Saturday, June 21, 2008

Premature Hairs , Ageing And Predisposition To Cancer

Journal of Clinical and Diagnostic Research. 2007Dec; 1(6):577-580
LETTER TO THE EDITOR
Premature Greying of Hairs, Premature Ageing and
Predisposition to Cancer in Jajjal, Punjab: A Preliminary
Observation

HALDER A
Sir,
Reproductive, developmental, and neoplastic
disorders due to occupational pesticide exposure
are an international issue [1],[2]. There has been
increasing anxiety following several media
reports concerning health-related problems such
as cancer, infertility, malformation, abortion,
developmental delay, etc. in Punjab, particularly
in Jajjal of Bathinda [3–6]. Punjab Pollution
Control Board and Post Graduate Institute of
Medical Education and Research, Chandigarh,
have reported through press a close association
between environmental pollution and cancer in
Jajjal [7],[8]. To assess the authenticity of above
reports this preliminary survey was carried out.
A preliminary survey was undertaken during a
documentary film production for Public Service
Broadcasting Trust on the issue of pesticides
(granted by the Ministry of Environment, India),
to assess the authenticity of reported health
effects, in particular reproductive and cancer, in
Jajjal village of Bathinda, Punjab. Observations
were gathered on reproductive and other health
effects, using both qualitative and quantitative
methods. The qualitative phase consisted of brief
interviews (volunteered to provide information)
in school, market, medical clinic, and club from
Dept. of Reproductive Biology, AIIMS, New Delhi, India
Corresponding author: Dr. Ashutosh Halder, Associate
Professor. Dept. of Reproductive Biology, All India Institute
of Medical Sciences, New Delhi-110029, India.
Tel.: 011-26593304 ext. 4211/09313309579 (m); fax: 011-
26588663; e-mail: ashutoshhalder@yahoo.co.in
Contributors and guarantor: AH planned, designed,
organised, coordinated and carried out the survey. He also
did data analysis, interpretation, and data drafting of the
article. He will act as the guarantor of the paper.
farmer, shop keeper, school teacher, alternative
medical personnel, student, and unemployed in
Bathinda (city and several villages) for any
noticeable medical disorder. In the quantitative
phase, data were obtained from randomly
selected 15 families (from both higher and lower
socioeconomic group for equal representation,
i.e. random stratified) consisting of 596
individuals, from Jajjal village (most severely
affected village). Information was obtained on
current age, gender, age at menarche, age at
puberty, infertility, time to pregnancy, sex
determination, family size, contraception,
abortion, malformation (particularly
cryptorchidism, hypospadius, and neural tube
defect), stillbirth, postnatal death, mental
deficiency, age of menopause, premature
greying of hairs (more than 50% greying of
scalp hairs before the age of 40 years),
premature ageing (more than 10 years older in
appearance than corresponding chronologic
age), cancer, hypertension, diabetes mellitus,
joint pain, and any other significant problem.
Information was also obtained on source of
drinking water. Survey was assisted by village
chief, school head master, and two local nongovernment
organisations. Consent (verbal) was
obtained for the use of data, including
photograph and video recording for academic
use and video documentary.
The age range of survey population was between
<1 and 92 years. There were 330 males and 266
females, i.e. overall sex ratio of 806 (i.e.
skewed). Premature greying of hairs [9] was
seen in 28 individuals (4.7%) of both sexes (23
males and five females) and as early as 10 years
of age ([Table/Fig 1A, B]). Premature ageing
was seen in 19 males (3.2%) ([Table/Fig 2]).
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Halder: Letter to the editor – health effects in Jajjal, Punjab
Journal of Clinical and Diagnostic Research. 2007Dec; 1(6):577-580
There were eight cases (four males: parotid,
larynx, stomach and multiple myeloma; four
females: breast, cervix in two, and bone) of
death due to cancer in last 10 years. There were
118 boys between 13 and 23 years of age and 15
failed to show puberty (voice change and
moustache; enlargement of external genitalia
also failed in four cases); however, growth spurt
was normal. There were 85 girls between the age
of 13 and 20 years. All except five girls had
started menstruation before completion of 15
years. There were seven cases of infertility, 10
cases of neonatal and infantile death (five males
(A)
(B)
[Table/Fig 1] Premature greying of hairs
in an 11-year-old boy (A) and a 12-year-old
girl (B).
,five female), four cases of mental subnormality,
five cases of diabetes mellitus, one
case of cryptorchidism, and one case of spina
bifida.
Excess of cryptorchidism, hypospadius,
congenital malformation (including neural tube
defect), spontaneous abortion, prenatal sex
selection, infertility, early menarche, and early
menopause were not observed in the preliminary
surveyed population.
[Table/Fig 2] Premature ageing in a 44-
year-old man (left). His 74-year-old uncle
(right) is provided for comparison.
Premature greying of hairs, premature ageing,
and increased cancer deaths were observed in
the survey. Greying of hairs was due to varying
degree of admixture of white and black hairs and
not uniformly white as seen with albinism.
Furthermore, there was no pigmentary change in
skin or eyes. Greying of hairs is under-reported,
as most affected individuals (adults) use hair dye
to prevent social stigma, discrimination, and
difficulties in marriages. Although greyness of
hair in the survey was not quantified, however, it
was obvious, noticeable, and appreciable. Most
