DOI: https://doi.org/10.21203/rs.3.rs-122076/v1
Background: Early age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer (breast ca). Multiparity is related to an increased risk but multiple full-term pregnancies decrease the risk of breast cancers. This study aims to investigate the reproductive determinants of breast cancer among women in the West Bank of Palestine.
Methods: A structured questionnaire was used to collect data in a case-control study; 237 registered cases and 237 controls aged 40 years old or more. A multivariate analysis model was used to adjust for the association between women’s reproductive factors and breast ca risk. Adjusted odds ratio (AOR) and 95% confidence interval (95% CI) are reported. This study was approved by Al Quds University Ethical Research Committee and the Ministry of Health research unit. All women provided written informed consent.
Results: In the multivariate analysis, having menarche after 13 years of age, using oral contraceptives for more than two months, using hormone replacement therapy (HRT), and getting pregnant at an early age (≤18 years) significantly doubled the risk for breast ca. Women who used hormonal contraceptives were significantly associated with higher odds of having breast ca 6.37 compared to those who did not use them (p <0.05). Similarly, nulliparous women showed 6 times the odds of breast ca be compared with women with one or more children (p = 0.005). Also, the mother’s educational level; parental consanguinity marriage; and positive family history of breast ca be strong determinants for breast ca in this study.
Conclusions: This study provides clear evidence of the role of using oral contraceptives and hormonal replacement therapy on women's breasts ca. Therefore, reproductive hormones use, whether as a birth control tool or in therapy, must be rationalized. More in-depth investigations are needed to identify the protective role of having children and breastfeeding practices on breast ca protection. Special attention should be considered for the special social and cultural factors related to sexual and reproductive issues among women in Palestine
Breast cancer (breast ca) is the main common cause of cancer mortality among women in the world [1]. Breast cancer is a multi-factorial type of cancer. Being genetically predisposed or having a family history of first degree relative with breast ca was shown to increase the cancer incidence [2-6]. Also, parental marriage, which is marriage from a relative, was shown to increase the risk too [7,8]. Among women aged 40 years or more, breast ca is related to an increased risk [9,10]. Modifiable risk factors related to energy balance-such as obesity, physical inactivity, sedentary behavior, and poor dietary patterns were shown also to be related to breast cancer risk [6,11-15].
The effect of reproductive factors strongly supports a hormonal role in its aetiology [16-19]. Early age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer [20-23]. However, multiple full-term pregnancies and long-term breastfeeding decrease the risk of breast cancer [24-26]. Reproductive surgeries such as ovariectomy, tubal sterilization, and hysterectomy may also affect breast cancer risk by altering hormone levels before menopause or by modifying age at menopause [27,28]. Long-term use of hormone replacement therapy (HRT) [29], but apparently not long-term use of oral contraceptives (OC), was also related to increased risk of breast ca [30]. Moreover, it was noticed that time since last oral contraceptive use was associated with breast ca higher risk more than recent use [31].
Breast cancer is the most common and widely spread type of cancer in Palestine and ranks as the third cancer which causes death. It constitutes 17.8 of all cancer cases. The total of documented new cases till the end of 2017 were 503 new cases in the West Bank, while 327 new other cases were recorded in the Gaza Strip, with a rate of 33.1 new cases per 100,000 females annually [32]. Few studies have tackled the risk factors of breast ca in Palestine [2,33]. In Gaza, a study among women aged 18 to 60 years suggested that positive family history of breast ca, high body mass index, and some common diseases (hypertension, diabetes mellitus) maybe the epigenetic factors promoting the occurrence of breast ca [2]. Reproductive determinants of breast cancer among women in the southern region of the West Bank will be presented here. This study finding may help to clarify the interaction of these factors that play a role in the development of breast cancer among the Palestinian women.
Study context
The cancer burden in Palestine is expected to increase which poses a substantial challenge for the health-care system. The limited financial and infrastructural resources and the political uncertainty exacerbate the problem [34]. Cancer care; i.e. diagnosis and treatment, services are provided in four hospitals in the West Bank. However, isotope scans like PET-CT is not available and all cases are referred to Israeli hospitals. The shortage of specialized physicians and the availability of drugs, chemotherapy, and radiation therapy is still a challenge in providing proper care for cancer patients [35]. This study was conducted at the major governmental hospital; i.e. Beit-Jala Hospital, in the southern area. Beit-Jala Hospital has an oncology department and daycare clinic that offers daycare medical services for cancer patients in the middle and southern areas of the West Bank.
