Risk Factors for Breast Cancer in the City of Douala: A Case Control Study

Background: The breast cancer is an abnormal proliferation of mammary gland cells. This condition as well as other cancers is globally increasing in the world. It is the most frequent malignancy of women in the world and is a public health problem. Generally in Africa and central Africa in particular, few studies have been realized in search of risk factors of breast cancer. It’s all in this optical we began the study to determine the risk factors of this disease in the city of Douala. Patients and Methods: We conducted a case-control study, gave retrospectives collect on five years and prospectives collect on seven months. The studied population was all women aged 18 years and above with breast cancer diagnostic on histological plan for cases; and women from 18 years or more with normal physical examination and mammography. We have done our research in three reference hospitals of the city of Douala and two laboratories of pathological anatomy. The data were collected at the search files and the patients where interviewed. The parameters studied were: socio-demographic profile, clinic and Para clinic parameters, and the histological type. Results: At the end of this study, breast cancer is predominantly on young women in the city of Douala with a middle age of 44.08 ± 2.6 years. The most significant risk factors were age, age of the first birth ≥ 30 years, age of the first sexual act ≤ 18 years, low economic level, tobacco, hormonal contraceptive, parity. Conclusion: Finally, the malignancy of the breast takes a primordial place within the feminine population of Douala with many risk factors likes causes. family history and (BRCA1 and 2); overweight and obesity; benign breast disease (atypical hyperplasia); ionizing radiation; alcohol; tobacco; professional (ethylene medical conditions and treatments (dioxin, diethyls-tilbestrol, benign thyroid and those of


Introduction
Breast cancer is the most common and deadly malignant tumor in women worldwide with 410,000 deaths recorded in 2002 [1]. It ranks first in most countries and represents 23% of female cancers and 10.9% of all human cancers in the world [2]. In women, breast cancer was the most frequently diagnosed cancer in all regions of the world, except in Eastern Africa where cervical cancer dominated [3]. About 1 in 8 women in the US are at risk of developing invasive breast cancer. Between 1999 and 2005, there was a steady decline in cancer cases, observed only in women aged 50 and above [4]. Between 2010-2014 more than one in 10 breast cancer cases were late diagnosed in England, Scotland and Northern Ireland [2]. In France, the latest national estimates are those for 2012 with around 49,000 new cases of invasive breast cancer, corresponding to an annual gross rate of 148.5 cases per 100,000 women [5]. Cumulative African incidence and death due to breast cancer are 34.5 and 17.2 per 100,000 females [6].
In Africa, regional variability in incidence has been mentioned by Togo, including 16% in Senegal, 10% in the Republic of South Africa and 4% in Kenya [7]. In North Africa, breast cancer is also the leading cancer for women and represents 14% to 42% of all female cancers; reason why the WHO considers this affection as a priority of public health in this region of the world [8]. Breast cancer is one of the leading causes of death from cancer in the least developed countries. This is partly because the changing lifestyles are causing an increase in the operation, but also because the clinical progress recorded against the disease does not benefit the women living in these regions [3]. Several factors can cause breast cancer, including advanced age, which is the main risk factor. The risk of developing breast cancer increases with age, and can reach women at very different ages [3].
Breast cancer is 7% higher per five year increment of oral contraceptive use and 14% higher per ten year increment [9]. Like other risk factors we have the reproduction; non-oral hormonal contraceptives, HRT; family history and genetic factors; genetic conditions (BRCA1 and 2); overweight and obesity; benign breast disease (atypical hyperplasia); ionizing radiation; alcohol; tobacco; professional exposures (ethylene oxide); medical conditions and treatments (dioxin, diethylstilbestrol, etc.); benign thyroid diseases and those of the breast [10].
In Cameroon, in 1992, breast cancer ranked second after cervical, skin and liver cancer [11]. In 2012 among the population of Yaoundé, breast cancer was the most common cancer in women with the brutal and age-standardized incidence rate of 25.89% and 35.25% respectively [12]. In 2015, breast cancer was the cancer of young women in Cameroon with an average age of 46.58 ± 15.72 years [13]. These Cameroonian studies show that this pathology has experienced a sharp increase in recent years (having gone from 2nd to 1st place in 10 years) [11] [12]. In low-income countries like ours, this pathology is generally diagnosed at advanced stages; and the risk factors and prognosis for this condition have not yet been addressed. This is the reason why we propose to study the risk factors of breast cancer in the city of Douala in order to propose a preventive strategy.