of the observed cases (19/29) of premature
greying of hairs in the survey were from healthy
school-going children, as they were not aware of
discrimination later on. The perception of grey
hair derives in large part from the admixture of
pigmented and white hair in most cases;
however, in some individuals it was from
pigment dilution. It is possible that melanocytes
from grey and white hair follicles can be
induced to pigment in vitro [9]. Spontaneous repigmentation
was seen in one case following
migration from the village, thus indicating local
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Halder: Letter to the editor – health effects in Jajjal, Punjab
Journal of Clinical and Diagnostic Research. 2007Dec; 1(6):577-580
environmental factors as likely explanation. It is
also supported by appearance of grey hairs in
two sisters few years after marriage in the
village. Hair greying may be caused by defective
self-maintenance of melanocyte stem cells [10]
or reactive oxygen species-mediated damage to
nuclear and mitochondrial DNA or through the
exposure of environmental toxicants [10].
Ageing has a variety of definitions and
implications depending on one’s perspective;
thus, phenotypes include extremely diversified
clinico-pathological conditions [11]. In this
study, premature ageing was considered when an
individual was apparently looking more than 10
years older than the chronological age, mainly
based on greying of hairs, alopecia, skin
wrinkling, and overall appearance. As the nature
of the study was a preliminary survey no attempt
to examine biomarkers (glucose, insulin, ATP,
and reproductive hormones, in particular
dehydro-epiandrosterone sulphate, reactive
oxygen species, ß-galactosidase, etc.) or
radiologic markers (osteopenia/osteoporosis,
soft-tissue calcifications, etc.) or other markers
(atherosclerosis, hypogonadism, atrophy of
organs, etc.) of ageing were made. Premature
ageing (excluding genetic progeria syndromes)
commonly refers to the unnatural acceleration of
the natural ageing process primarily due to
damage (faulty genome maintenance) from sun
exposure, other environmental assaults
(radiation, chemical toxins, metal ions, free
radicals, hydrolysis, glycation, etc.) and an
unhealthy lifestyle. Premature ageing was not
expected before the survey. There are two major
theories of ageing, i.e. evolutionary and damage
based [12]. The former is natural selection and
favours a genetic composition. Second theory is
based on accumulated cellular damage over a
time and mainly environmental. Reactive
oxygen species (ROS), the by-products of
cellular metabolism, have long been regarded as
the principal intrinsic effector of cell damage
[13]. An emerging consensus is that ageing is a
consequence of macromolecular damage by
ROS, which oxidise lipids, proteins, and DNA,
with damage to the DNA leading to mutations
and chromosomal abnormalities [14]. In some
instances, this could irreversibly affect important
functions of the cell without causing cell death,
i.e. cell senescence. The p53 protein plays a vital
role in maintaining cell cycle (cell-cycle
inhibitors). A defective p53 protein leads to
increased cancer susceptibility, while higher
than normal levels contribute to premature
ageing [15], through apoptosis-mediated cell
death and/or cell senescence.
There were eight cases of cancer death in last 10
years. This gives a frequency of 134 cancer
deaths per lakh per year. This incidence is higher
than expected (~50 per annum per lakh)
[16],[17]. From a study [17] of house-to-house
survey in Bathinda, cancer prevalence was found
as 103 per lakh in Talwandi Sabo (107/85315)
and cancer deaths as 52 per lakh per year. The
same study [17] also reported higher level of
heavy metals (viz. arsenic, cadmium, chromium,
selenium, and mercury) and pesticides (viz.
heptachlor, ethion, and chlorpyrifos) in drinking
water, vegetables, and blood in the region.
Several reports have found association of cancer
with environmental pollution, viz. arsenic with
leukaemia, radiation with cancer of bone/softtissue/
blood/lymphoid tissue, and pesticide with
cancers of thyroid/breast/uterus/prostate/testis
/lymphoma/leukaemia [18],[19]. Lung cancer
was reported with exposure to silica, asbestos,
chromium, nickel, and radon [20]. Preliminary
survey supports reports of excess of cancer
deaths in Jajjal.
This preliminary survey finds, for the first time,
many unreported health effects in Jajjal. These
are premature greying of hairs and premature
ageing. Survey supports reports of excess of
cancer deaths. Genomic instability, cancer, and
accelerated ageing (premature ageing and
premature greying of hairs) are interrelated. All
these health effects can be explained by one
hypothesis, i.e. "derailed genomic integrity
following exogenous insult". A large-scale
epidemiological survey is warranted to validate
the findings and if so then study to find out
reason and prevention.
Acknowledgement
I would like to thank Mr. Sumit Khanna,
independent filmmaker, Mumbai, India, for
inviting and arranging facility for the survey in
Bathinda. I also would like to thank Mr.
Surinder Singh, Jt. Director, Khetivirasat
(NGO), and Mr. Umendra Dutt, Kheti Virasat
Mission (NGO), for assisting with the local
people. I acknowledge Ms. Raminderjeet Kaur,
PhD student, Human Biology, Panjabi
University, Patiala, Punjab, for language
interpretation during the survey. I am grateful to
Mr. T Heinemann (Journalist) and LL Cour
579
Halder: Letter to the editor – health effects in Jajjal, Punjab
Journal of Clinical and Diagnostic Research. 2007Dec; 1(6):577-580
(photographer) of Heinemann Medier,
Copenhagen, Denmark, for providing some
photographs.
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