
Why Is Cancer More Common in Men? - lc1234
http://harvardmagazine.com/2017/03/why-is-cancer-more-common-in-men
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EdSharkey
So is the second X chromosome in women supposed to be an exact copy of the
first or do they differ? That's fascinating to me all by itself, and more so
that some genes in the dupe can reinforce the first even though the rest of
the chromosome is suppressed.

EDIT: Ah, wikipedia explains that the two X chromosomes in a standard-issue
woman come from the mother and paternal grandmother, and then ... "Early in
embryonic development in females, one of the two X chromosomes is randomly and
permanently inactivated in nearly all somatic cells (cells other than egg and
sperm cells). This phenomenon is called X-inactivation or Lyonization, and
creates a Barr body. If X-inactivation in the somatic cell meant a complete
de-functionalizing of one of the X-chromosomes, it would ensure that females,
like males, had only one functional copy of the X chromosome in each somatic
cell. This was previously assumed to be the case. However, recent research
suggests that the Barr body may be more biologically active than was
previously supposed." Which must be related to the EXITS that the OP refers
to.

Being a male, I'm troubled by the fitness of the Y-chromosome over the
generations. It seems to me that it can only accumulate errors and mutations.
However, I suppose the same could be said about the mitochondria that come
exclusively from females. This partial double-X scheme seems like a useful way
of mixing up traits intrageneration and maybe strengthen healthful cell
behaviors.

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incongruity
_> It seems to me that it can only accumulate errors and mutations._

Except some of those mutations can be _useful_ – some deadly, but some could
be selected for as one's environment/niche shifts. That's evolution and
selection in a nutshell. Not all mutations are bad and not all bad mutations
are always bad.

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EdSharkey
Yes, truly over the long haul, the fittest survive - helpful mutations account
for all survival thus far.

I just envy what I interpret as an intragenerational bolstering of genetic
traits that females have, assuming the EXITS thing is truly what's going on.
They don't have to wait a generation to perhaps select out the bad, they get
to do it on the fly.

~~~
incongruity
It's a conservative strategy -change from one generation to another will
likely be moderated/averaged by the influence of the second X chromosome for
female offspring. Alternatively, single copy governed traits (as in males)
mean greater ability to adapt (at a higher mortality rate) and those
successful remaining males can propagate their single X chromosome (new and
improved, thank you) to their daughters. It's a cool pattern of balances,
IMHO.

~~~
EdSharkey
Hmm. Are you saying that men's imputing of adaptations to their one X
chromosome is somehow more concentrated/effectual than the adaptations a woman
imputes to her 2 X chromosomes? What is the mechanism and how did you draw
that conclusion? Because she only passes one along?

It seems to me that chiefly the non-suppressed X chromosome in females would
see action by its workings and thus accumulate adaptations.

~~~
echelon
Females have both X chromosomes active, but only one copy per cell due to Barr
body deactivation. Some female cells have one copy active, others utilize the
other copy.

This scheme can lessen certain X-linked genetic disorders in women since not
all cells will be affected.

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0xcde4c3db
Although the title seems more appropriate for a ponderous meditation on a
great mystery, the article is pretty concise and does cover the case for a
specific mechanism. I think the HTML title ("A reason why cancer is less
common in women") is better.

~~~
devishard
I agree, but only because questions so often go bad in titles that I now avoid
them on principle. This is a rare situation where the question asked in the
title is answered in a non-obvious way, so I can't actually point to anything
wrong with titling this with a question.

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aetherson
Does anyone know how the X-inactivation thing works with the popular
explanation for why women are less likely to be color-blind than men (ie: They
have two copies of the gene for sensitivity to light of that wavelength, so
both copies must be mutated in order to be insensitive)?

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skosuri
I'll take a hack:

1\. Imagine the retina as a field of neurons that are receptive to light.
Imagine different types of neurons are sensitive to different types of light
(RGB). Each person has two copies (or alleles) of the R, G, and B genes. The R
& G genes are on the X-chromosome.

2\. In a color-blind person, the R & G genes merge to form a R-G allele that
is sensitive to some red-green combination. Thus, men who carry this R-G gene
have cells that express B and R-G genes and thus are red-green colorblind
(they can't distiguish between the two because they only have one type of
receptor for the two). Remember they only have one copy of these R and G
genes.

3\. Women might carry the R-G allele, but in those cases their retina as a
whole display R, G, B, and R-G. These people are known as heterochromats can
can distinguish colors better than normal people. Note that X-inactivation
leads to cells even having R-G allele, or R or G gene.

4\. It's rare for a woman to have two R-G alleles. When they do, they are red-
green colorblind.

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tbihl
In (3), are you describing what I've sometimes heard called tetrachromat? Is
that now confidently considered extant? Last I'd heard, it was an exciting,
but only slightly substantiated, theory, but I'd love to see more about it!

~~~
skosuri
Yes, I think you are right. I thought I remember it being heterochromat, but
looking online all references seem to be to tetrachromat. In terms of
evidence, I think prevalence is there, but there were some papers where they
actually tested color perception differences (at least from wikipedia).