Aim
In this study, we aimed at exploring the various reproductive risk factors for breast cancer in the West Bank of Palestine.
Study design
This case-control study was conducted at Beit Jala Governmental Hospital in the West Bank of Palestine over the period 2016 to 2017.
Study cases and controls selection
On the basis of hospital chart number, the selected study cases were 237 women. Cases were randomly selected from those attending the daycare oncology department or the chemotherapy unit of Beit-Jala hospital. These cases were pathologically confirmed breast carcinoma and were aged 40 years more at the time of the interview.
To serve as comparable and representative group matched controls, 237 women of the same age distribution and geographic area were randomly recruited from the screening program for breast ca. This control was confirmed as free from breast ca and was never suspected of any previous neoplastic disease or any other cancer. Their medical records were checked to have a normal (BIRADS 1) mammography. Those referred by a physician for a suspected history of breast problems were excluded. Only a very low proportion (2%) of selected women (study cases and Controls) refused to participate in this study.
This study was approved by Al Quds University Ethical Review Committee. Written approval was obtained from the Ministry of Health to access the patients' records from the oncology department and cancer registry. All women provided a written informed consent.
Data collection
From cancer patients medical recorders, we retrieved information related to breast ca date of diagnosis, stage at diagnosis, type of cancer, and therapy strategy.
Trained female interviewers administered in-person structured questionnaire during the patient visit to the oncology department. Controls were contacted by a nurse from the mammography department and were invited to participate. In case a control refused to come to the clinic, the interview was conducted through a phone call.
The questionnaire included questions on: demographic and lifestyle factors; parental consanguinity marriage; contraceptive history; use of hormone therapy; menstrual history; pregnancy and breastfeeding history; medical history, including cancer and mammogram history, and family history of malignancy. Women were also asked whether they had undergone surgery that partially or totally removed one or both ovaries. Women were also asked whether they had undergone a hysterectomy or tubal sterilization and the approximate month and year of the procedure(s).
Statistical analysis
SPSS version 23 (IBM Corp., Chicago, IL, USA) was used for the data analysis. Bivariate and multivariate unconditional logistic regressions was used to assess the association of breast ca with independent variables. Crude and adjusted odds ratio (AOR) and its 95% confidence intervals (CIs) were calculated to determine the precision of the estimates. The level of significance used was 5%. The p-value < 0.05 indicated significance.
In total, 237 cases and 237 age-matched controls were included. The mean age of study was 54.6 (SD=10.9) years and was 54 (SD= 9.9) years for the controls ( p>0.05).
Most of the study cases were diagnosed at stage 2 and 3 of cancer (35%), (30%) respectively. Most of the study cases (83%) knew they had cancer after they noticed a mass and only 17% were diagnosed by screening. More than half of the study cases had ductal carcinoma (n=138, 58%); 19 women had lobular carcinoma (8%); 5 women had follicular carcinoma (2.1%), 4 had mixed type (ductal lobular, 1.7%), but 30% did not have a documented type in their files. Almost all cases had chemotherapy treatment (98%). About 83% of cases had undergone partial mastectomy and half of them undergo a full mastectomy. Furthermore, 75% of cases had surgery as the first-line treatment and didn‘t receive neo-adjuvant therapy.
Socio-demographic factors
Table 1 shows the socio-demographic characteristics for cases and controls. Study cases and controls had significantly different distributions for multiple characteristics such as educational level, home type, family size, and parental consanguinity but not for others (table 1). Study cases were more educated compared to controls (more than 10 years of education was 41% versus 24.5%, respectively). Controls had bigger size families compared to study cases (mean 6.35, SD 2.6 versus mean 5.61, SD 2.96, respectively) but were living in smaller residences compared to study cases. About 43% of cases married from a first-degree relative compared to 21% in controls.
Socio-demographic factors and their association with breast cancer
The odd ratios for the association between socio-demographic factors and breast ca were summarised in Table 2. The odds of breast ca were higher among women educated for more than 12 years of education compared to those less educated. The odds of breast ca were 3.87 times higher among women living in separate housed compared with those living in apartments (95% CI: 2.36-6.33, p =0.00). Women with no children were also having odds of 2.5 times more for breast ca compared to those having children. Interestingly, the odds of breast ca were 2.5 times among women married to first level cousin (consanguinity marriage) compared to those not related or married to a second degree relative (95% CI: 1.60-4.08, p=000).