Patients and Methods
It was a case study with prospective and retrospective data collection. The study is carried out in three referral hospitals in the city of Douala. The study concerned all women aged 18 and over who had consulted in our study sites for the past five years, i.e. from January 1, 2012 to December 31, 2017 for the retrospective study and from November 25 to April 31, 2018 for the prospective study.
The study was carried out on all women aged 18 and over who responded to the call for screening campaigns, or those simply recruited from hospitals during con- Clinical and radiological parameters (inspection for asymmetry of the breast, with surface abnormality, breast ulceration, appearance of the breast in orange peel, granular, deviation or retraction of the nipple, deformation of the breast. Palpation for an irregular, often painless mass; presence of one or more lymph nodes. The expression in search of a bloody or transparent flow Depending on age the results of breast ultrasound or mammography).
The data previously collected on a file was transcribed digitally on computer by input, using XL stat software and Spss 22 23.0. We carried out in the foreground an analytical statistics in order to search the indicators with central tendency (average, mode) and the indicators with tendency of dispersion (standard deviation, variance); and frequency measurement was used to assess the level of the indicators. In the background we have a bi-varied, then multi-varied analysis in order to bring out the risk factors for breast cancer in the city of Douala.

Distribution by Age
In case group, the age of cases ranged from 25 -82 year with mean age of cases is 53.29 ± 12.71 years. In control group the mean age of the participants was 40.38 ± 12.20 years from 17 to 77 years.
304 cases of breast cancer were recruited during our study. The average age was 48.05 years ± 2.6 years with a minimum age of 18 and a maximum age of 80.
The modal class was [40 -49] corresponding to a population of 90 cases (29.6%) ( Figure 1). Table 1 shows that there is a significant association between socioeconomic level and breast cancer (P < 0.05). Women with a low socio-economic level were twice as likely to develop breast cancer as those with a medium and high socio-economic level (OR = 2.82; CI = [2.17 -3.66]). The age distribution was significant between cases and controls with 27.3% of cases and 49.3% of controls had an age < 50 years

Clinical Factors Associated with Breast Cancer 1) Medical and toxicological history
As shown in Table 2, there is a significant association between the high-fat diet and breast cancer (P < 0.05). Eating a diet high in fat increases the risk of developing breast cancer.  The distribution according to active smoking was significant between the cases and the controls, 7.2% of the cases and 1.8% of the controls did not smoke (P < 0.05). Compared with women who did not smoke, women who smoked were 4 times more likely to develop breast cancer (OR = 4.21; CI = [2.3 -7.71]). Passive smoking was significant between the cases and the controls, 58.4 of the cases and 34.4% of the controls were not exposed to tobacco smoke (P < 0.05). Compared to women who were not, women who were exposed to tobacco smoke were twice as likely to develop breast cancer (OR = 2.68; CI = [2.03 -3.70]). The distribution according to BMI was significant between cases and controls, (P < 0.05). Compared to women who were normal weight and those who were overweight, women who were obese were more likely to develop breast cancer (OR = 1.94; CI = [1.50 -2.82]).
2) Reproductive and sexual factors There is a statistically significant association between the age of first sexual intercourse and breast cancer (P < 0.05), as shown in Table 3. Women who had

Multivariate Regression
According to Table 4, patients with a low socio-economic level were twice as likely to develop breast cancer as those belonging to a medium and high so-

