Estrogen and ERα: Culprits in cervical cancer?

Chung, Sang-Hyuk; Franceschi, Silvia; Lambert, Paul F.

doi:10.1016/j.tem.2010.03.005

Cited by 170 publications

(166 citation statements)

References 58 publications

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“…Epidemiologic data on the association of full-term pregnancies and recent OC use with ICC risk, and the cessation of the increase in ICC incidence rates after menopause also suggest an involvement of high estrogen levels but do not allow to rule out an influence of progesterone or androgens (30). The 2 best correlates of high unopposed estrogen levels in postmenopausal women (i.e., overweight/ obesity (31) and the use of estrogen-only menopausal replacement therapy (32,33) have been little studied in respect to ICC, and their evaluation is severely confounded by intense screening in menopausal replacement therapy users (34).…”

Section: Discussionmentioning

confidence: 99%

Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

Rinaldi

Plummer

Biessy

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC).Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E 2 ); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E 2 were calculated from absolute concentrations of T, E 2 , and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression.Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile ¼ 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E 2 , fE 2, and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR ¼ 3.14; 95% CI, 1.21-9.37), whereas E 2 and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre-or postmenopausal women.Conclusions: Our findings suggest for the first time that T and possibly E 2 may be involved in the etiology of ICC.Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring. Cancer Epidemiol Biomarkers Prev; 20(12); 2532-40. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

Rinaldi

Plummer

Biessy

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…[83] Estrogen is responsible for the onset, persistence, and malignant transformation of cervical cells [84] by stimulating oncogenic expression of HPV's E6 and E7 proteins promoting viral proliferation [17] and driving cells through the cell cycle. [85] Additionally, ROS activates HPV [16] and its E6 protein can in turn cause production of more ROS and DNA damage.…”

Section: Discussionmentioning

confidence: 99%

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Godar

Gurov²,

Merrill

2017

JER

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Because we observed increasing incidences over time, advancing age, higher estrogen levels, decreasing UVB (290-315 nm) doses, or lower vitamin D3, and Human Papillomavirus hiding in immune-privileged sites of hair follicles play roles in melanoma, we wondered if the majority of cancers might have similar carcinogenic drivers. To investigate this possibility, we performed worldwide analysis of all sites but skin cancer over time , advancing age, and UVB doses for males and females with all skin types and ages (0-85+) and in five age groups using IARC data. To investigate Human Papillomavirus's role, we analyzed the incidences of breast, prostate, and colon cancers in a developed country with European ancestry (New Zealand) having high amounts of androgenic hair and a developing country with Asian ancestry (India) having low amounts of androgenic hair. To potentially add epidemiology to the already established role of estrogen in cancer, we analyzed males and females in various countries around the world using the incidence of breast cancer (> 70 yr.) as an established indicator of estrogen levels. The analysis reveals cancer incidences are steadily increasing over time in developed but not developing countries regardless of skin type. Only US white, but not black, breast, prostate, and colon cancer incidences in the oldest age group significantly decreased with increasing UVB dose suggesting a role for vitamin D3. The data suggests the carcinogenic drivers in many cancers are estrogen, increasing age (or reactive oxygen species), decreasing vitamin D3 levels, and persistence of Human Papillomavirus infection in immune-privileged sites.

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“…Estrogen plays a significant role in the maintenance and development of the hair follicle, [39] an immune privileged site for HPV to hide. [4] Evidence that estrogen synergizes with HPV is provided by cervical cancer, [40] showing that estrogen is responsible for the onset, persistence, and malignant transformation of cervical cells. [41] The mechanism involves estrogen stimulating oncogene expression of HPV E6 and E7 proteins and promoting viral proliferation.…”

Section: Discussionmentioning

confidence: 99%

“…[42] ROS synergizes with estrogen to cause cancer, [43] it activates HPV, [44] and HPV's E6 protein can in turn cause production of ROS and DNA damage. [45] The estrogen receptor alpha also plays an important role in this transformation process [40,46] and low levels of vitamin D 3 help promote cervical cancer. [47] This perfect storm for initiating and promoting cervical cancer probably also applies to other HPV-related cancers like CMM.…”

Section: Discussionmentioning

confidence: 99%

Cutaneous malignant melanoma incidences analyzed worldwide by skin type over advancing age of males and females: Evidence estrogen and androgenic hair are risk factors

Godar¹,

Subramanian

Merrill

2016

JER

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We previously analyzed cutaneous malignant melanoma (CMM) incidences worldwide by sex, age, and Fitzpatrick skin type over time and found only European-ancestry populations have exponential increasing incidences and about a 2-log increase in the risk between the youngest age groups (0-14 and 15-29 yr). We proposed the increasing incidence over time may be from the spread of Human Papilloma Virus (HPV) found in CMM biopsies, and that the 2-log incidence increase between the youngest age groups might be from developing androgenic hair. The increasing incidence with age may be from white hairs transmitting UV radiation to follicular melanocytes. Here we analyzed CMM incidences over the advancing age of males and females of every skin type (I-VI) worldwide. We found only European-ancestry females have a linear increase in their CMM risk while males of all races have a power function increase in their risk with advancing age. We propose the gradual loss of HPV-infected androgenic follicles with advancing age of only European-ancestry females during and after menopause significantly reduces their CMM risk compared to all males who do not have significant estrogen loss and consequent loss of androgenic hair with advancing age. All other races have females with significantly lower amounts of androgenic body hair so that its loss with advancing age is not significant. These results combined with those in the literature and our previous findings showing CMM has been increasing over time, suggests estrogen synergizes HPV infection of androgenic follicular melanocytes significantly increasing the risk for getting CMM.

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Estrogen and ERα: Culprits in cervical cancer?

Cited by 170 publications

References 58 publications

Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

Endogenous Sex Steroids and Risk of Cervical Carcinoma: Results from the EPIC Study

All sites but skin cancer incidences analyzed worldwide by sex, age, and skin type over time (1955-2007), advancing age, and UVB dose reveals important carcinogenic drivers

Cutaneous malignant melanoma incidences analyzed worldwide by skin type over advancing age of males and females: Evidence estrogen and androgenic hair are risk factors

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