Reproductive factors and their association with breast cancer
Women’s age of menarche was significantly higher among controls compared to study cases [mean 13.2 (SD=1.01) years versus 13.6 (SD=1.08) years in the study cases, T-test significance <0.001]. The odds of breast ca were 2.6 times higher among women with late menarche (≥ 13 years) compared with those who got their menarche earlier (< 13 years old) (95% CI: 1.44–4.69, p value=0.002) (table 3). But, more than half of both study cases and controls were postmenopausal women with no significant difference in the age of menopause between controls and study cases (mean 49.21 (SD=3.55) years versus 48.5 (SD=4.38) years, T-test significance>0.05].
The mean age of using OC in the controls was 29.28 years (SD=6.02) and was 28.91 years (SD=5.96) in the study cases (T-test significance >0.05), and stopping using OC was also not significantly different between the two groups [controls was 34.38 years (SD=6.61) and was 33.91 years (SD=7.68), T-test significance >0.05). Those women who used hormonal contraceptives and hormone replacement therapy (HRT) were significantly associated with higher odds of having breast ca by 2.09 (95% CI: 1.10-3.95, p <0.001), 6.37 (95% CI: 2.40-16.9, p = 0.002) respectively compared to those who did not use. Similarly, nulliparous women showed 6 times the odds of breast ca (95% CI: 1.71-20, p = 0.005), compared with women with one or more children. Similarly, women who get pregnant at early ages (≤18 years) were at higher risk for breast cancer compared to women who got pregnant later (>18 years) (AOR 2.09, CI: 1.30-6.55, p=0.01) (table 3). However, breastfeeding showed less odds for breast ca but it the association was not statistically significant (AOR 0.59, CI: 0.32-1.58), but the longer the breastfeeding duration the more the lower the odds for breast can was seen (table 3).
There is an international variation in incidence of breast ca whose reason remains unclear. These variations were seen between countries with high and low income. Many of the risk factors for breast ca have been investigated but still there is a need to examine these factors in the various nations.
In this study we examined a broad spectrum of risk factors for breast ca including the women’s reproductive factors. The reproductive risk factors for breast ca identified for Palestinian women are shown to be similar to those observed in other studies. This study provides clear evidence that late menarche poses additional risk for breast ca. Early marriage and having children early in life were shown to increase the odds of having breast ca, which is still very popular in the Palestinian community. The roles of using oral contraceptives and hormonal replacement therapy on women’s health were shown evidently. Therefore, there should be a rational use of hormone whether as a birth control tool or in therapy. Having children proved to be protective against breast ca, but since most married women in Palestine are shown to breastfeed their children, we could not show the breastfeeding as a protective factor from breast cancer among this study group. However, we can still emphases on the role of breastfeeding on breast ca protection. Therefore, more in-depth investigations are needed to identify the relation of various factors especially of the protective role of having children and breastfeeding practices on breast ca protection in Palestine. Special attention should be considered for the special social and cultural factors related to sexual and reproductive issues among women in Palestine.
Several studies reported that women in the high socioeconomic status (SES) are at risk for breast ca [36], with an overall estimation of 20% increased risk [37]. This positive association was clearer among Hispanic and Asian women [38], and not only for breast ca, but also for other cancers such as colon, ovary and melanoma cancers [39]. Our study found that breast ca was more common among more educated than in less educated ladies and among women having less family income compared with women with higher family income. In the Northern area of Palestine, a previous study showed that there was an increased risk for breast ca by 4 folds among highly educated women [33], which was also reported among Egyptian women [40]. However, among European women, a direct dose response relationship was seen between education level and postmenopausal breast ca incidence [41]. Considering type of living place in our results, it was found women living in an apartment had significantly less risk of getting breast ca when compared to those living in a separate home that are assumed to be from a higher SES. In the United States, a study showed a significant trend of higher incidence with increasing SES [36]. Other studies showed that the lower SES increased the risk of breast ca, as females had less awareness toward screening techniques and diagnosis [42]. Our results could have the explanation that women generally who have more family income are able to afford health insurance and is more willing to spend money on their health with better medical care access. Also, the increased awareness among educated in having a mammography screening test compared to less educated women is very clear in Palestine. It is worth mentioning that screening in Palestine is free of charge for all women over 40 years of age. Another possible explanation is that the more the woman is educated the later they get married, have late pregnancy age, practice less breastfeeding periods, and have a lower parity which are the characteristics of women from higher SES. Indeed, socio-economic inequalities could affect the time of diagnosis, survival or mortality due to cancer despite improved knowledge, reduction of risk factors for cancer, early diagnosis and treatment [43].