Discussion
A total of 1520 women were recruited; 304 cases and 1216 controls. The mean age was 48.05 ± 2.6 years for the cases and 42.87 ± 2.2 years for the controls.
Those mean ages were similar to the study done in Iran, (Cases: 41.24 ± 5.71 years and controls: 41.06 ± 5.81 years) [14]. Our study demonstrated that there is a significant association between age ≥ 50 and breast cancer (OR = 2.59; CI = [1.96 -3.41]), Compared to women younger than 50 years of age, women 50 years and older were twice as likely to develop breast cancer. Adjusted for other variables, age ≥ 50 years (ORa = 1.17 with CIa = [0.71 -1.94]). Indeed, cell growth and development leads to possibilities of damage or genetic mutation. It is from these errors that cancer cells are born in our organism and more precisely in our case in mammary gland cells. These cancer cells have the ability to grow and multiply over time. According to Kamińska et al., the aging process is the greatest risk factor for breast cancer [15]. A very interesting correlation can be observed between the age when neoplastic disease is diagnosed and the expression of the estrogen receptor found in the examined tumor tissue. Neoplasms showing estrogen receptor overexpression ER (+) are characterized by a frequency increasing with age as opposed to ER (-) tumors, which occur more frequently up to 50 years of age and then reach a plateau. This phenomenon explains an increased percentage of ER (+) tumors diagnosed in women after menopause [16]. But in our study, this association was not such significant in multivariate analysis. It seems that association of age ≥ 50 with risk of breast cancer is mostly due to other factors.
The prevalence of breast cancer was higher in patients with a low socio-economic level (59.5%). The majority of cases included in this social class were housewives with a workforce of 145 (82.39%) cases. The distribution by socioeconomic status has shown that there is a significant association between low socioeconomic level and breast cancer. Patients with a low socio-economic level were twice as likely to have breast cancer as those belonging to a medium and high socio-economic level. After adjustment to other variables in multivariate analysis, this association remains significant (ORa = 2.08 with CIa = [1.48 -2.92]). These results are contradictory with those carried out in Western countries. The study by Robert S et al. found that, women living in the highest socioeconomic communities had greater odds of having breast cancer than women living in the lowest SES communities (1.20; 95% confidence interval = 1.05 -1.37) [17].
Younger age at first full-term pregnancy has been known as a protective factor in the lifetime risk of developing breast cancer. A plausible explanation for the protection effect is due to the higher degree of terminal differentiation of mammary epithelial cells at first birth, which makes the epithelium able to metabolize carcinogens and repair DNA damage more efficiently [21]. The prevalence of smoking among patients was 55.26% (168), of which 7.2% for active smoking and 58.4% for passive smoking. We found a significant association between smoking and breast cancer, (P < 0.05). Compared to women who did not smoke, women who smoked were more likely to develop breast cancer (OR = 4.21; CI = [2.30 -7.71]) for active smoking and (OR = 2.68; CI = [2.03 -3.54]) for passive smoking. But when adjusted by other variables, only active smoking remained significant. Hanaoka et al. found that both active and passive smoking were associated with an increased risk of breast cancer among premenopausal women [22]. Henoui et al., Affirmed that women who smoked passively were 3.58 more likely to developed breast cancer [23]. Some authors shown that Breast cancer risk is 7% -13% higher in current smokers, and 6% -9% higher in former smokers, compared with never-smokers [24] [25] [26]. A meta-analysis found a significant interaction between smoking, N-acetyltransferase 2 (NAT2) genotype, and risk of breast cancer: higher pack-years were associated with an increased risk among women with the NAT2 slow genotype, but not among rapid acetylators [27].
According to our study, a significant association exists between the age at first sexual intercourse (sexarche) and breast cancer (P < 0.05). Women who had their first sexual intercourse before 18

Conclusion
Breast cancer can be considered as cancer of the young woman in the city of Douala (Cameroon), with an average age of 48.05 years ± 2.6 years. This study allowed us to find the risk factors for breast cancer in the city of Douala during the past five years, the most emphasized of which was the age at first delivery greater than 30 years with a frequency of 90.3%, low socio-economic level; age ≥ 50, hormonal contraception.