~~~
aetherson
Heterochromia iridum is the condition of having two irises of different
colors, you may have blurred the name of that condition with tetrachromacy.

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rokosbasilisk
More money is spent on preventing cancer in women in treatment, research, and
preventive medicine.

Google the history of the brca gene, research and tests around it. Its quite
amazing.I hope all cancer research gets the pipeline it got.

~~~
cauterized
The breast cancer movement was started because at the time, male-only cancers
(such as prostate and testicular cancers) were getting far more funding and
research, while breast cancer was essentially being ignored despite being at
least an order of magnitude more common.

That it's more common has probably made it easier to do research on once it
gained sufficient visibility and funding.

~~~
gman83
Breast cancer was not an order of magnitude more common than prostate cancer:

[http://onlinelibrary.wiley.com/doi/10.3322/caac.21332/full#c...](http://onlinelibrary.wiley.com/doi/10.3322/caac.21332/full#caac21332-fig-0003)

~~~
thebspatrol
Prostate cancer isn't as big of an issue fatality-wise.

Right now breast cancer has a disproportionate amount of money spent on it,
but I don't think comparing it to prostate cancer is fair.

~~~
daviddavis
_Prostate cancer isn 't as big of an issue fatality-wise._

Are you sure? It looks like they're both about 21 deaths per 100,000 people:

[https://seer.cancer.gov/statfacts/html/prost.html](https://seer.cancer.gov/statfacts/html/prost.html)

[https://seer.cancer.gov/statfacts/html/breast.html](https://seer.cancer.gov/statfacts/html/breast.html)

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dnautics
I immediately guessed that this would be the explanation before reading the
article. An important corollary hypothesis (that would exclude things like
androgen effects) would be to do a statistical analysis on XY-women and see if
they have similar cancer rates as men.

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stagbeetle
That is, if they can round up a representative sample. If the lack of Swyer
syndrome (XY-women) published works is telling of anything, it's that cases
are very rare.

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lsd5you
... and because men have more cells in their body and so more tickets for the
cancer lottery.

~~~
hydrogen18
If this increased cancer rates, whales should be completely consumed by cancer
at a young age.

However, there are few cases of whales being found to die of cancer.

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allendoerfer
Human men are pretty similar to human women, whales are kind of different. So
the number of cells alone is quite a good way to differentiate men and women,
not so much humans and whales.

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zo1
Then it's not about gender, other than the gender being a proxy for a skewing
of the "weight" of the individuals involved.

But, if the GP's hypothesis were to be empirically tested, I guess they could
correct for the weight or volume of the individuals being sampled.

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mtdewcmu
Here are a couple of other facts:

1\. Autoimmune diseases are more common in women

2\. The immune system kills tumor cells

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JPLeRouzic
Then Cancer should be more common in women, isn't?

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gozur88
The implication is womens' immune system is more trigger happy, which would
make cancer in women less common.

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stagbeetle
My first thought was that the opposite was true. The immune system attacks
healthy cells, increasing inflammation, thus stress. Thereby lowering the
normal immune system and allowing cancer cells to flourish.

Unless you're talking about all-encompassing diseases (I can't think of any
off the top of my head). Otherwise, I don't think Celiac/MS/Diabetes is
fighting any cancers.

~~~
gozur88
The problem is if your immune system is too permissive it's leaving around
damaged DNA lines that can later become even more damaged in a cancer kind of
way.

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jakubp
Hypothesis: it's socially more acceptable for men to not care for their body
as much as women do, eat worse, drink more soda and beer, etc. leading overall
to more sugar(y) foods and more inflammation?

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stagbeetle
Social conditioning and less general sensitivity, more like.

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jakubp
Social conditioning ~= socially more acceptable, would you agree?

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jankotek
Because men receive worse medical treatment. Just compare how prostate and
breast cancer are promoted. It also corresponds with other statistics like
life expectancy, medical expenses, disposable income...

~~~
voidlogic
>Because men receive worse medical treatment.

What about an alternative... Men are less likely to seek medical treatment?

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tajen
Are you suggesting men don't seek medical treatment therefore it's their fault
for getting sick?

Girls often don't _want_ to become programmers, and, as I know it, we don't
say "It's their fault". We just raise the issue and everyone is fighting to
make them want to become programmers.

It's way past time we apply the same reasoning to men's problems as women's
problems. Males not seeking medical treatment could be because they're not
aware of it (i.e. not enough funding for male diseases as female preventive
programs). Or it could be because males are more suicidal about life, because
they get the short end of the stick in pretty much all countries, despite the
way it is framed in statistics, and we should equally fight for that. In any
case, any statistics which leads to 6-year-shorter life expectancy denotes a
very acute problem, for which funding should be given in equal level as for
women's equality.

~~~
voidlogic
>Are you suggesting men don't seek medical treatment therefore it's their
fault for getting sick?

I made no attribution of fault... simply an alternative primary cause to the
person I responded to.

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Pilfer
I found a really excellent answer to this question in one of my university
evolution textbooks [1]. The fact that men generally die sooner than woman (in
humans) has been well studied and we've come to a fairly decent answer.