Consanguinity is becoming a very strong factor for many diseases such as cancers and other genetic diseases in many countries [8,44]. Our study showed that daughters of unrelated parents showed a decreased breast ca risk, whereas those with first degree relative parents had increased risk by 2.5 folds. Similar finding was reported in United Arab of Emirates (UAE) in which unrelated parents of the subjects decreased the risk to the half (RR=0.5, 95%CI: 0.27- 0.93)[8]. This genetic issue was investigated in a study conducted in Palestine, which showed a real genetic mutation among breast ca females who had related parents, but the study revealed that although the consanguinity rate is high in the Palestinian population, no significant difference exists between consanguinity in breast ca and controls, but the sample size was very low [45]. However, a study among Israeli Arabs who are Palestinian in origin, showed an increase in diabetes and duodenal ulcer [44]. Consanguineous practices in populations might affect the gene frequency in these populations, which could lead to a major effect on the carrier rate of such genes. Therefore, in countries with high consanguinity, the incidence of several diseases and syndromes should be monitored with caution. Although some studies showed that there is a trend of decreasing breast cancer incidence with an increasing consanguinity rate [46,47].
It is believed that up to 10% of breast ca cases in Western countries were due to genetic predisposition [5] with a threefold increase in the risk of breast ca among those with family history of breast ca [48]. The consistent increase in the risk was when the relative is a mother or a sister [49]. In our study, women with a family history of breast cancer had a 4 folds increased risk to have breast ca. In Qatar, a country with high consanguinity marriage, a study showed that consanguinity was lower in breast cancer patients than in Controls, but family history of breast cancer was significantly more often in breast cancer patients [50]. The relative risk of breast ca ranged from 1.5 to 3.6 in a pooled analysis depending on the relative degree, with the highest risk was reported among women who had a mother or a sister with breast ca [51]. Furthermore, women living in the Gaza Strip and who had a positive family history of breast ca showed an increased the risk for breast ca (OR=2.7, 95%CI: 1.04-7.20). Similar results were reported among Moroccan women (OR=11.15, 95%CI: 2.54-49) [52] and among Algerian women where the odds for breast cancer was 4 times among those with a family history of breast ca (95%CI: 2.22-7.77) [53]. These two factors, i.e. consanguinity and family history of breast cancer, might have a synergistic effect in such studies and the risk might be greater if combined in these women.
Early age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer [22-24]. Also, parity and age of marriage are amongst the most known extrinsic factors that modulate breast cancer risk. It is well documented that parity has a dual effect on breast cancer risk with an increased risk during 5 to 10 years after pregnancy, followed by a strong and life-long protective effect [18,54].
In several studies, older age at menarche was inversely associated with breast ca risk. The high risk groups were females with menarche before age of 12 years (OR 1.5) [55], or 11 years [5]. On the other hand, the protection was in females who had menarche after 14 years (OR=0.84, 95%CI: 0.65-1.09)[56]. Furthermore, it was found among 117 studies that breast ca risk was increased by a factor of 1.050 for every year younger at menarche [23], and a delay of 2 years at menarche had led to a 10% reduction in breast ca all around the world [22]. This protection applied for all cancer subtypes (OR=0.72) [57]. Older age at menarche in our study was shown to be associated with increased risk of breast ca. The risk was significantly increased by three folds by menarche at the age of 13 or more. Similar results were found among Moroccan women, where age at menarche of less than 13 was significantly associated with breast ca [52,52]. Also, in the North area of the West Bank, and estimated risk of 6.5 increased the risk for breast ca too[33]. The protective results of older age at menarche was explained by decreasing in the cumulative number of ovulatory cycles, which is negatively associated with the risk, so with younger age at menarche, and with older age at menopause, a female would have more cycles, and so increased risk [58,59]. Consistent to our findings, was a Chinese-Vietnamese study which showed a slight increase in the risk of breast ca with older age at menarche [60].
