipur have also reported that the average age of BC cases are 46.8 and 47 years., Early age of detection in the present study may be because of the medical facilities available and due to greater general awareness amongst people. Considering the hereditary factor, BRCA1/2 gene mutations may be predominant in this population. The present study revealed high frequency of BC amongst the Christian females, followed by Muslim and then Hindu females. However, the increase was statistically insignificant (P = 0.9). In another study, analysis of data by major religious groups indicated that 87%, 7.7%, and 5.3% belonged to Hindus, Muslims, and Christian communities, respectively.In yet another study, high incidence of BC was observed in the Parsi community in Mumbai. The present study does not reveal religion specific predominance of BC. Higher incidence of BC among the non-goans in this study may be attributed to very early marriages and consanguinity amongst the non-goans. Our data shows that BC incidence was higher in females with early menarche of between 12-13 years. However, the difference was found to be statistically insignificant (P = 1.0). Our findings are in agreement with some previous studies., The present study indicated significantly higher frequency of BC (P = 0.05) in patients who underwent late menopause, at the age of ≥50 years. Thus, it can be postulated that females undergoing early menarche and late menopause may be at a higher risk of BC. This may be due to increased exposure to endogenous estrogens. Since BC is an oestrogen-dependent cancer, women who have early menopause and do not take any oestrogen supplementation will have reduced risk of developing BC in later life. Our study revealed that the frequency of BC was significantly higher in females who married at a very early age (16-20 years) or married late (31-35 years) (P = 0.026). Similarly, significantly higher frequency (P = 0.0096) of BC was observed in females having very early as well as delayed childbearing. Unmarried females, nulliparous females, and those who breastfed their children for <6 months showed significantly higherfrequency of BC (P = 0.014). Our studies support the studies that suggest the primary risk factors for BC to be lack of childbearing or breastfeeding. An Indian study indicated that single women compared to married women had 4-5 fold higher risk for development of BC for an age group of ≥40 years. The frequency of BC was significantly higher (P = 0.0001)in individuals with vegetarian food habits as compared to the control population in the present study. The link between diet and BC has been much debated, with research in the recent years implying the impact of diet and other behaviours on BC. Increased BC frequency in vegetarian individuals may be on account of high-fat diet, which has been stated be a risk factor of BC.
The probable risk factors that were inconclusive from the present study include radiation exposure (ER), hormonal problems (HP), exercise (EX), nutritional supplements (NT), number of children, and oral contraceptives (OC). According to a study, these factors are said to influence the risk for BC. This study found that women using birth control pills have a slightly greater risk of BC. A study also found, albeit not conclusive, that vitamin D is related to reduced risk of BC and disease prognosis. Therefore, the factors suggestive of increased risk of BC from the present study include early menarche along with late menopause, shorter breast feeding duration, nulliparity, early marriages, and positive family history.
Family history was the evident factor in 168/1000 individuals in the studied population. This reflects contribution of hereditary factor in increasing the BC frequency in the studied sample population. In cross-sectional studies of adult populations, 5-10% of women have a mother or sister with BC, and about twice as many have either a first-degree relative or a second-degree relative with BC., Risk also increases with the number of affected relatives and the age at diagnosis. BC is also a common feature of Li–Fraumeni syndrome due to TP53 mutations and of Cowden syndrome due to PTEN mutations. Other genetic syndromes that may include BC as an associated feature include heterozygous carriers of the ataxia telangiectasia (AT) gene and Peutz–Jeghers syndrome. One of the explanations for familial aspects of BC is germline mutation in BRCA1, BRCA2, p53, and other genes. These cellular genes, which comprise dominantly acting oncogenes and recessively acting tumour suppressor genes, have been shown to contribute to genetic predisposition to a variety of human cancers. BCs occurring in BRCA1 mutation carriers are more likely to be estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2/neu receptor-negative, and they have a basal phenotype. BRCA1 defect predisposes to early onset of the hereditary breast and ovarian cancer and are more likely to be high grade and of serous histopathology. Though it shows autosomal dominant mode of inheritance, not everyone with the predisposition will develop cancer because of incomplete penetrance and/or gender-restricted or gender-related expression. Penetrance estimates, based on mutation-positive families ascertained through population-based series of BC patients, have generally been lower than estimates based on families with multiple-affected individuals. Such observations are consistent with the hypothesis that the BC risk in carriers is modified by genetic factors.
With documentation of pedigrees, familial BC may constitute as high as one-third of the total incidence of BCs, and approximately one-forth of them fall into the subset of hereditary BC. Therefore, pedigree analysis and gene mutation studies will enable detection of the familial inheritance and assessment of the risk factor. Thus, in the absence of genetic studies (both pedigree and mutation analysis), there might be considerable underestimation of hereditary BCs. Further studies of genetic mutation analysis can confirm the predominance of BRCA1/BRCA2 gene in the sample population from Goa with larger sample size for longer duration.
| » Conclusion|| |
Therefore, we conclude that proper management of BC is possible after assessment of cumulative risk of BC in the females by a thorough study of both environmental factors as well as the genetic factors. Environmental risk factors should be added to the familial risk factor, to predict the potential risk factor in females with positive family history. However, this risk can be greatly reduced by controlling the environmental risk. Therefore, genetic counselling can be offered after assessing the cumulative risk factors and may be focussed on avoiding high-risk environmental factors.
For estimating the incidence of BCs and for proper management of BC, detailed study of the probable risk factors is essential along with genetic studies by pedigree constructions and gene mutation studies.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]