\--

Why do people die?

The answer to this mystery has been partially solved by senescence theory
(Williams, 1957). Senescence is not a specific disease, but rather the
deterioration of all bodily mechanisms as organisms grow older: Senescence
theory starts with an interesting observation: The power of natural selection
decreases dramatically with increasing age. To understand why this occurs,
consider a twenty-year-old woman and a fifty-year-old woman. Selection
operates far more intensely on the younger woman, since anything that happens
to her could affect most of her future reproductive years. A gene activated at
age twenty that weakened a woman’s immune system, for example, could damage
her entire reproductive capacity. If the same damaging gene became activated
in the fifty-year-old instead, it would have almost no impact on the woman’s
reproductive capacity. Selection operates only weakly on the older woman,
since most or all of her reproduction has already occurred (Nesse & Williams,
1994).

Williams (1957) took this observation as a starting point and developed a
pleiotropic theory of senescence. Pleiotropy is the phenomenon whereby a gene
can have two or more different effects. Let’s say that there is a gene that
boosts testosterone in men, causing them to be more successful in competing
with other men for status early in life, such as in their twenties and
thirties. But the elevated testosterone also has a negative effect later in
life— increasing the risk of prostate cancer. This pleiotropic gene can be
favored by selection-— that is, it increases in frequency in subsequent
generations—because the early advantage in status gains for men outweighs the
later cost in lowered survival due to prostate cancer. Through this
pleiotropic process, we have evolved a number of genes that help us early in
life but cause damaging effects later in life, when selection is weak or
absent.

The pleiotropic theory of senescence helps to explain not only why our organs
all wear out at roughly the same time late in life, but also why men die
younger than women— roughly seven years earlier on average (Kruger & Nesse,
2006; Williams & Nesse, 1991). The effects of selection operate more strongly
on men than on women because the reproductive variance of men is higher than
that of women. Stated differently, most fertile women reproduce, and the
maximum number of children they can have is sharply restricted— roughly
twelve, for all practical purposes. Men, in contrast, can produce dozens of
children or be shut out of reproduction entirely. Because men have greater
variability in reproduction, selection can operate more intensely on them than
on women. In particular, selection will favor genes that enable a man to
compete successfully for mates early in life to be one of the few who
reproduces a lot or to avoid being excluded entirely.

Selection for men’s success in mate competition will be favored, even if it
means that these genes have detrimental effects on survival later in life.
Even though men can and sometimes do reproduce for a longer period of time
than women. Senescence theory explains why these later reproductive events
will have a much smaller impact than events occurring earlier in life for men.
Genes will be selected for early success in mate competition more strongly in
men than in women, at the expense of genes that promote survival later. This
strong selection for early advantage produces a higher proportion of
pleiotropic genes that cause early death. As one researcher noted, “it seems
likely that males suffer higher mortality than do females because in the past
they have enjoyed higher potential reproductive success, and this has selected
for traits that are positively associated with high reproductive success but
at a cost of decreased survival” (Trivers. 1985, p. 314). Men, in short, are
“designed” to die sooner than women, and the theory of senescence helps to
solve the mystery of why.

In summary, selection is most potent early in life because any events that
happen early can affect the entire span of a person’s reproductive years. As
people get older, however, the power of selection weakens. In the extreme case
something that happened to you in old age right before you died would likely
have no effect on your reproductive capacity. This means that selection will
favor adaptations that give beneficial effects early in life, even if they
come with heavy costs later on. These heavy costs cumulate in old age,
resulting in the deterioration of all body parts at roughly the same time. In
this sense organisms can be said to be “designed” to die.

\--

The authors are pushing the X-linked recessive inheritance hypothesis
[https://en.wikipedia.org/wiki/X-linked_recessive_inheritance](https://en.wikipedia.org/wiki/X-linked_recessive_inheritance)
, which by itself is fine but by itself does not paint the whole picture. The
theory does not take into account how genes on the Y chromosome can affect the
expression of other genes. For instance, a single gene on the Y chromosome can
affect the expression of thousands of other genes across the whole genome.

[1] Evolutionary Psychology: The New Science of the Mind (4th Edition) by
David Buss, pages 101-102

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lngnmn
Exposure to various environmental factors.

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PepeGomez
They have more iron in their bodies.

~~~
da02
I agree. However, most of the info. I've read comes from "health journalist"
Bill Sardi. Despite the sound ideas, he is still brushed off as a crack-pot.
Nevertheless, I'm betting on the "over-mineralization" theory of aging.

I doubt it will ever become accepted. People seem to like to think in terms of
genetics (because that's what the "experts" talk about most of the time) and
"hi-tech" dreams (e.g.nano-bots killing off cancer). Even when epigenetics is
mentioned, they still get it wrong when applied to age-related illnesses.

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ChickeNES
Bil Sardi is brushed off as a crackpot because he is a crackpot.

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PepeGomez
Why? It seems to be the only theory that actually fits the evidence, unlike
SENS and similar nonsense.

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satchel
Shows just how much change can come from genetic tech. Nature's source code.