According to the Palestinian Center Bureau of Statistics (2016), the mean age for the first marriage was 19.8 years in the southern region of Palestine [61]. Consequently, many women might have their first pregnancy and first delivery at a young age (below age 18 years). Women with breast ca in our study had a mean age of marriage of 20.4 years (SD=5.44). Our multivariate results showed an inverse association between age at first marriage and age of first pregnancy with breast ca. We could not see a difference whether a women had her first child before age of 18 years or after. In contrast, a study in the North region of the West Bank showed that there was a 10% increase in the risk of breast ca when the first marriage was below 20 years of age [33]. Another study in Gaza Strip showed that women who had their first pregnancy after the age of 35 years had an significantly increased for breast cancer by 11 folds [2]. Our results may be different from these studies due to the inconsistency in the cutoff point. In addition, multi-parity was shown to be protective among Moroccan women [52].
Our results revealed no significant association between full term pregnancies and the risk of breast ca. However, number of full term pregnancies was negatively associated with BREAST CA risk in almost all studies, even in the western world. This result was consistent not only for one type, but all subtypes of breast ca, for pre and post-menopausal women [62]. The reduction in the risk ranged from 18% to 60% [25,56,63]. Even in the Northern region Palestine, a 50% decrease in the risk was reported among women with 4 full term pregnancies or more [64].
One of the well established protective factors against breast ca is breastfeeding [65]. In our results, almost all women who had children had practiced breastfeeding, but the protective effect in our analysis wasn’t in breastfeeding itself, but in its period. Previous studies found that breastfeeding itself was protective; A Saudi study reported that never having breastfed had doubled the risk (OR=1.89, 95%CI: 1.19-2.94) [66]. Furthermore, breastfeeding decreased the risk of having breast ca by almost 60% in an Israeli study in our region, (OR=0.39, 95%CI: 0.26-0.59) [67]. Similar result was reported in Morocco with a 35% risk reduction (OR=0.65, 95%CI: 0.55-0.78) [52]. Other results even in USA confirmed this association with 14% increased risk among women who had never breastfed, (RR=1.14, 95%CI: 0.17-1.38)[9] . Breastfeeding has been proposed to protect against breast ca through hormonal mechanisms that include postponing the resumption of ovulatory menstrual cycles after a pregnancy [68], reducing estrogen levels in the breast [69], and having fully differentiated breast tissue which is less susceptible to the hormones [70]. In addition, it has been proposed that breastfeeding also has a direct mechanical effect by which carcinogenic agents are excreted from the breast ductal tissue [25].
Upon examining period of breastfeeding, results of studies were inconsistent. A study that summarized findings from developed countries showed that for every year a woman breastfed, her risk of developing breast ca was reduced by 4.3% [71]. Similar results were reported in an American study for different age and ethnic groups [72]. In China, the risk was reduced to the half in those who breastfed more than 3 children compared to those who never lactated (OR=0.53, 95%CI: 0.27-1.04) [64]. An article review showed that OR was 1.37 for never breastfed compared to 16 months or more of breastfeeding [55]. In our study, a very clear inverse dose response relationship was found, with AOR=0.39 for the group of 9 years or more of breastfeeding, compared to never breastfed, with a decrease the risk by 25% to 30% for additional 3 years of breastfeeding. Among Palestinian women in the north, the risk for those who never breastfed was doubled compared to those who had lactated for 4 years or more [33]. It was found that the reduced risk was only for hormone negative disease[62]. On the contrary, no association was found between breastfeeding period and the risk of breast ca [24], either in developed or developing countries [71].
With regards to the use of hormonal contraceptive pills (OCP) and their association with breast Ca, our study showed that oral OCP past use for more than two months significantly doubled the risk for breast ca (AOR=2.22), but could not show the duration effect on the risk of using OCP on breast ca. Similar result were revealed among Jordanian females [73,74]. The regular use of OCPs in Jordanian women was shown to be associated with increased risk of breast cancer in (OR = 2.25, 95% CI 1.34-2.79; p = 0.002), while the duration of OCs use was not associated with the increased risk of breast cancer (p > 0.05) [74]. However, many studies found a slight increase in the risk [75]. Other studies reported that the increased risk was only for the next 10 years just after the last OCP use [31]. Some studies on the other hand, found a decreased risk among women but at least after 10 years of the last use of OCPs [76]. A study in Iran showed that long term OCP use (>/=10 years) (OR = 3.17, 95% CI: 1.27-7.95, P = 0.01) increase the risk for breast ca [77]. On the contrary, some studies showed a protective role of OCP from breast ca. A study in Central African Republic showed a decrease in the risk for breast ca (0.62) [78]. In Palestine, 54.8% of married women aged 15–49 years reported using contraception and 44.0% of women of reproductive age used modern contraceptives [79].
Hormone replacement therapy (HRT) was very strongly associated with risk of breast ca in our results (AOR=3.97). Similar results were reported among Saudi and Jordanian women, (OR=2.25, 95%CI: 1.65-3.08) [66,73]. A population based study in Korea showed that the risk of breast cancer in HRT users was 1.25 [95% CI, 1.22-1.29] compared with HRT nonusers, and as the duration of use increased the adjusted hazard ratio (HR) increased (adjusted HR for 2 to <5 years was 1.33 and was 1.72 for ≥ 5 years) [29]. In our study, 77% of women use the HRT for less than 5 years (mean 3 years, standard deviation 2.61 years) with no significant difference between the study cases and Controls. The increased risk among HRT users was shown in most studies. Martino et al. showed a 30% increase risk for breast ca in past users compared to 60% in current users, revealing a dose response relationship with duration of use [80]. Nevertheless, it was reported that HRT therapy using estrogen alone had reduced breast ca risk in young women but increased the risk in older women [81]. In our study women could not tell which type of HRT they used and the exact duration of its use.
Some limitations must be considered to explain the findings of this study. Firstly, the study was carried out on patients living in the south area in Palestine; therefore known risk factors may be different in the general population. Secondly, information (recall) bias from self-reporting of information of some variables; for example, age of menarche, age of menopause, breastfeeding practices, abortion experiences, and others. Also, women could not report which type of OCP and HRT they used and the duration of its use. Third, using women who came for screening of breast ca as controls introduced some selection bias in the study. However, the results and limitations of the study are very useful due to the fact they contribute to the ongoing research in the field of breast ca among Palestinian women. In addition, this study was conducted in an Arab developing country where changes in lifestyle can provide other important information about breast ca risk factors.
This is the first study epidemiological study in Palestine that investigated the risk for breast ca by women’s reproductive factors. Significant differences of breast ca were found between study cases and controls: age at puberty, use of OCP and HRT, null-parity, early marriage, early pregnancy and early delivery. All these factors with being from a family of history of breast cancer and married to a first cousin showed great risks for breast ca. In Palestine, most women do breastfeeding, so more in-depth investigations are needed to identify the protective role of having children and breastfeeding practices on breast ca protection. Moreover, the Palestinian community must be aware of the effect of early marriage and parental consanguinity on breast cancer risk. In addition, these results are very important in clinical practice. Women must be aware of the use of OCP and HRT on their health too. The use of reproductive hormone whether as a birth control tool or in therapy must be rationalized. We encourage having more studies on breast cancer that tackles the specific type of breast ca in all areas of Palestine and other unknown determinants. Special attention should be considered for the special social and cultural factors related to sexual and reproductive issues among women in Palestine
Ethics approval and consent to participate
This study was approved by Al Quds University Research Ethical Committee which is built on Helsinki declarations. Therefore, all study methods were performed in accordance with the Helsinki guidelines and regulations. Al Quds University Research Ethical regulations are built on Helsinki regulations
Written approval was obtained from the Ministry of Health to access the patients' records from the oncology department and cancer registry. All women provided a written informed consent.
Consent for publication
Will be sent upon acceptance to publish
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Competing interests:
The authors declare that they have no competing interests.
Funding
This study was funded by Al Quds University research funds
Authors' contributions
NS and IK designed the survey and developing the study tool. IK was responsible for data collection, data entry, and primary analysis. NS and IK participated in the study of advanced analysis and developing study tables. NS was responsible for writing the manuscript. All authors read and approved the final manuscript.
Acknowledgements
The authors wish to thank all participants for their willingness to participate and the Ministry of Health teams for facilitating this study implementation. Also, the authors wish to express their gratitude to Al Quds University for funding this research.
Authors details
Nuha El Sharif and Imtithal Khatib, AlQuds University-School of Public Health, Abu Dis Camps, Jerusalem, Occupied Palestinian Authority.
Table 1: Socio-demographic characteristic of study participants
Characteristics |
Controls N=237 |
Study cases =237 |
Chi square |
|
Frequency (%) |
Frequency (%) |
P-value |
||
Age groups (years) |
39-44 |
50 (21.1) |
50 (21.1) |
-- |
45-49 |
40 (16.9) |
40 (16.9) |
||
50-54 |
37 (15.6) |
37 (15.6) |
||
55-59 |
40 (16.9) |
40 (16.9) |
||
60-64 |
19 (8.0) |
19 (8.0) |
||
65-69 |
27 (11.4) |
27 (11.4) |
||
More than 70 |
24 (10.1) |
24 (10.1) |
||
Educational level (years) |
1-6 |
117 (49.3) |
81 (34.2) |
0.001 |
7-9 |
62 (26.2) |
59 (24.9) |
||
10-12 |
44 (18.6) |
49 (20.7) |
||
>12 |
14 (5.9) |
48 (20.2) |
||
Home type |
Separate house |
147 (62) |
198 (83.5) |
0.001 |
Apartment |
90 (38) |
39 (16.5) |
||
Family monthly income** |
Less than 1000 |
55 (23.2) |
78 (32.9) |
0.012 |
1000 to 2000 |
182 (76.8) |
159 (67.1) |
||
Working status |
Yes (now or then) |
23 (9.7) |
35 (14.8) |
0.09 |
No |
214 (90.3) |
202 (85.2) |
||
Period of work (years) |
Less than 15 |
15 (65.3) |
16 (45.7) |
0.31 |
15-30 |
7 (30.4) |
15 (42.9) |
||
More than 30 |
1 (4.3) |
4 (11.4) |
||
Marital status |
Single |
10 (4.2) |
19 (8.0) |
0.20 |
Married |
189 (79.7) |
185 (78.1) |
||
Divorced or widowed |
38 (16.1) |
33 (13.9) |
||
Parity |
No |
12 (5.1) |
36 (15.2) |
0.000 |
Yes |
225 (94.9) |
201 (84.8) |
||
Family size (persons) |
1-5 |
93 (39.2) |
108 (45.6) |
0.16 |
6 or more |
144 (60.8) |
129 (54.4) |
||
Parental consanguinity relation |
No Relation |
123 (51.9) |
100 (42.2) |
0.001 |
1st degree |
52 (21.9) |
102 (43.0) |
||
2nd degree |
62 (26.2) |
35 (14.8) |
*p-value was calculated by using Pearson’s chi square test
** NIS: new Israeli Shekels: 1000 NIS is about 300 dollars
Table 2: Socio-demographic factors and their association with breast cancer
Characteristics |
Controls N=237 |
Study cases N=237 |
Univariate analysis |
Multivariate analysis |
||||
Frequency (%) |
Frequency (%) |
OR |
95% CI L-U |
AOR |
95% CI L-U |
P value |
||
Educational level (years) |
1-6 |
117 (49.3) |
81 (34.2) |
0.20 |
0.10-0.39 |
0.14 |
0.07-0.30 |
.000 |
7-9 |
62 (26.2) |
59 (24.9) |
0.28 |
0.14-0.56 |
0.27 |
0.13-0.57 |
.001 |
|
10-12 |
44 (18.6) |
49 (20.7) |
0.33 |
0.16-0.67 |
0.32 |
0.14-0.69 |
.004 |
|
>12 |
14 (5.9) |
48 (20.2) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
|
Family monthly income (NIS)** |
Less than 1000 |
55 (23.2) |
78 (32.9) |
1.62 |
1.08-2.43 |
1.80 |
1.13-2.90 |
0.012 |
1000 to 2000 |
182 (76.8) |
159 (67.1) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
|
Home type |
Separate house |
147 (62) |
198 (83.5) |
3.1 |
2.02-4.79 |
3.87 |
2.36-6.33 |
.000 |
Apartment |
90 (38) |
39 (16.5) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
|
Parity |
Yes |
225 (94.9) |
201 (84.8) |
0.30 |
0.15-0.59 |
0.39 |
0.19-0.80 |
.010 |
NO |
12 (5.1) |
36 (15.2) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
|
Parental consanguinity relation |
2nd degree |
62 (26.2) |
35 (14.8) |
0.69 |
0.43-1.13 |
0.68 |
0.39-1.16 |
0.16 |
1st degree |
52 (21.9) |
102 (43.0) |
2.41 |
1.58-3.69 |
2.56 |
1.60-4.08 |
.000 |
|
No Relation |
123 (51.9) |
100 (42.2) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
Legend: L lower, U upper, COR crude odds ratio, AOR adjusted odds ratio, Ref reference, CI confidence interval
OR was calculated by using logistic regression, p-value < 0.05. NIS: new Israeli Shekels
Table 3: Reproductive factors and their association with breast cancer
characteristic |
Controls N= 237 |
Study cases N= 237 |
Univariate analysis |
Multivariate analysis |
|||||
Freq (%) |
Freq (%) |
P- value |
OR |
95% CI L-U |
AOR |
95% CI L-U |
P value |
||
Age at menarche * (years) |
≥13 |
179 (75.5) |
205 (86.5) |
0.002 |
2.07 |
1.29-3.34 |
2.6 |
1.44-4.69 |
.002 |
<13 |
58 (24.5) |
32 (13.5) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Ever OC use for ≥ 2 months* |
Yes |
25 (10.5%) |
47 (19.8%) |
0.005 |
2.09 |
1.24-3.52 |
2.09 |
1.10-3.95 |
0.01 |
No |
212 (89.5) |
190 (80.2) |
1.0 |
(Ref) |
|
|
|
||
Use of HRT* |
Yes |
8 (3.4) |
36 (15.2) |
00 |
5.13 |
2.33-11.2 |
6.37 |
2.40-16.9 |
0.002 |
No |
229 (96.6) |
201 (84.8) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Age at first marriage (years) ** |
≤18 |
124 (54.4) |
95 (43.6) |
0.02 |
1.54 |
1.06-2.24 |
1.48 |
1.01-2.16 |
0.042 |
>18 |
104 (45.6) |
123 (56.4) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Parity ** |
No |
12 (5.1) |
36 (15.2) |
0.00 |
3.36 |
1.71-6.63 |
5.90 |
1.71-20 |
0.005 |
Yes |
225 (94.9) |
201 (84.8) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Age at first pregnancy (years)† |
≤18 |
105 (46.5) |
63 (30.9) |
0.001 |
1.94 |
1.31-2.89 |
2.90 |
1.30-6.55 |
0.01 |
>18 |
121 (53.5) |
141 (69.1) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Age at first Delivery (years)† |
≤18 |
81 (36) |
54 (26.9) |
0.045 |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
>18 |
144 (64) |
147 (73.1) |
0.65 |
0.43-0.99 |
0.56 |
0.24-1.29 |
0.17 |
||
Number of full term pregnancies† |
>5 children |
177 (74.7) |
140 (59.1) |
0.001 |
1.61 |
1.04-2.49 |
1.35 |
0.85-2.14 |
0.20 |
1-4 children |
49 (20.7) |
64 (27) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Ever breastfeeding† |
Yes |
217 (95.2) |
187 (85.8) |
0.001 |
0.31 |
0.25-0.63 |
0.59 |
0.32-1.58 |
0.26 |
No |
11 (4.8) |
13 (12.4) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Age at first breastfeeding (years)† † |
≤18 |
77 (35.5) |
48 (25.7) |
0.034 |
1.59 |
1.04-2.45 |
1.17 |
0.73-1.86 |
0.51 |
>18 |
140 (64.5) |
139 (74.3) |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
||
Total breastfeeding durations (all children) (years) †† |
≤3 |
12 (5.5) |
28 (15) |
00 |
1.0 |
(Ref) |
1.0 |
(Ref) |
|
4-6 |
32 (15.2) |
58 (31) |
0.75 |
0.34-1.67 |
0.75 |
0.34-1.67 |
0.49 |
||
7-9 |
59 (27.0) |
48 (25.7) |
0.35 |
0.16-0.76 |
0.35 |
0.11-0.76 |
0.008 |
||
>9 |
113 (52.1) |
53 (28.3) |
0.20 |
0.09-0.43 |
0.21 |
0.06-0.45 |
0.000 |
Legend Hormone Replacement Therapy (HRT), Chi square p value
*Among all participating women
** Age of marriage and parity calculations were based on number of non single women
†Age at first pregnancy, at first delivery, and number of full pregnancy calculations were based on married women with children
†† Age of first breastfeeding and duration were calculated bases on the number of breastfeeding